Designing bioresorbable polyester matrices for controlled doxorubicin release in glioma therapy.
The influence of the chain microstructure on release process of doxorubicin from polymeric matrices was analyzed. Aliphatic polyester copolymers with optimal chain microstructure, i.e. poly(glycolide-co-L-lactide, 15/85) (PGLA) and poly(glycolide-co-epsilon-caprolactone, 10/90) (PGCA) were synthesized for long-term doxorubicin delivery systems. Various release profiles from PGLA and PGCA matrices were obtained. The investigations revealed the most steadily doxorubicin release from PGCA matrices with 5% (w/w) of drug content. Degradation of matrices with and without drug was monitored by means of NMR spectroscopy and confirmed stability of degradation process. From PGCA matrices the increase of released doxorubicin amount was observed during first 60 days. On the contrary in case of matrices obtained from PGLA the delay of doxorubicin release was observed during first 50 days, what was caused by interaction of drug molecules with polylactide chain of polymer matrix. The interaction between doxorubicin molecules and polylactide chains was confirmed by IR spectroscopy. This fact can be used for designing of delivery systems consisting of combination of matrices with different microstructure of copolymer chains in order to adjust concentration of released doxorubicin and stabilization of drug release process.
Kasperczyk
J
J
Department of Biopharmacy, School of Pharmacy, Medical University of Silesia, Narcyzów 1 St., 41-200 Sosnowiec, Poland. janusz.kasperczyk@cmpw-pan.edu.pl
Stoklosa
K
K
Dobrzynski
P
P
Stepien
K
K
Kaczmarczyk
B
B
Dzierzega-Lecznar
A
A
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry* / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy*; D002555:Cerebrospinal Fluid / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004317:Doxorubicin / Q000737:chemistry* / Q000627:therapeutic use; D004337:Drug Carriers; D004339:Drug Compounding; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D006868:Hydrolysis; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D011091:Polyesters; C516442:poly(glycolide-co-caprolactone); D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004317:Doxorubicin