Crosslinked Poly(Methyl Vinyl Ether-Co-Maleic Anhydride) as Topical Vehicles for Hydrophilic and Lipophilic Drugs

Poly(methyl vinyl ether-co-maleic anhydride) crosslinked with ethylene glycol (GZ-ET), 1,4-butanediol (GZ-BUT), 1,6-exandiol (GZ-EX), 1,8-octanediol (GZ-OCT), 1,10-decanediol (GZ-DEC) or 1,12-dodecanediol (GZ-DOD) was prepared and employed as a supporting material for aqueous topical gels containing pyridoxine hydrochloride (PYCL) chosen as a hydrophilic model molecule or for O/A emulsion containing beta-carotene chosen as a hydrophobic model molecule. We analyzed the effect of the nature of the crosslinker on the permeation of hydrophilic and lipophilic vitamins through porcine skin by in vitro permeation studies. The vehicles formed by crosslinked poly(methyl vinyl ether-co-maleic anhydride) showed enhanced vitamins permeation with respect to the same vehicles formed by noncrosslinked poly(methyl vinyl ether-co-maleic anhydride) (GZ). The decrease in the crosslinker acyl chain length provides vehicles accelerating the drug permeability through the skin

Poly(Vinylalcohol-Co-Vinyloleate) for the Preparation of Micelles Enhancing Retinyl Palmitate Transcutaneous Permeation

The amphiphilic properties of poly(vinylalcohol) substituted with oleic acid was evaluated to assess the possibility to prepare polymeric micelles in an aqueous phase containing a hydrophobic core able to host lipophilic drugs such as retinyl palmitate and thereby enhance its transcutaneous absorption in the stratum corneum. The effect of the increased drug absorption suggests the possibility of interaction between the substituted polymer and the components present in the intercorneocyte spaces. Correlations between the drug concentration in the preparative mixture, micelle size, and drug permeation were evaluated to establish the best functional properties of the micellar systems enhancing retinyl palmitate absorption. Transcutaneous absorption increased with decreasing micelle size, and micelle size decreased on decreasing the drug concentration in the preparative mixture

Gastroresistant microcapsules: new approaches for site-specific delivery of ketoprofen

Ketoprofen is a potent nonsteroidal anti-inflammatory drug (NSAID) that has been widely used in the treatment of rheumatoid arthritis and other related conditions. However, it carry the risk of undesirable systemic side effects and gastrointestinal irritation at the usual dose of oral administration. The aim of this study was to prepare and evaluate gastroresistant microcapsules containing ketoprofen. Microcapsules were obtained by a spray-drying process starting from a O/A emulsion in presence of different pH-dependent materials (Eudragit® L100, Eudragit® S100 and stearic acid) dissolved in the external phase. The influence of formulation factors (oily phase employed for drug solubilisation, type of coating) on the morphology, particle size distribution, drug loading capacity, in-vitro release and ex-vivo permeation characteristics were investigated. Drug loading capacity was very high for all the microcapsules prepared. Formulation factors did not significatively influence the mean particle size, but modified microcapsule in-vitro and ex-vivo behaviour

Chitosan/pectin polyelectrolyte complexes: Selection of suitable preparative conditions for colon-specific delivery of vancomycin.

The influence of polyelectrolyte complexes composed of chitosan and pectin on the release behaviour of vancomycin has been investigated. Polyelectrolyte complexes between chitosan and pectin were prepared in various pH regions and at different molar ratios by mixing solutions of pectin and chitosan with the same ionic strength. The precipitates were collected by spray-drying and tablets were obtained with the different complexes and vancomycin. FT-IR spectra and TGA thermograms were analysed to study the degree of interactive strength between polyions. In vitro swelling, mucoadhesion and release tests were performed in order to investigate the chitosan/pectin complex ability in the delivery of vancomycin in the gastro-intestinal tract. The results confirmed the formation of polyelectrolyte complexes between pectin and chitosan at pH values in the vicinity of the pK(a) interval of the two polymers. Chitosan/pectin complexes showed a pH-sensitive swelling ability and drug release behaviour suggesting their possible use for colon-specific localization of vancomycin. Among the different complexes, chitosan/pectin complex prepared in molar ratio of 1:9 showed the highest mucoadhesive properties and a pH-dependent swelling sensitivity suitable for colon-delivery. Moreover, the particular composition of these complexes improved vancomycin availability at alkaline pH on the bases of an enzyme-dependent degradation as confirmed from release studies performed in presence of beta-glucosidase

pH-dependent systems for colon delivery of vancomycin

Site-specific controlled release systems offer many advantages over classical methods of drug delivery. These include localized delivery of the drug to a particular part of the body, assurance of drug stability, reduced need for follow up care and optimized drug absorption. In particular the release of orally administred peptidic drugs has attracted growing interest in recent years following the developmet of new delivery systems able to overcome problems due to the acidic environment and enzymatic degradation in the gastrointestinal tract [1]. Chitosan (CH) is a natural derivative of chitin produced by partial N-deacetylation under alkaline conditions. Because of its amino groups, it is a weak base and is insoluble in water and in organic solvents, however it is soluble in dilute aqueous acid solutions (pH < 6.5). Chitosan is a polycation and is able to form salts with a wide variety of acids. Moreover it has interesting biological properties, including biocompatibility and biodegradability and it has been used extensively to prepare hydrogels and microparticles [2]. The aim of this study was to describe a pH-dependent drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan succinate (CH-Suc), chitosan adipate (CH-Ad) and chitosan suberate (CH-Sub) were prepared at different crosslinking degrees by spray-drying and coated with stearic acid by the same technique. Vancomycin hydrochloride was used as a peptidic model drug whose controlled release should minimize its inactivation in the upper part of the gastrointestinal tract. This study characterized the systems in terms of morphology, size, swelling and mucoadhesive properties, drug loading (as assessed by means of an original capillary electrophoresis method) and in particular evaluated, in vitro, the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the uncoated and coated systems at pH 2.0, 5.5 and 7.6. Chitosan salts provided different swelling and release behaviour as a function of diacid chain length and crosslinking degree according to a different polymer ability to interact with water. Moreover chitosan salts showed different swelling and release behaviour as a function of enviromental pH according to the net charge balance inside the gel. The coating process was found to prevent vancomicyn release in acidic conditions allowing the complete release of the peptidic drug in the intestinal fluids. Chitosan salts coated with stearic acid could serve as potential candidates for antibiotic colon-specific delivery. References [1] G. Van den Mooter , Expert Opin. Drug Deliv. 3 (2006) 111. [2] T. Cerchiara, B. Luppi, F. Bigucci and V. Zecchi, J. Pharm. Pharmacol. 55 (2003) 1623

Spartium junceum Aromatic Water: chemical composition and antitumor activity

none8noThe purpose of this study was to analyse the chemical composition of Spartium junceum L. (also known as Spanish Broom) aromatic water and to evaluate its cytotoxic activity against a series of human cancer cell lines (melanoma: RPMI 7932; leukaemia: K562; breast cancer cell: MCF7-Bart and MCF7-ICLC, colon adenocarcinoma: SW480). The results show that aromatic water was cytotoxic toward the tumor cell lines analysed (RPMI 7932, K562, MCF7-Bart, MCF7-ICLC, SW480), while it did not appreciably alter the viability of the normal keratinocyte (NCTC 2544) suggesting its potential use as an antitumoral agent for cancer treatment and/or prevention.noneT. Cerchiara; S.V. Straface; G. Chidichimo; E.L. Belsito; A. Liguori; B. Luppi; F. Bigucci; V. ZecchiT. Cerchiara; S.V. Straface; G. Chidichimo; E.L. Belsito; A. Liguori; B. Luppi; F. Bigucci; V. Zecch

Multifunctional liposomes encapsulating anti-Alzheimer drug for nasal delivery to central nervous system

The purpose of this work was the formulation of liposomes for nasal administration of tacrine-HCl. This route has many advantages; in particular is possible to convey the drug directly to the Central Nervous System, through the olfactory bulb. Part of Tacrine administered can also be absorbed into the systemic circulation avoiding hepatic first pass effect. Liposomes were formulated with ingredients that have a beneficial effect against the disease. In particular, the classical excipients cholesterol and phosphatidylcholine were enriched with α-tocopherol and polyunsaturated fatty acid EPA and DHA. This formulative approach allowed us to obtain 100% active liposomes against symptoms of Alzheimer's disease