In situ forming hydrogels of new amino hyaluronic acid/benzoyl-cysteine derivatives as potential scaffolds for cartilage regeneration
A new chemical strategy is described to link ethylenediamino (EDA) groups to primary hydroxyl groups of hyaluronic acid (HA) and the obtained derivatives have been characterized by 1H-NMR and 13C-NMR analyses. Such HA–EDA derivatives have been exploited to control the functionalization degree in benzoyl-cysteine (BC) groups, chosen as moieties able to allow both self-assembling in aqueous media and an oxidative crosslinking. In particular, the kinetics of oxidation of thiol groups in HA–EDA–BC derivatives has been studied in Dulbecco's Phosphate Buffer Solution (DPBS) pH 7.4 by colorimetric assays and rheological measurements. Mechanical properties of chemical hydrogels obtained after oxida…
Guar gum/borax hydrogel: Rheological, low field NMR and release characterizations
Guar gum (GG) and Guar gum/borax (GGb) hydrogels are studied by means of rheology, Low Field Nuclear Magnetic Resonance (LF NMR) and model drug release tests. These three approaches are used to estimate the mesh size (ζ) of the polymeric network. A comparison with similar Scleroglucan systems is carried out. In the case of GGb, the rheological and Low Field NMR estimations of ζ lead to comparable results, while the drug release approach seems to underestimate ζ. Such discrepancy is attributed to the viscous effect of some polymeric chains that, although bound to the network to one end, can freely fluctuate among meshes. The viscous drag exerted by these chains slows down drug…
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…
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…
Mechanical Characterization of Polysaccharide/polyaminoacid Hydrogels as Potential Scaffolds for Tissue Regeneration
The mechanical properties of hydrogel scaffolds based on hyaluronic acid (HA) that were chemically crosslinked with α,β-poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-D,L-aspartamide (PHEA-EDA) were investigated. Variation of these properties as a function of three different PHEA-EDA amounts used to crosslink HA has been related to the reaction efficiency evaluated using a colorimetric assay. Moreover, the amount of unreacted amino groups that was still present in the hydrogels was related to the attachment behavior of human dermal fibroblasts to the hydrogel surface. The mechanical data and biological results suggest the suitability of the investigated hydrogels as scaffolds for the regener…
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…
Polyaspartamide-Doxorubicin Conjugate as Potential Prodrug for Anticancer Therapy
Purpose To synthesize a new polymeric prodrug based on ?,?- poly(N-2-hydroxyethyl)(2-aminoethylcarbamate)-d,l-aspartamide copolymer bearing amine groups in the side chain (PHEA-EDA), covalently linked to the anticancer drug doxorubicin and to test its potential application in anticancer therapy. Methods The drug was previously derivatized with a biocompatible and hydrophilic linker, leading to a doxorubicin derivative highly reactive with amino groups of PHEA-EDA. The PHEAEDA- DOXO prodrug was characterized in terms of chemical stability. The pharmacokinetics, biodistribution and cytotoxicity of the product was investigated in vitro and in vivo on human breast cancer MCF-7 and T47D cell lin…
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…
Long-Circulating Hyaluronan-Based Nanohydrogels as Carriers of Hydrophobic Drugs
[EN] Nanohydrogels based on natural polymers, such as polysaccharides, are gaining interest as vehicles for therapeutic agents, as they can modify the pharmacokinetics and pharmacodynamics of the carried drugs. In this work, hyaluronan-riboflavin nanohydrogels were tested in vivo in healthy rats highlighting their lack of toxicity, even at high doses, and their different biodistribution with respect to that of native hyaluronan. They were also exploited as carriers of a hydrophobic model drug, the anti-inflammatory piroxicam, that was physically embedded within the nanohydrogels by an autoclave treatment. The nanoformulation was tested by intravenous administration showing an improvement of…