In-situ forming gel-like depot of a polyaspartamide-polylactide copolymer for once a week administration of Sulpiride

Abstract Objectives An in-situ forming gel-like depot, prepared by using an appropriate polyaspartamide-polylactide graft copolymer, has been employed to release in a sustained way sulpiride. Methods α,β-poly(N-2-hydroxyethyl)-D,L-aspartamide-g-polylactic acid (PHEA-g-PLA) has been used as a polymer component. Its physicochemical properties make possible to dissolve it in N-methyl-2-pyrrolidone, with the obtainment of a solution able to form a gel-like depot once injected into a physiological medium. Cell compatibility of PHEA-g-PLA depot has been investigated, using murine dermal fibroblasts as cell model. 3-(4,5-Dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazo…

A new hyaluronic acid pH sensitive derivative obtained by ATRP for potential oral administration of proteins

Atom transfer radical polymerization (ATRP) has been successfully employed to obtain a new derivative of hyaluronic acid (HA) able to change its solubility as a function of external pH and then to be potentially useful for intestinal release of bioactive molecules, included enzymes and proteins. In particular, a macroinitiator has been prepared by linking 2-bromo-2-methypropionic acid (BMP) to the amino groups of ethylenediamino derivative of tetrabutyl ammonium salt of HA (HA-TBA-EDA). This macroinititor, named HA-TBA-EDA-BMP has been used for the ATRP of sodium methacrylate (MANa) using a complex of Cu(I) and 2,2'-bipyridyl (Byp) as a catalyst. The resulting copolymer, named HA-EDA-BMP-MA…

TABLET DI ACIDO IALURONICO FUNZIONALIZZATO CON CATENE IDROFOBICHE PER IL RILASCIO LOCOREGIONALE DI PACLITAXEL

INULIN BASED HYDROGEL FOR ORAL DELIVERY OF FLUTAMIDE: PREPARATION, CHARACTERIZATION AND IN VIVO RELEASE STUDIES

The ability of a hydrogel obtained by crosslinking INUDV and PEGBa to facilitate sustained release of flutamide is examined. The hydrogel is prepared in pH = 7.4 PBS and no toxic solvents or catalysts are used. It is recovered in microparticulate form and its size distribution is determined. Mucoadhesive properties are evaluated in vitro by reproducing gastrointestinal conditions. Flutamide is loaded into the hydrogel using a post-fabrication encapsulation procedure that allows a drug loading comparable to that of market tablets. Drug-loaded microparticles are orally administered to cross-bred dogs and the in vivo study demonstrates their ability to prolong the half-life of the principal ac…

Biomaterials for Biotechnological and Pharmaceutical application

HYALURONIC ACID-graft-ELASTIN BASED SCAFFOLDS FOR POTENTIAL TISSUE ENGINEERING APPLICATIONS

Injectable in situ forming microgels of hyaluronic acid-g-polylactic acid for methylprednisolone release

Abstract A hydrophobic derivative of hyaluronic acid (HA), obtained by grafting polylactic acid (PLA) to the polysaccharide, has been exploited to produce injectable in situ forming microgels. First of all, self assembling properties of HA-g-PLA copolymer have been evaluated by determining the critical aggregation concentration (CAC) value, then this copolymer has been dissolved in a mixture water/NMP 5:2 v/v with a concentration greater than CAC. When solutions at 1% or 2% w/v were injected into Dulbecco phosphate buffer solution (DPBS) pH 7.4, microgels promptly are formed. Their stability in DPBS pH 7.4 in the absence or in the presence of hyaluronidase and cell compatibility have been e…

DERIVATI IBRIDI DELL’ACIDO IALURONICO PER APPLICAZIONI BIOMEDICHE E FARMACEUTICHE

Self-assembling and auto-crosslinkable hyaluronic acid hydrogels with a fibrillar structure

Abstract A hyaluronic acid derivative bearing pendant l -benzoyl-cysteine portions (with a derivatization degree equal to 10 mol.%) was synthesized by linking N,N′-dibenzoyl- l -cystine to the polysaccharide and then reducing its disulfide bridge to thiol groups. The formation of π–π stacking interactions between the benzoyl moieties was studied by fluorescence spectroscopy as a function of polymer concentration and oxidation time. The efficiency of oxidation of thiol groups to disulfide bridges occurring in phosphate buffer pH 7.4, was determined by colorimetric assays. The hydrogel formed by means of oxidative crosslinking has shown the presence of fibrillar aggregates as detected by ligh…

PRODUCTION OF MICELLES FROM HYALURONIC ACID AMPHIPHILIC DERIVATIVES FOR TARGETED RELEASE OF DOXORUBICIN

Medicated hydrogels of hyaluronic acid derivatives for use in orthopedic field

Medicated hydrogels of hyaluronic acid derivatives for use in orthopedic field.

Physical hydrogels have been obtained from hyaluronic acid derivatized with polylactic acid in the presence or in the absence of polyethylene glycol chains. They have been extemporarily loaded with antibacterial agents, such as vancomycin and tobramycin. These medicated hydrogels have been used to coat titanium disks (chosen as simple model of orthopedic prosthesis) and in vitro studies in simulated physiological fluid have been performed as a function of time and for different drug loading and polymer concentration values. Sterilization process performed on the hydrogels does not change their rheological behavior and release properties as well as the chemical structure of starting copolyme…

Electrospinning of α,β-poly(N-2-hydroxyethyl)-dl-aspartamide-graft-polylactic acid to produce a fibrillar scaffold

Abstract α,β-Poly( N -2-hydroxyethyl)- dl -aspartamide grafted with polylactic acid (PHEA- g -PLA) is a biocompatible and biodegradable amphiphilic copolymer that has been already employed to prepare a drug delivery system. In this study we have prepared for the first time a fibrillar scaffold from PHEA- g -PLA by the electrospinning of a solution of this copolymer in a mixture of N , N -dimethyl formamide (DMF) and acetone (80:20 vol/vol). The average diameter and the morphology of electrospun fibers were detected by scanning electron microscopy. Chemical degradation studies in phosphate buffer solution pH 7.4 have been performed until 15 days in order to obtain a preliminary information a…

ANTICANCER RELEASING FILMS AND POROUS SCAFFOLDS BASED ON PHYSICALLY ASSEMBLED HYALURONIC ACID DERIVATIVES

POROUS SCAFFOLDS BASED ON PLLA/FUNCTIONALISED POLYMERS BLENDS PRODUCED BY THERMALLY INDUCED PHASE SEPARATION

Inulin-Based Hydrogel for Oral Delivery of Flutamide: Preparation, Characterization, and in vivo Release Studies

The ability of a hydrogel obtained by crosslinking INUDV and PEGBa to facilitate sustained release of flutamide is examined. The hydrogel is prepared in pH 7.4 PBS and no toxic solvents or catalysts are used. It is recovered in microparticulate form and its size distribution is determined. Mucoadhesive properties are evaluated in vitro by reproducing gastrointestinal conditions. Flutamide is loaded into the hydrogel using a post-fabrication encapsulation procedure that allows a drug loading comparable to that of market tablets. Drug-loaded microparticles are orally administered to cross-bred dogs and the in vivo study demonstrates their ability to prolong the half-life of the principal acti…

Polyaspartamide-polylactide electrospun scaffolds for potential topical release of Ibuprofen.

In this work, the production and characterization of electrospun scaffolds of the copolymer α,β-poly(N-2-hydroxyethyl)-DL-aspartamide-graft-polylactic acid (PHEA-g-PLA), proposed for a potential topical release of Ibuprofen (IBU), are reported. The drug has been chemically linked to PHEA-g-PLA and/or physically mixed to the copolymer before electrospinning. Degradation studies have been performed as a function of time in Dulbecco phosphate buffer solution pH 7.4, for both unloaded and drug-loaded scaffolds. By using an appropriate ratio between drug physically blended to the copolymer and drug-copolymer conjugate, a useful control of its release can be obtained. MTS assay on human dermal fi…

Polyaspartamide-polylactide electrospun scaffolds for potential topical release of ibuprofen

MICELLES OF AMPHYPHLIC HYALURONIC ACID DERIVATIVES FOR TARGETED DELIVERY OF DOXORUBICIN

BIODEGRADABLE POLYASPARTAMIDE-GRAFT-POLYESTER COPOLYMER FOR VASCULAR REGENERATION

HYDROGELS OF HYALURONIC ACID-GRAFT-alfa-ELASTIN AS EXTRACELLULAR MATRIX SUBSTITUTES

SELF ASSEMBLED AND CROSSLINKED FIBRILLAR SCAFFOLDS FOR CARTILAGE REGENERATION.

In situ gel forming graft copolymers of a polyaspartamide and polylactic acid: Preparation and characterization

Abstract In situ gel forming systems have been prepared by linking polylactic acid (PLA) to a water soluble and polyfunctional polymer, such as α,β-poly( N -2-hydroxyethyl)- d , l -aspartamide (PHEA). Three graft copolymers PHEA–PLA with a different derivatization degree in PLA, have been synthesized and characterized. PHEA–PLA graft copolymer with the highest amount in PLA has been used to prepare solutions in organic solvents able to give rise to gel-like matrices when injected into phosphate buffered saline solution. The chemical degradation of these gels has been evaluated and in vitro tests have been performed to evaluate the cell compatibility of the hydrolysis products. The possibili…