title: PLGAs bearing carboxylated side chains: novel matrix formers with improved properties for controlled drug delivery.
abstract: Novel PLGA derivatives bearing carboxylated side chains have been synthesized and used to encapsulate the fragile drug apomorphine HCl with a solid-in-oil-in-water solvent extraction/evaporation method. Blends of d,l-lactide and l-3-(2-Benzyloxycarbonyl)Ethyl-1,4-Dioxane-2,5-dione (BED) were co-polymerized at different ratios via ring-opening using benzyl alcohol as initiator. Optionally, the ester groups in the side chains as well as the terminal ester groups were hydrogenolyzed (leading to free COOH groups). For reasons of comparison, different types of "conventional" PLGAs were also synthesized and used for apomorphine HCl encapsulation. The polymers and microparticles were thoroughly characterized using SEC, (1)H NMR, DSC, SEM, X-ray and laser diffraction, Headspace-GC as well as in vitro drug release measurements in flow-through cells and agitated flasks. Importantly, microparticles based on the new polymers bearing carboxylic groups in the polymeric side chains: (i) allowed a significant reduction of the amount of residual solvent (dichloromethane), and (ii) provided different types of drug release patterns compared to microparticles based on "conventional" PLGAs (at least partially due to altered polymer degradation kinetics). Thus, they offer an interesting potential as novel matrix formers in controlled drug delivery systems, overcoming potential shortcomings of standard PLGAs.
authors.affiliation: University of Lille, College of Pharmacy, 3 Rue du Prof. Laguesse, 59006 Lille, France; INSERM U 1008, Controlled Drug Delivery Systems and Biomaterials, 3 Rue du Prof. Laguesse, 59006 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Regnier-Delplace
authors.forename: O
authors.initials: O
authors.lastname: Thillaye du Boullay
authors.forename: F
authors.initials: F
authors.lastname: Siepmann
authors.forename: B
authors.initials: B
authors.lastname: Martin-Vaca
authors.forename: P
authors.initials: P
authors.lastname: Demonchaux
authors.forename: O
authors.initials: O
authors.lastname: Jentzer
authors.forename: F
authors.initials: F
authors.lastname: Danède
authors.forename: M
authors.initials: M
authors.lastname: Descamps
authors.forename: J
authors.initials: J
authors.lastname: Siepmann
authors.forename: D
authors.initials: D
authors.lastname: Bourissou
mesh_terms: D001058:Apomorphine / Q000008:administration & dosage*; D002152:Calorimetry, Differential Scanning; D002264:Carboxylic Acids / Q000737:chemistry*; D002850:Chromatography, Gel; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D019344:Lactic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning; D015394:Molecular Structure; D010316:Particle Size; D011100:Polyglycolic Acid / Q000138:chemical synthesis / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D052616:Solid Phase Extraction; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013499:Surface Properties; D014961:X-Ray Diffraction
chemical_list: D002264:Carboxylic Acids; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D001058:Apomorphine