Poly(ω-pentadecalactone-co-butylene-co-succinate) nanoparticles as biodegradable carriers for camptothecin delivery

Abstract

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(ω-pentadecalactone- co-butylene-co-succinate) (PPBS) copolyesters. PPBS copolymers with various compositions (20–80 mol% PDL unit contents) were synthesized via copolymerization of ω-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 −10 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 CPT-loaded PPBS nanoparticles incubated in both phosphate-buffered saline (PBS, pH = 7.4) and DMEM medium for at least 24 hr. In PBS at 37 °C, CPT-loaded PPBS nanoparticles showed a low burst CPT release (20–30%) within the first 24 hrs 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.

Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells

“…Delivery of acetylthevetin B, an antitumor cardiac glycoside, using polymeric micelles for enhanced therapeutic efficacy against lung cancer cells targeting phenomenon, commonly referred to as an enhanced permeability and retention (EPR) effect [7,8] . Inspired by the superiority of nanosized micelles, we intended to deliver CGs to tumor cells using polymeric micelles, which may enhance antitumor efficacy and decrease the cardiotoxicity associated with these drugs.…”

Candida antarctica Lipase B as Catalyst for Cyclic Esters Synthesis, Their Polymerization and Degradation of Aliphatic Polyesters

“…Moreover, they are playing an important role as effective and safe drug delivery platforms [119] for e.g. camptothecin [120], daunorubicin [121] and ibuprofen [122]. In the presented article, it was also demonstrated that CALB is an efficient catalyst in (bio)degradation process, which provides to reduce environmental pollution.…”

Synthetic high-density lipoproteins for delivery of 10-hydroxycamptothecin

“…The HPLC method to detect HCPT concentration and lactoneto-carboxylate ratio was adapted from Liu et al 23 The HPLC instrument consisted of a Waters 2695 system equipped with an Ascentis C18 separation column (15 cm ×4.6 mm, 5 µm). The mobile phase consisted of 50 mM phosphate buffer (pH 6.0), acetonitrile, and tetrahydrofuran (80:18:2, v/v).…”