Hydrolytic degradation and drug release of ricinoleic acid-lactic acid copolyesters.

A systematic study on the degradation and drug release from L-lactic acid and ricinoleic-acid-based copolyesters is reported. These copolyesters were synthesized by ring opening polymerization (ROP), melt condensation (COND) and transesterification (TRANS) of high molecular weight poly(lactic acid) (PLA) with ricinoleic acid (PLA-RA), and repolymerization by condensation to yield random and block copolymers of weight average molecular weights (Mw) between 3000 and 13,000. All polymers showed an almost zero-order weight loss, with a 20-40% loss after 60 days of incubation. Lactic acid release to the degradation solution is proportional to weight loss of the polymer samples. The main decrease in molecular weight was observed during the first 20 days, followed by a slow degradation phase, which kept the number average molecular weight (Mn) at 4000-2000 for another 40 days. Water-soluble 5FU was released from ricinoleic-acid-based polymers faster than slightly water-soluble triamcinolone. Drug release into phosphate-buffered saline (pH 7.4, 0.1 M) at 37 degrees C from P(LA-RA) 60:40 prepared by condensation of the acids was faster than from pasty P(PLA-RA) 60:40 synthesized by transesterification for both drugs.

Macrolactones and polyesters from ricinoleic acid.

A systematic study on the synthesis, characterization, and polymerization of ricinoleic acid (RA) lactone is reported. Ricinoleic acid lactones were synthesized by refluxing pure ricinoleic acid in chloroform (10 mg/mL) with dicyclohexylcarbodimide and (dimethylamino)pyridine as catalyst. Purification of RA lactones was performed by silica gel chromatography. The reaction resulted in a 75% yield of ricinoleic acid lactones. IR and NMR analysis confirmed the formation of cyclic compounds. Polymerization of the ricinoleic acid lactones with catalysts commonly used for ring-opening polymerization of lactones, under specific reaction conditions, resulted in oligomers. Copolymerization with lactide (LA) by ring-opening polymerization, using Sn(Oct) as catalyst, yielded copolyesters with molecular weights (M(w)) in the range of 5000-16000 and melting temperatures of 100-130 degrees C for copolymers containing 10-50% w/w ricinoleic acid residues. Degradation studies of the copolymers were performed in 0.1 M phosphate buffer solution, pH 7.4, at 37 degrees C. P(LA-RA)s with up to 20% w/w RA slowly degraded and released only approximately 7% of its lactic acid content after 60 days of study, while pure PLA under similar conditions released more than 20% of its lactic acid content. On the other hand, copolyesters containing more then 20% w/w RA degraded and released lactic acid faster than pure PLA due to the low crystallinity of the copolymers.

Stereocomplexes of enantiomeric lactic acid and sebacic acid ester-anhydride triblock copolymers.

A systematic study on the synthesis, characterization, degradation, and drug release of d-, l-, and dl-poly(lactic acid) (PLA)-terminated poly(sebacic acid) (PSA) and their stereocomplexes is reported. PLA-terminated sebacic acid polymers were synthesized by melt condensation of the acetate anhydride derivatives of PLA oligomers and sebacic anhydride oligomers to yield ABA triblock copolymers of molecular weights between 3000 and 9000 that melt at temperatures between 35 and 80 degrees C. Pairs of the corresponding enantiomeric ABA copolymers composed of l-PLA-PSA-l-PLA and d-PLA-PSA-d-PLA were solvent mixed to form stereocomplexes. The formed stereocomplexes exhibited higher crystalline melting temperature than the enantiomeric polymers, which indicate stereocomplex formulation. The PLA terminals had a significant effect on the polymer degradation and drug release rate. PSA with up to 20% w/w of PLA terminals degraded and released the incorporated drug for more than 3 weeks as compared with 10 days for PSA homopolymer.