N-valproyl-L-tryptophan for CNS-targeting: synthesis, characterization and efficacy in vitro studies of a new potential antiepileptic drug.

2010

A new aminoacidic derivative of valproic acid (VPA) has been synthesized and characterized by analytical and spectral data. The rationale for the preparation of such potential antiepileptic agent is based on the observation that chemical combination of the anticonvulsant pharmacophore, VPA with essential aminoacids could afford more effective and less toxic actives. The synthesis, characterization, physico-chemical parameters functional for crossing Blood Brain Barrier of N-valproyl-L-tryptophan (4) are reported. The Log D pH7.4 (0.3) indicates that (4) is adequate to cross biological membranes. Its chemical and enzymatic stability were assessed. The experiments indicate high stability of c…

Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features

2006

Abstract In transbuccal absorption a major limitation could be the low permeability of the mucosa which implies low drug bioavailability. The ability of naltrexone hydrochloride (NLX) to penetrate a resembling histologically human buccal mucosa was assessed and the occurrence of any histomorphological changes observed. We used reconstituted human oral (RHO) non-keratinised epithelium as mucosal section and a Transwell diffusion cells system as bicompartmental model. Buccal permeation was expressed in terms of drug flux ( J s ) and permeability coefficients ( K p ). Data were collected using both artificial and natural human saliva. The main finding was that RHO does not restrain NLX permeat…

ChemInform Abstract: Synthesis and in vitro Studies on a Potential Dopamine Prodrug.

2009

Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Condensation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is described. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log Papp (…

Evaluation of Galantamine transbuccal absorption by reconstituted human oral epithelium and porcine tissue as buccal mucosa models: Part I

2008

Over the last decade, interest in delivering drugs through buccal mucosa has increased. As a major limitation in buccal drug delivery could be the low permeability of the epithelium, the aim of this study was to evaluate the aptitude of galantamine, useful in Alzheimer's disease, to penetrate the buccal mucosa. The evaluation of the ability of galantamine to permeate through the buccal epithelium was investigated using two permeation models. Firstly, in vitro permeation experiments were carried out using reconstituted human oral non-keratinised epithelium and Transwell diffusion cells system. Results were validated by ex vivo experiments using porcine buccal mucosa as membrane and Franz typ…

New prospective in treatment of Parkinson's disease: Studies on permeation of ropinirole through buccal mucosa

2012

The aptitude of ropinirole to permeate the buccal tissue was tested using porcine mucosa mounted on Franz-type diffusion cells as ex vivo model. Drug permeation was also evaluated in presence of various penetration enhancers and in iontophoretic conditions. Ropinirole, widely used in treatment of motor fluctuations of Parkinson's disease, passes the buccal mucosa. Flux and permeability coefficient values suggested that the membrane does not appear a limiting step to the drug absorption. Nevertheless, an initial lag time is observed but the input rate can be modulated by permeation enhancement using limonene or by application of electric fields. Absorption improvement was accompanied by the …

Galantamine delivery on buccal mucosa: permeation enhancement and design of matrix tablets

2009

The most important feature in transbuccal drug delivery is the low drug passage through the buccal mucosa. In our previous work we demonstrated the aptitude of Galantamine to penetrate the buccal tissue. The collected data suggested that Galantamine passively crosses the membrane, but the calculated Js and Kp values showed that the drug amount that crosses the membrane wasn’t sufficient to assure blood therapeutic level. So, in this study, ex vivo permeation tests, using porcine buccal mucosa, were performed in presence of physical or chemical enhancers. No significant differences in penetration rate were observed using chemical enhancers as sodium dehydrocholate, EDTA disodium salt and tri…

Carbamazepine transbuccal delivery: the histo-morphological features of reconstituted human oral epithelium and buccal porcine mucosae in the transmu…

2009

Transbuccal drug delivery is an attractive way of administration since several well-known advantages are provided, especially with respect to peroral management. Carbamazepine (CBZ) is an anticonvulsant which is useful in controlling neuropathic pain, and it is currently administered by peroral route, although its absorption and bioavailability is limited due to various factors. The oral cavity could be an interesting site for transbuccal CBZ delivery due to two properties: slow administration of constant low drug doses and less dose-related side effects. However, in transbuccal absorption a major limitation could be the low permeability of the mucosa which results in low drug bioavailabil…

5-Fluorouracil Buccal Tablets for Locoregional Chemotherapy of Oral Squamous Cell Carcinoma: Formulation, Drug Release and Histological Effects on Re…

2010

5-Fluorouracil (5-FU) is currently used for treatment of oral squamous cell carcinoma (OSCC). 5-FU is given by i.v. although the systemic administration is associated with severe toxic effects and no topical formulations of 5-FU for buccal drug delivery have been reported. In this study we would report the development of buccal tablets suitable for direct application of low-doses of 5-FU on cancer lesions. The topical administration could be effective on tumor area while systemic undesired side effects are avoided. Preliminarily, the limited tendency of 5-FU to cross the buccal tissue was established using reconstituted human oral epithelium (RHOE, in vitro) and porcine buccal mucosa (ex vi…

Medium-term Culture of Normal Human Oral Mucosa: A Novel Three-dimensional Model to Study the Effectiveness of Drugs Administration

2012

Tissue-engineered oral mucosal equivalents have been developed for in vitro studies for a few years now. However, the usefulness of currently available models is still limited by many factors, mainly the lack of a physiological extracellular matrix (ECM) and the use of cell populations that do not reflect the properly differentiated cytotypes of the mucosa of the oral cavity. For this reason, we have developed a novel three-dimensional culture model reflecting the normal architecture of the human oral mucosa, with the main aim of creating a better in vitro model where to test cellular responses to drugs administration. This novel 3D cell culture model (3D outgrowth) was set up using an arti…

Buccal Delivery of Methimazole as an Alternative Means for Improvement of Drug Bioavailability: Permeation Studies and Matrix System Design

2012

The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (J(s) = 0.068 mg cm(-2) h(-1) and K(p) = 0.065 cm h(-1…

Ocular gelling microspheres: in vitro precorneal retention time and drug permeation through reconstituted corneal epithelium.

2008

Purpose: The model drug norfloxacin (NOR)was encapsulated into trehalose (TRH) and hydroxyethylcellulose(NAT) microspheres to obtain a novel gelling ophthalmic delivery system for prolonged release on corneal tissue. Methods: We assessed NOR release from microspheres, prepared by the emulsion-solvent evaporation method. A new in vitro tear turnover model, including inserts containing reconstituted human corneal epithelium (RHC), was designed to evaluate the TRH/NAT microspheres’ precorneal retention time. Bioadhesive properties of TRH/NAT microspheres were validated by using drug-loaded microspheres prepared with gelatine (GLT) commonly used as reference material in adhesion studies. Result…

Release of naltrexone on buccal mucosa: Permeation studies, histological aspects and matrix system design

2007

Transbuccal drug delivery has got several well-known advantages especially with respect to peroral way. Since a major limitation in buccal drug delivery could be the low permeability of the epithelium, the aptitude of NLX to penetrate the mucosal barrier was assessed. Ex vivo permeation across porcine buccal mucosa 800 microm thick was investigated using Franz type diffusion cells and compared with in vitro data previously obtained by reconstituted human oral epithelium 100 microm thick. Both fluxes (Js) and permeability coefficients (K(p)) are in accordance, using either buffer solution simulating saliva or natural human saliva. Permeation was evaluated also in presence of chemical enhance…

Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three- Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile …

2012

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal …

Potential dopamine prodrug-loaded liposomes: preparation, characterization and in vitro stability studies

2009

Formulazione di sistemi innovativi per la somministrazione di antitumorali per il trattamento del Carcinoma Orale Squamoso

2008

Tablets for buccal administration of carbamazepine: comparative behavior of PAA microspheres and matrices

2005

Medium-Term Culture of Primary Oral Squamous Cell Carcinoma in a Three-Dimensional Model: Effects on Cell Survival Following Topical 5-Fluororacile D…

2012

Since the activity of several conventional anticancer drugs is restricted by resistance mechanisms and dose-limiting side-effects, the design of formulations for local application on malignant lesions seems to be an efficient and promising drug delivery approach. In this study, the effect of locally applied 5-FU on cell death was evaluated both in a SCC4/HEK001 model and in a newly proposed 3D outgrowth model of oral squamous cell carcinoma (OSCC). Initially, the optimal drug dose was established by delivery of solutions containing different amounts of 5-FU. The solution containing 1% (w/v) of 5-FU resulted effective in inducing cell death with complete eradication of cell colonies. Buccal …

CNS-targeted valproic-aminoacid conjugate: preliminary studies on pharmacokinetic parameters and antiepileptic activity

2009

Formulation and kinetic studies on matrix tablets loaded with 5-Fluorouracil useful in oral cancer treatment

2007

Sintesi, caratterizzazione e studio della stabilità chimica ed enzimatica di nuovi profarmaci della dopamina

2004

Matrix system development, permeation studies and histological features for transbuccal delivery of Naltrexone

2007

Transmucosal delivery della Galantamina attraverso mucosa buccale ex vivo

2007

Aminoacidic derivatives as novel CNS-targeted neurotherapeutics

2012

Drug delivery to the CNS is subject to the permeability limitations imposed by the BBB that regulates movements of actives in and out of the brain. During the drug discovery phase a key aspect could be the selection of the compounds properties crucial for brain penetration. Novel CNS-targeted neurotherapeutics should possess the optimal characteristics that allow passive diffusion through the BBB via the transcellular route, or have the structural features necessary to serve as a substrate for one of the endogenous transport systems of the BBB. An attractive and rewarding chemistry-based strategy, employed to increase the CNS transport of poorly penetrating therapeutic agents, is the transi…

Buccal Delivery of Carbamazepine (CBZ): a New Scenario in Menagement of Trigeminal Neuralgia (TN)

2008

Buccal delivery of Methimazole as an alternative means to optimize drug bioavailability: permeation studies and matrix system design

2012

The aim of this study was to investigate the potential for systemic administration of Methimazole (MMI) through the buccal mucosa as an alternative route for drug delivery. Considering that the most important restriction in buccal drug delivery could be the low permeability of the mucosa, the ability of MMI to cross the mucosal barrier was assessed. Permeation of MMI through porcine buccal mucosa was investigated ex vivo using Franz type diffusion cells, buffer solution simulating saliva or natural human saliva as donor phase. The collected data suggested that buccal mucosa does not hinder MMI diffusion and the drug crosses the membrane (Js = 0.068 mg cm-2 h-1 and Kp = 0.065 cm h-1). Matrix…

Transbuccal delivery of methimazole: ex vivo permeation studies, histomorphological features and matrix system development

2008

5-Fluororacile-loaded matrix tablets for locoregional delivery: effects on a three-dimensional culture model of primary oral squamous cell carcinoma

2012

Buccal delivery as a new challenge for treatment of motor fluctuations in Parkinson's Disease

2011

Aloin loaded matrix tablets for topical treatment of oral cancer

2008

DOPAMINE PRO-DRUGS FOR CNS TARGETING: SYNTHESIS, CHARACTERIZATION AND HYDROLYSIS BY BRAIN ENZYMES.

2004

Trehalose/hydroxyethylcellulose ocular gelling microspheres.

2008

MEDIUM-TERM CULTURE OF THE NORMAL ORAL MUCOSA: A NOVEL THREE-DIMENSIONAL MODEL TO STUDY THE EFFECTIVENESS OF DRUGS ADMINISTRATION

2009

Transmucosal permeability model of 5-fluorouracil through porcine and reconstituted oral epithelium

2005

Progettazione e realizzazione di sistemi di rilascio programmato nella terapia delle ferite da ustione

2004

Loaded sulfamethoxazole/trimethoprim soft films for treatment of burn wounds.

2006

Buccal delivery in treatment of Alzheimer disease: enhancement of galantamine absorption

2009

AMINOACID PRO-DRUG TO SHUTTLE VALPROIC ACID INTO CNS

2007

Sintesi di un nuovo derivato dell’acido valproico ed effetti in un modello sperimentale di epilessia ippocampale nel ratto

2008

Trehalose stabilizing effects on L-DOPA aqueous solutions

2007

Ex vivo transbuccal delivery of carbamazepine across porcine mucosa

2006

Enteric Aloin loaded microparticles for treatment of colorectal cancer

2008

Galantamine permeation through buccal mucosa: studies on reconstituted human oral epithelium and porcine tissue

2008

Efficacy of 5-FU topically applied on a buccal mucosal model resembling human tissue. A new chance for OSCC chemotherapy.

2008

Synthesis and in vitro studies on a potential dopamine prodrug.

2008

Dopamine delivery to the central nervous system (CNS) undergoes the permeability limitations of blood-brain barrier (BBB) which is a selective interface that excludes most water-soluble molecules from entering the brain. Neutral amino acids permeate the BBB by specific transport systems. Conden- sation of dopamine with neutral amino acids could afford potential prodrugs able to interact with the BBB endogenous transporters and easily enter the brain. The synthesis and characterization of the dopamine derivative 2-amino-N-[2-(3,4-dihydroxy-phenyl)-ethyl]-3-phenyl-propionamide (7) is de- scribed. The chemical and enzymatic stability of 7 was evaluated. The molecular weight (300 Da) and Log P …

Optimization of local delivery of antifungal agents in the oral cavity by a new formulation

2012

In recent years, with the increased use of antibiotics and immunosuppres-sive agents, there was an increased incidence of oral mycosis and Candida albicans is the most common etiologic agent in oropharyngeal candidiasis, especially in patients with HIV. The aim of this work is to develop a new dosage form containing miconazole (MN) to be topically applied on oral mucosa, allowing for a massive penetration of the drug in the tissue. The vehicle for the drug delivery was lipid microparticles incorporated in a hydrophilic gel. The lipospheres were obtained by hot melt encapsulation method using as matrix ingredients a mixtures of esters of fatty acids with higher fatty alcohols, having low mel…

Transbuccal delivery of l-dopa methyl ester: ex vivo permeation studies

2012