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Stabilization of 10-Hydroxycamptothecin in Poly(lactide-co-glycolide) Microsphere Delivery Vehicles

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Abstract

Purpose. 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°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.

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Authors and Affiliations

  1. Division of Pharmaceutics and Pharmaceutical Chemistry, College of Pharmacy, The Ohio State University, 500 West 12th Ave., Columbus, Ohio, 43210

    Anna Shenderova, Thomas G. Burke & Steven P. Schwendeman

  2. Department of Medicinal Chemistry and Pharmaceutics, College of Pharmacy, and The Markey Cancer Center, University of Kentucky, Lexington, Kentucky, 40506

    Thomas G. Burke

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  1. Anna Shenderova
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  2. Thomas G. Burke
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  3. Steven P. Schwendeman
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Correspondence to Steven P. Schwendeman.

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Shenderova, A., Burke, T.G. & Schwendeman, S.P. Stabilization of 10-Hydroxycamptothecin in Poly(lactide-co-glycolide) Microsphere Delivery Vehicles. Pharm Res 14, 1406–1414 (1997). https://doi.org/10.1023/A:1012172722246

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