Poly(ω-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery
✍ Scribed by Jie Liu; Zhaozhong Jiang; Shengmin Zhang; W. Mark Saltzman
- Publisher
- Elsevier Science
- Year
- 2009
- Tongue
- English
- Weight
- 768 KB
- Volume
- 30
- Category
- Article
- ISSN
- 0142-9612
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✦ Synopsis
In this study, we show that degradable particles of a hydrophobic polymer can effectively deliver drugs to tumors after i.v. administration. Free-standing nanoparticles with diameters of 100-300 nm were successfully fabricated from highly hydrophobic, biodegradable poly(u-pentadecalactone-co-butyleneco-succinate) (PPBS) copolyesters. PPBS copolymers with various compositions (20-80 mol% PDL unit contents) were synthesized via copolymerization of u-pentadecalactone (PDL), diethyl succinate (DES), and 1,4-butanediol (BD) using Candida antarctica lipase B (CALB) as the catalyst. Camptothecin (CPT, 12-22%) was loaded into PPBS nanoparticles with high encapsulation efficiency (up to 96%) using a modified oil-in-water single emulsion technique. The CPT-loaded nanoparticles had a zeta potential of about À10 mV. PPBS particles were non-toxic in cell culture. Upon encapsulation, the active lactone form of CPT was remarkably stabilized and no lactone-to-carboxylate structural conversion was observed for CPTloaded PPBS nanoparticles incubated in both phosphate-buffered saline (PBS, pH ¼ 7.4) and DMEM medium for at least 24 h. In PBS at 37 C, CPT-loaded PPBS nanoparticles showed a low burst CPT release (20-30%) within the first 24 h followed by a sustained, essentially complete, release of the remaining drug over the subsequent 40 days. Compared to free CPT, CPT-loaded PPBS nanoparticles showed a significant enhancement of cellular uptake, higher cytotoxicity against Lewis lung carcinoma and 9L cell lines in vitro, a longer circulation time, and substantially better antitumor efficacy in vivo. These results demonstrate the potential of PPBS nanoparticles as long-term stable and effective drug delivery systems in cancer therapy.