0000000001306447
AUTHOR
Maria Manconi
Sorbitol-penetration enhancer containing vesicles loaded with baicalin for the protection and regeneration of skin injured by oxidative stress and UV radiation.
Abstract Aiming at improving the protective effects of baicalin on the skin, new highly-biocompatible penetration enhancer containing vesicles (PEVs) were developed by modifying the base formulation of transfersomes with sorbitol, thus obtaining sorbitol-PEVs. An extensive evaluation of the physico-chemical features of both transfersomes and sorbitol-PEVs was carried out. Transfersomes were mainly close-packed, multi-compartment vesicles, while sorbitol-PEVs appeared mostly as single, spherical, unilamellar vesicles. All the vesicles were small in size (∼128 nm) and negatively charged (∼−67 mV), without significant differences between the formulations. The in vitro delivery of baicalin to i…
Protective effect of grape extract phospholipid vesicles against oxidative stress skin damages
Abstract Grape extract rich in polyphenols (∼129 ± 32 mg of gallic acid equivalents per g of dry extract) was obtained from the pomaces of Cannonau grapes by homogenization in an ethanol/water mixture. The efficacy of ultrasounds in speeding up the extraction kinetics of polyphenols was demonstrated. The extract was incorporated in liposomes and PEVs (penetration enhancer containing vesicles) with Labrasol ® or Labrasol ® /ethanol. All the vesicles were spherical and predominantly unilamellar: liposomes were large (∼927 nm) and polydispersed (PI ∼0.56), while PEVs were small (∼140 nm) and fairly homogeneous (PI ∼0.3). Moreover, PEVs were able to incorporate a high amount of the extract (∼98…
Composite soy lecithin–decylpolyglucoside vesicles: A theoretical and experimental study
In the present work, vesicles made with soy lecithin and a commercial mixture of alkyl polyglucosides were prepared and characterized. Vesicles with a constant amount of soy lecithin and an increasing amount of a decylpolyglucoside surfactant, (OrNS10), were formulated and their physicochemical properties were studied with the aim to design a drug delivery system suitable for different applications. To this purpose, morphology, size distribution, ζ-potential and apparent viscosity of the prepared vesicles were studied. Vesicles were also characterized by using optical and light polarized microscopy, transmission electron microscopy and photon correlation spectroscopy. A stability study was …
Advanced strategy to exploit wine-making waste by manufacturing antioxidant and prebiotic fibre-enriched vesicles for intestinal health.
Grape extract-loaded fibre-enriched vesicles, nutriosomes, were prepared by combining antioxidant extracts obtained from grape pomaces and a prebiotic, soluble fibre (Nutriose®FM06). The nutriosomes were small in size (from ∼140 to 260 nm), homogeneous (polydispersity index < 0.2) and highly negative (∼ −79 mV). The vesicles were highly stable during 12 months of storage at 25 °C. When diluted with warmed (37 °C) acidic medium (pH 1.2) of high ionic strength, the vesicles only displayed an increase of the mean diameter and a low release of the extract, which were dependent on Nutriose concentration. The formulations were highly biocompatible and able to protect intestinal cells (Caco-2) fro…
Nutriosomes: Prebiotic delivery systems combining phospholipids, a soluble dextrin and curcumin to counteract intestinal oxidative stress and inflammation
Nutriosomes, new phospholipid nanovesicles specifically designed for intestinal protection were developed by simultaneously loading a water-soluble dextrin (Nutriose® FM06) and a natural antioxidant (curcumin). Nutriosomes were easily fabricated in a one-step, organic solvent-free procedure. The stability and delivery performances of the vesicles were improved by adding hydroxypropyl methylcellulose. All the vesicles were small in size (mean diameter ∼168 nm), negatively charged (zeta potential ∼-38 mV, irrespective of their composition), and self-assembled predominantly in unilamellar vesicles stabilized by the presence of Nutriose®, which was located in both the inter-lamellar and inter-v…
Mangiferin glycethosomes as a new potential adjuvant for the treatment of psoriasis
[EN] Mangiferin, a natural compound isolated from Mangifera indica L, was incorporated in glycerosomes, ethosomes and alternatively in glycerol-ethanol phospholipid vesicles (glycethosomes). Actually, only glycethosomes were able to stably incorporate the mangiferin that was loaded at increasing concentrations (2, 4, 6, 8 mg/mL). The morphology, size distribution, rheological properties, surface charge and entrapment efficiency of prepared vesicles were deeply measured. All vesicles were mainly spherical, oligolamellar, small in size (similar to 145 nm) and negatively charged (similar to-40 mV), as confirmed by cryo-TEM observation and dynamic laser light scattering measurements. The higher…
Bifunctional viscous nanovesicles co-loaded with resveratrol and gallic acid for skin protection against microbial and oxidative injuries.
Resveratrol and gallic acid were co-loaded in phospholipid vesicles aiming at protecting the skin from external injuries, such as oxidative stress and microbial infections. Liposomes were prepared using biocompatible phospholipids dispersed in water. To improve vesicle stability and applicability, the phospholipids and the phenols were dispersed in water/propylene glycol or water/glycerol, thus obtaining PEVs and glycerosomes, respectively. The vesicles were characterized by size, morphology, physical stability, and their therapeutic efficacy was investigated in vitro. The vesicles were spherical, unilamellar and small in size: liposomes and glycerosomes were around 70nm in diameter, while …
From waste to health: sustainable exploitation of grape pomace seed extract to manufacture antioxidant, regenerative and prebiotic nanovesicles within circular economy
AbstractPomace seed extract loaded vesicles were prepared as promising technological and green solution to exploit agri-food wastes and by-products, and develop high value-added products for human health. An antioxidant extract rich in bioactive compounds (epicatechins, catechin, gallic acid, quercetin and procynidins) was obtained from the seeds isolated from the pomace of Cannonau red grape cultivar. The extract was incorporated into phospholipid vesicles ad hoc formulated for intestinal delivery, by combining them, for the first time, whit a maltodextrin (Glucidex). Glucidex-transfersomes, glucidex-hyalurosomes and glucidex-hyalutransferomes were prepared, characterized and tested. Gluci…
Exploring the co-loading of lidocaine chemical forms in surfactant/phospholipid vesicles for improved skin delivery
Abstract Objectives The present study was aimed at targeting the skin to deliver lidocaine loaded in surfactant/phospholipid vesicles tailored for improved local delivery. The influence of different formulation parameters was explored to maximise drug efficacy. Methods The vesicles were prepared using a mixture of soy lipids (Phospholipon 50) and a surfactant with penetration-enhancing properties (Oramix CG110, Labrasol, Labrafac PG or Labrafac CC), and loaded with lidocaine. The formulations were analysed in detail by cryo-TEM, SAXS, Turbiscan Lab, and tested in permeation experiments through new born pig skin, as a function of the chemical form and concentration of lidocaine (i.e. free ba…
Theoretical and experimental evaluation of decypolyglucoside vesicles as potential drug delivery systems
The aim of this work was to ascertain the capability of a commercial mixture of decylpolyglucoside (Orami.x NS10) to form vesicle structures in water, either alone or in association with cholesterol. To this purpose, we compared results obtained from a theoretical model with those acquired from the experimental characterization of different Orami.x NS10/cliolesterol mixtures. The germen vesicular formation theory was used to predict the formation process of vesicular structures. To this purpose, the energy balance involved in the vesicle formation was calculated using critical concentration for vesicle formation (ccf), surface tension and molecular area of decylpolyglucoside. The ccf was me…
Fabrication of quercetin and curcumin bionanovesicles for the prevention and rapid regeneration of full-thickness skin defects on mice
In the present work biocompatible quercetin and curcumin nanovesicles were developed as a novel approach to prevent and restore skin tissue defects on chronic cutaneous pathologies. Stable and suitable quercetin- and curcumin-loaded phospholipid vesicles, namely liposomes and penetration enhancer-containing vesicles (PEVs), were prepared. Vesicles were made from a highly biocompatible mixture of phospholipids and alternatively a natural polyphenol, quercetin or curcumin. Liposomes were obtained by adding water, while PEVs by adding polyethylene glycol 400 and Oramix®CG110 to the water phase. Transmission electron microscopy, cryogenic-transmission electron microscopy and small- and wide-ang…
Nanotechnology for Natural Medicine: Formulation of Neem Oil Loaded Phospholipid Vesicles Modified with Argan Oil as a Strategy to Protect the Skin from Oxidative Stress and Promote Wound Healing
Neem oil, a plant-derived product rich in bioactives, has been incorporated in liposomes and hyalurosomes modified by adding argan oil and so called argan-liposomes and argan-hyaluro-somes. Argan oil has also been added to the vesicles because of its regenerative and protective effects on skin. In the light of this, vesicles were specifically tailored to protect the skin from oxidative stress and treat lesions. Argan-liposomes were the smallest vesicles (~113 nm); the addition of sodium hyaluronate led to an increase in vesicle size (~143 nm) but it significantly improved vesicle stability during storage. In vitro studies confirmed the free radical scavenging activity of formula-tions, irre…
Nanoincorporation of curcumin in polymer-glycerosomes and evaluation of their in vitro–in vivo suitability as pulmonary delivery systems
The aim of this work was to deliver curcumin into the lungs by incorporating it into innovative vesicles obtained using phospholipids and high concentrations of glycerol (50%, v/v), so called glycerosomes, which were then combined with two polymers: sodium hyaluronate and trimethyl chitosan to form polymer-glycerosomes. These systems were prepared without the use of organic solvents or acidic solutions and their physico-chemical properties were fully characterized. Cryogenic transmission electron microscopy and small-angle X-ray scattering showed that both glycerosomes and polymer-glycerosomes were spherical, mainly unilamellar and of nanometric size (65–112 nm). The vesicles were readily n…
Functional response of novel bioprotective poloxamer-structured vesicles on inflamed skin
[EN] Resveratrol and gallic acid, a lipophilic and a hydrophilic phenol, were co-loaded in innovative, biocompatible nanovesicles conceived for ensuring the protection of the skin from oxidative-and inflammatory-related affections. The basic vesicles, liposomes and glycerosomes, were produced by a simple, one-step method involving the dispersion of phospholipid and phenols in water or water/glycerol blend, respectively. Liposomes and glycerosomes were modified by the addition of poloxamer, a stabilizer and viscosity enhancer, thus obtaining viscous or semisolid dispersions of structured vesicles. The vesicles were spherical, unilamellar and small in size (similar to 70 nm in diameter). The …
Freeze-dried eudragit-hyaluronan multicompartment liposomes to improve the intestinal bioavailability of curcumin.
This work aimed at finding an innovative vesicle-type formulation able to improve the bioavailability of curcumin upon oral administration. To this purpose, phospholipid, Eudragit® S100 and hyaluronan sodium salt were combined to obtain eudragit-hyaluronan immobilized vesicles using an easy and environmentally-friendly method. For the first time, the two polymers were combined in a system intended for oral delivery, to enhance curcumin stability when facing the harsh environment of the gastrointestinal tract. Four different formulations were prepared, keeping constant the amount of the phospholipid and varying the eudragit-hyaluronan ratio. The freeze-drying of the samples, performed to inc…
COMBINATION OF ARGAN OIL AND PHOSPHOLIPIDS FOR THE DEVELOPMENT OF AN EFFECTIVE LIPOSOME-LIKE FORMULATION ABLE TO IMPROVE SKIN HYDRATION AND ALLANTOIN DERMAL DELIVERY
Allantoin is traditionally employed in the treatment of skin ulcers and hypertrophic scars. In the present work, to improve its local deposition in the skin and deeper tissues, allantoin was incorporated in conventional liposomes and in new argan oil enriched liposomes. In both cases, obtained vesicles were unilamellar, as confirmed by cryo-TEM observation, but the addition of argan oil allowed a slight increase of the mean diameter (∼130nm versus ∼85nm). The formulations, especially those containing argan oil, favoured the allantoin accumulation in the skin, in particular in the dermis (∼8.7μg/cm(2)), and its permeation through the skin (∼33μg/cm(2)). The performances of vesicles as skin d…
Inhibition of skin inflammation by baicalin ultradeformable vesicles.
The topical efficacy of baicalin, a natural flavonoid isolated from Scutellaria baicalensis Georgi, which has several beneficial properties, such as antioxidative, antiviral, anti-inflammatory and antiproliferative, is hindered by its poor aqueous solubility and low skin permeability. Therefore, its incorporation into appropriate phospholipid vesicles could be a useful tool to improve its local activity. To this purpose, baicalin at increasing concentrations up to saturation, was incorporated in ultradeformable vesicles, which were small in size (∼67nm), monodispersed (PI<0.19) and biocompatible, regardless of the concentration of baicalin, as confirmed by in vitro studies using fibroblasts…
Formulation of liposomes loading lentisk oil to ameliorate topical delivery, attenuate oxidative stress damage and improve cell migration in scratch assay
[EN] Pistacia lentiscus L. is a sclerophyllous shrub capable of growing under harsh climatic conditions especially in the Mediterranean Basin. Different products can be obtained from this plant, such as essential oil, mastic gum or even fixed oil. The last is well known for its flavor which is mainly exploited in the food industry. Additionally, it has been traditionally used in the treatment of skin diseases, but, at the moment, any suitable formulation for skin delivery has been formulated and its biological effects was not deeply confirmed. Given that, in the present study, the lentisk oil has been formulated in liposomes at different concentrations (10, 20, 30 mg/ml) and their physicoch…
Effect of several electrolytes on the rheopectic behaviour of concentrated soy lecithin dispersions
Abstract Concentrated dispersions of soy lecithin (60 g/L) prepared by sonication-freezing–unfreezing method show a non-newtonian behaviour and a significant rheopexy. Shear stress versus shear rate plots shows a loop hysteresis area, which have been studied in soy lecithin dispersions prepared with aqueous solutions of various electrolytes (NaCl, CaCl2, MgCl2 and AlCl3) with concentrations in the range 10−5 to 10−2 mol/L. Also we have studied the effect of different pH on soy lecithin dispersions. The results have revealed a very sensitive influence of nature, valence and concentration of the respective cations and the pH value on the loop hysteresis area values. It seems to indicate that …
Baicalin and berberine ultradeformable vesicles as potential adjuvant in vitiligo therapy.
0.5-1% of the world's population is affected by vitiligo, a disease characterized by a gradual depigmentation of the skin. Baicalin and berberine are natural compounds with beneficial activities, such as antioxidant, anti-inflammatory and proliferative effects. These polyphenols could be useful for the treatment of vitiligo symptoms, and their efficacy can be improved by loading in suitable carriers. The aim of this work was to formulate and characterize baicalin or berberine loaded ultradeformable vesicles, and demonstrate their potential as adjuvants in the treatment of vitiligo. The vesicles were produced using a previously reported simple, scalable method. Their morphology, size distrib…
Nanodesign of new self-assembling core-shell gellan-transfersomes loading baicalin and in vivo evaluation of repair response in skin
Gellan nanohydrogel and phospholipid vesicles were combined to incorporate baicalin in new self-assembling core-shell gellan-transfersomes obtained by an easy, scalable method. The vesicles were small in size (~107 nm) and monodispersed (P.I. ≤ 0.24), forming a viscous system (~24 mPa/s) as compared to transfersomes (~1.6 mPa/s), as confirmed by rheological studies. Gellan was anchored to the bilayer domains through cholesterol, and the polymer chains were distributed onto the outer surface of the bilayer, thus forming a core-shell structure, as suggested by SAXS analyses. The optimal carrier ability of core-shell gellan-transfersomes was established by the high deposition of baicalin in th…
Eco-scalable baicalin loaded vesicles developed by combining phospholipid with ethanol, glycerol, and propylene glycol to enhance skin permeation and protection.
Abstract A new class of biocompatible and scalable phospholipid vesicles was developed, aiming at improving the efficacy of baicalin on the skin. Phosphatidylcholine and baicalin (a natural polyphenol) were hydrated in two steps with a mixture of ethanol, glycerol, and propylene glycol at different ratios, and a low amount of water (4%). Hence, water was almost completely replaced by the co-solvents, which were never used before as predominant dispersing medium of phospholipid vesicles. The vesicles appeared three-dimensionally structured, forming a network that conferred a high viscosity to the dispersions. The vesicles were unilamellar, small in size (∼100 nm), and stable during 12 months…
Composition influence on pulmonary delivery of rifampicin liposomes.
The effects of lipid concentration and composition on the physicochemical properties, aerosol performance and in vitro toxicity activity of several rifampicin-loaded liposomes were investigated. To this purpose, six liposome formulations containing different amounts of soy phosphatidylcholine and hydrogenated soy phosphatidylcholine, with and without cholesterol and oleic acid, were prepared and fully characterized. Uni- or oligo-lamellar, small (&#126;100 nm), negatively charged (&#126;60 mV) vesicles were obtained. Lipid composition affected aerosol delivery features of liposomal rifampicin; in particular, the highest phospholipid concentration led to a better packing of the vesic…
Extraction, Characterization and Incorporation of Hypericum scruglii Extract in Ad Hoc Formulated Phospholipid Vesicles Designed for the Treatment of Skin Diseases Connected with Oxidative Stress
An extract of Hypericum scruglii, an endangered endemic plant of Sardinia (Italy), was prepared and characterized. It was loaded in special phospholipid vesicles, glycerosomes, which were modified by adding maltodextrin (glucidex) and a polymer (gelatin or hyaluronan). The corresponding liposomes were also prepared and used as reference. The vesicles disclosed suitable physicochemical features for skin delivery. Indeed, their mean diameter ranged from 120 to 160 nm, they were homogeneously dispersed (polydispersity index &le
Topical anti-inflammatory potential of quercetin in lipid-based nanosystems: In vivo and in vitro evaluation
Purpose: To develop quercetin-loaded phospholipid vesicles, namely liposomes and PEVs (Penetration Enhancer-containing Vesicles), and to investigate their efficacy on TPA-induced skin inflammation. Methods: Vesicles were made from a mixture of phospholipids, quercetin and polyethylene glycol 400 (PEG), specifically added to increase drug solubility and penetration through the skin. Vesicle morphology and self-assembly were probed by Cryo-Transmission Electron Microscopy and Small/Wide Angle X-ray Scattering, as well as the main physico-chemical features by Light Scattering. The anti-inflammatory efficacy of quercetin nanovesicles was assessed in vivo on TPA-treated mice dorsal skin by the d…
Faceted phospholipid vesicles tailored for the delivery of Santolina insularis essential oil to the skin
The aim of this work was to formulate Santolina insularis essential oil-loaded nanocarriers, namely Penetration Enhancer containing Vesicles (PEVs), evaluate the physico-chemical features and stability, and gain insights into their ability to deliver the oil to the skin.S. insularis essential oil was obtained by steam distillation, and was predominantly composed of terpenes, the most abundant being β-phellandrene (22.6%), myrcene (11.4%) and curcumenes (12.1%). Vesicles were prepared using phosphatidylcholine, and ethylene or propylene glycol were added to the water phase (10% (v/v)) to improve vesicle performances as delivery systems. Vesicles were deeply characterized by light scattering,…
Chitosomes as drug delivery systems for C-phycocyanin: preparation and characterization.
The aim of this work was to investigate chitosomes, i.e. liposomes coated by a polyelectrolyte complex between chitosan (CH) and xantan gum (XG), as potential delivery system for oral administration of the protein C-phycocyanin. To this purpose several CH-XG-microcomplexes were prepared in aqueous lactic acid at different chitosan-xanthan gum percent ratios and rheological properties of the microcomplexes were studied to analyse the contribution of chitosan and xanthan gum in the reaction of microcomplexation. After establishing the best microcomplexes, chitosomes were prepared by coating C-phycocyanin loaded liposomes with the CH-XG hydrogels using spray-drying or freeze-drying. The chitos…
Inhibition of skin inflammation in mice by diclofenac in vesicular carriers: Liposomes, ethosomes and PEVs
Diclofenac-loaded phospholipid vesicles, namely conventional liposomes, ethosomes and PEVs (penetration enhancer-containing vesicles) were developed and their efficacy in TPA (phorbol ester) induced skin inflammation was examined. Vesicles were made from a cheap and unpurified mixture of phospholipids and diclofenac sodium; Transcutol P and propylene glycol were added to obtain PEVs, and ethanol to produce ethosomes. The structure and lamellar organization of the vesicle bilayer were investigated by transmission electron microscopy and small and wide angle X-ray scattering, as well as the main physico-chemical features. The formulations, along with a diclofenac solution and commercial Volta…
Glycerosomes: Use of hydrogenated soy phosphatidylcholine mixture and its effect on vesicle features and diclofenac skin penetration.
In this work, diclofenac was encapsulated, as sodium salt, in glycerosomes containing 10, 20 or 30% of glycerol in the water phase with the aim to ameliorate its topical efficacy. Taking into account previous findings, glycerosome formulation was modified, in terms of economic suitability, using a cheap and commercially available mixture of hydrogenated soy phosphatidylcholine (P90H). P90H glycerosomes were spherical and multilamellar; photon correlation spectroscopy showed that obtained vesicles were ∼131nm, slightly larger and more polydispersed than those made with dipalmitoylphosphatidylcholine (DPPC) but, surprisingly, they were able to ameliorate the local delivery of diclofenac, whic…
Co-Loading of Ascorbic Acid and Tocopherol in Eudragit-Nutriosomes to Counteract Intestinal Oxidative Stress
The present study aimed at developing a new vesicular formulation capable of promoting the protective effect of ascorbic acid and tocopherol against intestinal oxidative stress damage, and their efficacy in intestinal wound healing upon oral administration. A pH-dependent copolymer (Eudragit®
Development and characterization of liposomes containing glycols as carriers for diclofenac
® Propylene glycol Permeation enhancer vesicles abstract This paper focuses on the preparation and characterization of new, stable phospholipid formulations as carriers for dermal delivery of diclofenac (DCF). To prepare these vesicles two water miscible permeation enhancers (PE) with glycol group: diethyleneglycol monoethyl ether (Transcutol ® , Trc) and propylene glycol (PG), were added at different concentrations (10%, 20%, 30%, 40%, 50%) during the preparation of diclofenac loaded soy lecithin (SL) liposomes. We added Transcutol ® or propylene glycol to the hydrophilic phase in order to obtain new systems able to enhance the skin delivery of diclofenac thanks to the synergic effect of g…
N-Succinyl-chitosan systems for 5-aminosalicylic acid colon delivery: In vivo study with TNBS-induced colitis model in rats
5-Aminosalicylic acid (5-ASA) loaded N-Succinyl-chitosan (SucCH) microparticle and freeze-dried system were prepared as potential delivery systems to the colon. Physicochemical characterization and in vitro release and swelling studies were previously assessed and showed that the two formulations appeared to be good candidates to deliver the drug to the colon. In this work the effectiveness of these two systems in the treatment of inflammatory bowel disease was evaluated. In vitro mucoadhesive studies showed excellent mucoadhesive properties of both the systems to the inflamed colonic mucosa. Experimental colitis was induced by rectal instillation of 2,4,6-trinitrobenzene sulfonic acid (TNB…
Glycerosomes:investigation of role of 1,2-dimyristoyl-sn-glycero-3-phosphatidycholine (DMPC) on the assembling and skin delivery performances
Glycerosomes were formulated using 1,2-dimyristoyl-sn-glycero-3-phosphatidycholine (DMPC), diclofenac sodium salt and 10, 20 or 30% glycerol in the water phase, while corresponding liposomes were prepared with the same amount of DMPC and diclofenac, without glycerol. The aim of the present work was to evaluate the effect of the used phospholipid on vesicle features and ability to favour diclofenac skin deposition by comparing these results with those found in previous works performed using hydrogenated soy phosphatidylcholine (P90H) and dipalmitoylphosphatidylcholine (DPPC). Liposomes and glycerosomes were multilamellar, liposomes being smaller (72±6nm). Interactions among glycerol, phospho…
Transcutol containing vesicles for topical delivery of minoxidil
The aim of this work was to evaluate the ability of Transcutol (Trc) to produce elastic vesicles with soy lecithin (SL) and study the influence of the obtained vesicles on in vitro (trans)dermal delivery of minoxidil. To this purpose, so-called penetration enhancer-containing vesicles (PEVs) were prepared using Trc aqueous solutions (5-10-20-30% v/v) as hydrophilic phase. SL liposomes, without Trc, were used as control. Prepared formulations were characterized in terms of size distribution, morphology, zeta potential, deformability, and rheological behavior. The influence of the obtained PEVs on (trans)dermal delivery of minoxidil was studied by in vitro diffusion experiments through pig sk…
Comparison between Citral and Pompia Essential Oil Loaded in Phospholipid Vesicles for the Treatment of Skin and Mucosal Infections
Citrus species extracts are well known sources of bio-functional compounds with health-promoting effects. In particular, essential oils are known for their antibacterial activity due to the high content of terpenes. In this work, the steam-distilled essential oil from the leaves of Citrus limon var. pompia was loaded in phospholipid vesicles. The physico-chemical characteristics of the essential oil loaded vesicles were compared with those of vesicles that were loaded with citral, which is one of the most abundant terpenes of Citrus essential oils. The biocompatibility of the vesicles was assessed in vitro in human keratinocytes. Furthermore, the antimicrobial activity of the vesicles was t…
Thymus essential oil extraction, characterization and incorporation in phospholipid vesicles for the antioxidant/antibacterial treatment of oral cavity diseases
The aim of the work was to extract, characterize, and formulate Thymus capitatus (Tymbra capitata) essential oil in phospholipid vesicles: liposomes, glycerosomes and Penetration Enhancer-containing Vesicles (PEVs). The steam-distilled essential oil was mainly composed of carvacrol. The oil was mixed with lecithin and water to produce liposomes, or different ratios of water/glycerol or water/propylene glycol (PG) to produce glycerosomes and PG-PEVs, respectively. Cryo-TEM showed the formation of unilamellar, spherical vesicles, and light scattering disclosed that their size increased in the presence of glycerol or PG, which improved long-term stability. The formulations were highly biocompa…
Penetration enhancer containing vesicles as carriers for dermal delivery of tretinoin.
The ability of a recently developed novel class of liposomes to promote dermal delivery of tretinoin (TRA) was evaluated. New penetration enhancer-containing vesicles (PEVs) were prepared adding to conventional phosphatidylcholine vesicles (control liposomes) different hydrophilic penetration enhancers: Oramix® NS10 (OrNS10), Labrasol® (Lab), Transcutol® P (Trc), and propylene glycol (PG). Vesicles were characterized by morphology, size distribution, zeta potential, incorporation efficiency, stability, rheological behaviour, and deformability. Small, negatively charged, non-deformable, multilamellar vesicles were obtained. Rheological studies showed that PEVs had fluidity higher than conven…
Design, characterization and in vitro evaluation of 5-aminosalicylic acid loaded N-succinyl-chitosan microparticles for colon specific delivery
The objective of this study was to prepare NS-chitosan microparticles for the delivery of 5-aminosalicylic acid (5-ASA) to the colon. Microparticles can spread out over a large area of colon allowing a more effective local efficacy of 5-ASA. N-Succinyl-chitosan was chosen as carrier system because of its excellent pharmaceutical properties in colon drug targeting such as poor solubility in acid environment, biocompatibility, mucoadhesive properties, and low toxicity. It was prepared by introducing succinic group into chitosan N-terminals of the glucosamine units. 5-ASA loaded NS-chitosan microparticles were prepared using spray-drying. As a control, a matrix obtained by freeze-drying techni…
Phytocomplexes extracted from grape seeds and stalks delivered in phospholipid vesicles tailored for the treatment of skin damages
Abstract In the present work, red grape seed and stalk extracts were incorporated in vesicular systems designed for topical application. The phytocomplexes were obtained by maceration of biomasses in ethanol and subsequent lyophilisation. Seed extract was rich in catechin, epicatechin, epicatechin gallate, while gallic acid, epigallocatechin gallate, quercetin, quercetin 3-glucoside and malvidin-3-glucoside were detected in higher amounts in the stalk extract. Both extracts were incorporated in liposomes, hyalurosomes and transfersomes. In addition, hyalo-transfersomes were developed for the first time in this work, by combining the main modifiers of hyalurosomes and transfersomes (i.e., so…
Delivery of liquorice extract by liposomes and hyalurosomes to protect the skin against oxidative stress injuries.
Liquorice extract, obtained by percolation in ethanol of Glycyrrhiza glabra L. roots, was incorporated in liposomes and hyalurosomes, new phospholipid-sodium hyaluronate vesicles, and their protective effect against oxidative stress skin damages was probed. As a comparison, raw glycyrrhizin was also tested. All the vesicles were small in size (≤ 100 nm), with a highly negative zeta potential ensuring long-term stability, and able to incorporate a high amount of the extract. In vitro tests showed that the liquorice extract loaded in vesicles was able to scavenge DPPH free radical (80% inhibition) and to protect 3T3 fibroblasts against H2O2-induced oxidative stress, restoring the normal condi…
Entrapment of Citrus limon var. pompia Essential Oil or Pure Citral in Liposomes Tailored as Mouthwash for the Treatment of Oral Cavity Diseases
This work aimed at developing a mouthwash based on liposomes loading Citrus limon var. pompia essential oil or citral to treat oropharyngeal diseases. Vesicles were prepared by dispersing phosphatidylcholine and pompia essential oil or citral at increasing amounts (12, 25 and 50 mg/mL) in water. Transparent vesicle dispersions were obtained by direct sonication avoiding the use of organic solvents. Cryogenic transmission electron microscopy (cryo-TEM) confirmed the formation of unilamellar, spherical and regularly shaped vesicles. Essential oil and citral loaded liposomes were small in size (~110 and ~100 nm, respectively) and negatively charged. Liposomes, especially those loading citral, …
Development of novel diolein–niosomes for cutaneous delivery of tretinoin: Influence of formulation and in vitro assessment
Abstract This work describes innovative niosomes, composed of diolein alone or in association with the hydrophilic penetration enhancer Labrasol ® , as carriers for cutaneous drug delivery. The model drug was tretinoin and conventional, and Labrasol ® containing liposomes was used as controls to evaluate the influence of vesicle composition and the role of Labrasol ® on vesicle physico-chemical properties and performance as skin delivery system. Vesicles, prepared by the thin film hydration technique, were characterized in terms of size distribution, morphology, zeta potential, structure, incorporation efficiency, and rheological properties. The influence of carrier composition on tretinoin…
Oleuropein multicompartment nanovesicles enriched with collagen as a natural strategy for the treatment of skin wounds connected with oxidative stress.
Aim: Collagen-enriched transfersomes, glycerosomes and glytransfersomes were specifically tailored for skin delivery of oleuropein. Methods: Vesicles were prepared by direct sonication and their main physicochemical and technological properties were measured. Biocompatibility, protective effect and promotion of the healing of a wounded cell monolayer were tested in vitro using fibroblasts. Results: Vesicles were mainly multicompartment, small (∼108 nm), slightly polydispersed (approximately 0.27) and negatively charged (~-49 mV). Oleuropein was incorporated in high amounts (approximately 87%) and vesicles were stable during four months of storage. In vitro studies confirmed the low toxicit…
Inhalable polymer-glycerosomes as safe and effective carriers for rifampicin delivery to the lungs
Rifampicin loaded glycerosomes, vesicles composed of phospholipids, glycerol and water, were combined with trimethyl chitosan chloride (TMC) to prepare TMC-glycerosomes or, alternatively, with sodium hyaluronate (HY) to obtain HY-glycerosomes. These new hybrid nanovesicles were tested as carriers for pulmonary delivery of rifampicin. Glycerosomes without polymers were also prepared and characterized. All vesicles were similar: they were spherical, multilamellar and able to incorporate good amount of rifampicin (EE%∼55%). The addition of the polymers to the formulations allowed an increase of mean diameter. All the glycerosomes, in particular HY-glycerosomes, were able to deliver the drug to…
Viscoelastic properties of concentrated dispersions in water of soy lecithin
Abstract Viscoelastic properties of soy lecithin dispersions at 60, 120, 180 and 240 g l−1 in water have been studied as a function of ionic strength (NaCl concentrations in the range 10−5–10−2 mol l−1) and of preparation method (sonication, freezing–unfreezing). Viscosity measurements of sonicated dispersions in a rotatory viscometer show Newtonian and plastic (Bingham) behavior, whereas the frozen–unfrozen dispersions show a spectacular change in their viscoelastic properties, that is, a non-Newtonian behavior with pseudoplastic characteristics and rheopexy. These properties have been related to electrokinetic characteristics of the segregated vesicles in each case. A decrease in ζ-potent…
Innovative strategies to treat skin wounds with mangiferin: fabrication of transferosomes modified with glycols and mucin
Aim: The moisturizing properties of glycerol, the penetration enhancing capability of propylene glycol and the bioadhesive properties of mucin were combined to improve the carrier capabilities of transfersomes and the efficacy of mangiferin in the treatment of skin lesions. Materials & methods: Mangiferin was incorporated in transfersomes and glycoltransfersomes, which were also modified with mucin. The physico–chemical features were assessed, along with the efficacy against oxidative stress and skin wounds in vitro and in vivo. Results: Glycoltransfersomes promoted the deposition of mangiferin in epidermis and dermis, protected fibroblasts from oxidative stress and stimulated their pr…
Development of curcumin loaded sodium hyaluronate immobilized vesicles (hyalurosomes) and their potential on skin inflammation and wound restoring.
In the present work new highly biocompatible nanovesicles were developed using polyanion sodium hyaluronate to form polymer immobilized vesicles, so called hyalurosomes. Curcumin, at high concentration was loaded into hyalurosomes and physico-chemical properties and in vitro/in vivo performances of the formulations were compared to those of liposomes having the same lipid and drug content. Vesicles were prepared by direct addition of dispersion containing the polysaccharide sodium hyaluronate and the polyphenol curcumin to a commercial mixture of soy phospholipids, thus avoiding the use of organic solvents. An extensive study was carried out on the physico-chemical features and properties o…
An approach to rheological and electrokinetic behaviour of lipidic vesicles covered with chitosan biopolymer
The rheological and electrokinetic properties of soybean lecithin vesicles prepared from concentrated soy lecithin dispersions (250 g/L) obtained by slow swelling under shear conditions and mixed with chitosan biopolymer solutions were studied. The rheological behaviour of lecithin-chitosan vesicles was determined by shear stress against shear rate measurements, as well as by the variation on the hysteresis loop area. The results were compared with the rheopectic behaviour of soy lecithin dispersions without chitosan. An important change on the rheological properties of the complex dispersion was observed, depicting in a thixotropic behaviour with a plastic character in the presence of chit…
Co-loading of finasteride and baicalin in phospholipid vesicles tailored for the treatment of hair disorders
[EN] Hair loss affects a large number of people worldwide and it has a negative impact on the quality of life. Despite the availability of different drugs for the treatment of hair disorders, therapeutic options are still limited and scarcely effective. An innovative strategy to improve the efficacy of alopecia treatment is presented in this work. Finasteride, the only oral synthetic drug approved by Unites States Federal Drug Administration, was loaded in phospholipid vesicles. In addition, baicalin was co-loaded as an adjuvant. Their effect on hair growth was evaluatedin vitroandin vivo. Liposomes, hyalurosomes, glycerosomes and glycerol-hyalurosomes were manufactured by using a simple me…
In vitro study of N-succinyl chitosan for targeted delivery of 5-aminosalicylic acid to colon
In vitro study on N-succinyl chitosan and chitosan (control) matrices for selective colon delivery of 5-aminosalicylic acid is described. Matrices containing β-cyclodextrin were also prepared. As shown by DSC analyses, the drug was successfully loaded into the matrices reaching up to 95% entrapment efficiency. Swelling and drug release were studied at pH 1.2, pH 7.4, and in a pH gradient medium to simulate the gastro-intestinal transit. Main result of this study was a higher capability of N-succinyl chitosan alone to better control drug release in the simulated gastro-intestinal transit: N-succinyl chitosan gave the lowest release in acid medium (≅15%) and the highest in alkaline environmen…
Thermodynamical aspects regarding the formation of self-assembly decylpolyglucoside structures
In this study, we used a generalized form of a recently reported parametrization based on the differential geometry and the thermodynamics of dispersed systems to ascertain the capability of decylpolyglucoside alone or in association with cholesterol to form vesicle structures (niosomes). The theoretical calculation of the energy balance involved in the vesicles formation was carried out using values of the critical concentration of formation (ccf), surface tension and the molar surface area of the non-ionic surfactant. Furthermore, in order to confirm the theoretical results found in this work, we prepared and characterized vesicles made with decylpolyglucoside and cholesterol. The vesicle…
Nanocarriers for antioxidant resveratrol: formulation approach, vesicle self-assembly and stability evaluation.
In this work we studied various nanoformulations of resveratrol in phospholipid vesicles. Conventional phophatidylcholine liposomes were prepared and characterized in parallel with PEVs (Penetration Enhancer-containing Vesicles) obtained by adding one of eight selected amphiphilic penetration enhancers (PEs; 0.2% w/v; HLB range 1-16) to the composition. All vesicles were around 100 nm, negatively charged (∼-30 mV) and able to incorporate resveratrol in good yields (>74%). The structure and the lamellar self-organization of the vesicles were investigated by Transmission Electron Microscopy (TEM) and Small and Wide Angle X-ray Scattering (SWAXS). These analyses showed that the lamellarity of …
Optimization of Innovative Three-Dimensionally-Structured Hybrid Vesicles to Improve the Cutaneous Delivery of Clotrimazole for the Treatment of Topical Candidiasis
New three-dimensionally-structured hybrid phospholipid vesicles, able to load clotrimazole in a high amount (10 mg/mL), were obtained for the first time in this work by significantly reducing the amount of water (&le
Fabrication of polyelectrolyte multilayered vesicles as inhalable dry powder for lung administration of rifampicin
A polyelectrolyte complex based on chitosan and carrageenan was used to coat rifampicin-loaded vesicles and obtain a dry powder for inhalation by spray-drying. The polymer complexation on vesicle surface stabilized them and improved their adhesion on airways and epithelia cells. Uncoated liposomes were small in size, negatively charged and able to incorporate large amounts of rifampicin (70%). Coated vesicles were still able to load adequate amounts of drug (∼70%) but the coating process produced larger particles (1 μm) that were positively charged and with a spherical shape. Aerosol performances, evaluated using the next-generation impactor, showed that coated vesicles reached the 50% of f…
NNM-2021-0197 Suppl. Data
Percentage of oleuropein released from the dispersion or vesicles during 96 hours. The mean values ± standard deviations (error bars) are reported (n=3). Symbol * indicates values statistically different from the other values at the same time.