Preparation of self-solidifying polymeric depots from PLEC-PEG-PLEC triblock copolymers as an injectable drug delivery system

Abstract

Copolymers of (D,L-lactide-random-ε-caprolactone)-block-poy(ethylene glycol)-block-(D,L-lactide-random-ε-caprolactone) or PLEC were explored as materials for injectable drug delivery system. A series of six PLECs were successfully synthesized with varied D,L-lactide (LA) content (0, 10 and 20%) and molecular weight (20 and 50 kDa). All polymers were able to form depots with more than 90% encapsulation efficiency of trypan blue leading to the loading density as high as 27% w/w. The variation of trypan blue loading, LA content and molecular weight were found to have profound effects on trypan blue release profiles. Even though, GPC and SEM confirmed the higher degradation of PLEC chains, trypan blue release rate and burst release was greater as the content of hydrophilic moiety, i.e. LA, was decreased. This was primarily due to the smooth and dense surface and cross-section of PLEC depots. The results from this study suggest a possible application of these depots as injectable, self-solidifying drug delivery systems.

Antitumor efficacy and intratumoral distribution of SN-38 from polymeric depots in brain tumor model

“…22 SN-38 was purchased from Abatra Technology Company Ltd (Xi'an, Shaanxi, China). Glycofurol was obtained from Sigma-Aldrich (St. Louis, Missouri).…”

HPLC analysis and extraction method of SN-38 in brain tumor model after injected by polymeric drug delivery system

“…PLECs were polymerized and sterilized as described in the previous reports. 15 30, v/v %). In all instances, an injection volume was 10 mL and a flow-rate of 1.0 mL/min was employed.…”

“…PLECs were polymerized and sterilized as described in the previous reports. 15,18,19 Dimethyl sulphoxide (DMSO), phosphoric acid, chloroform, hexane, tetrahydrofuran (THF), acetonitrile, and methanol (HPLC grades) were purchased from RCI Labscan Ltd. (Milwaukee, WI, USA). Sodium phosphate monobasic (NaH 2 PO 4 H 2 O) was obtained from Mallinckrodt Baker, Inc. (St. Louis, MO, USA).…”

“…PLECs were polymerized and sterilized as described in the previous reports. 15,18,19 O which was adjusted to pH 3.1 using phosphoric acid and acetonitrile solution (70:30, v/v %). In all instances, an injection volume was 10 mL and a flow-rate of 1.0 mL/min was employed.…”

“…One strategy is to use biodegradable polymers for SN-38 delivery such as nanoparticles, 8 micelles, [9][10][11] liposomes, 12 or dendrimer. 4 Not only systemic drug delivery systems, but many local drug delivery systems also have been developed such as polymer millirods, 13 wafers, 14 or self-forming polymeric depots 15 for continuously controlled release of SN-38. Tremendous advantages of local implant drug delivery systems have been reported such as improvement of therapeutic efficiency, reduction of anticancer drug toxicity, and minimally invasive methods.…”