Branched biodegradable polyesters for parenteral drug delivery systems.
Continuous, 'infusion-like' drug release profiles from biodegradable parenteral delivery systems are difficult to achieve for proteins and other hydrophilic macromolecular drugs with commonly used linear polyesters from lactic acid (PLA) and its random copolymers with glycolic acid (PLG). Drug release rates can be modified either by increasing the hydrophilicity of polyesters or by manipulating the polymer architecture to adjust polymer degradation rates and thus drug release. Therefore, we investigated different branching concepts for biodegradable polyesters of PLA and PLG. For one four- and eight-arm poly(ethylene oxide)s (PEO) were grafted with shorter polyester chains leading to star-branched structures. Secondly we obtained comb-like polyesters using both charged and uncharged dextrans or poly(vinyl alcohol)s (PVA) as hydrophilic backbones. The star-shaped and brush-like grafted polymers were intensively characterized by methods, such as NMR, IR, SEC-SLS, DSC and viscosity measurements. Tailor-made properties make these novel biodegradable polyesters promising candidates for parenteral protein delivery systems. While the star-branched polyesters have shown some interesting properties with respect to their degradation behavior, retaining the PEO blocks longer than ABA triblock copolymers, their release properties need further optimization. Brush-like branched polyesters on the other hand seem to possess both degradation and release properties meriting further investigations for parenteral protein delivery systems.
Breitenbach
A
A
Department of Pharmaceutics and Biopharmacy, Philipps University, Ketzerbach 63, D-35037, Marburg, Germany.
Li
Y X
YX
Kissel
T
T
D001673:Biodegradation, Environmental; D003911:Dextrans / Q000737:chemistry / Q000493:pharmacokinetics*; D016503:Drug Delivery Systems / Q000379:methods*; D016650:Fluorescein-5-isothiocyanate; D006016:Glycolates / Q000737:chemistry; D007263:Infusions, Parenteral; D019344:Lactic Acid / Q000737:chemistry; D008863:Microspheres; D011091:Polyesters / Q000737:chemistry* / Q000493:pharmacokinetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011142:Polyvinyl Alcohol; D012995:Solubility; D013997:Time Factors
D003911:Dextrans; D006016:Glycolates; D011091:Polyesters; D011108:Polymers; C031149:glycolic acid; D019344:Lactic Acid; D011092:Polyethylene Glycols; C033616:poly(lactide); D011142:Polyvinyl Alcohol; D016650:Fluorescein-5-isothiocyanate