Stabilization of 10-hydroxycamptothecin in poly(lactide-co-glycolide) microsphere delivery vehicles.
OBJECTIVE
The purpose of this study was to investigate the potential of poly(lactide-co-glycolide) (PLGA) microspheres to stabilize and deliver the analogue of camptothecin, 10-hydroxycamptothecin (10-HCPT).


METHODS
10-HCPT was encapsulated in PLGA 50:50 microspheres by using an oil-in-water emulsion-solvent evaporation method. The influence of encapsulation conditions (i.e., polymer molecular weight (Mw), polymer concentration, and carrier solvent composition) on the release of 10-HCPT from microspheres at 37 degrees C under perfect sink conditions was examined. Analysis of the drug stability in the microspheres was performed by two methods: i) by extraction of 10-HCPT from microspheres and ii) by sampling release media before lactone--carboxylate conversion could take place.


RESULTS
Microspheres made of low Mw polymer (inherent viscosity 0.15 dl/g) exhibited more continuous drug release than those prepared from polymers of higher Mw (i.v. = 0.58 and 1.07 dl/g). In addition, a high polymer concentration and the presence of cosolvent in the carrier solution to dissolve 10-HCPT were both necessary in the microsphere preparation in order to eliminate a large initial burst of the released 10-HCPT. An optimal microsphere formulation released 10-HCPT slowly and continuously for over two months with a relatively small initial burst of the released drug. Both analytical methods used to assess the stability of 10-HCPT revealed that the unreleased camptothecin analogue in the microspheres remained in its active lactone form (> 95%) over the entire 2-month duration of study.


CONCLUSIONS
PLGA carriers such as those described here may be clinically useful to stabilize and deliver camptothecins for the treatment of cancer.
Shenderova
A
A
Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, Ohio State University, Columbus 43210, USA.
Burke
T G
TG
Schwendeman
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SP
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D003692:Delayed-Action Preparations; D004355:Drug Stability; D019344:Lactic Acid / Q000737:chemistry; D018613:Microscopy, Confocal; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D008970:Molecular Weight; D014677:Pharmaceutical Vehicles; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry
D000972:Antineoplastic Agents, Phytogenic; D003692:Delayed-Action Preparations; D014677:Pharmaceutical Vehicles; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C028098:10-hydroxycamptothecin; D002166:Camptothecin