Injectable nanospheres from a novel multiblock copolymer: cytocompatibility, degradation and in vitro release studies

Abstract

The aim was to develop and characterize nanospheres made from a newly synthesized poly (D,L-lactide-co-ethyleneglycol) (-PLA-PEG-PLA-)n multiblock copolymer. Nanospheres were prepared under optimized conditions of modified emulsion-solvent evaporation technique in a continuous flow process using rhodamine B as a drug model. They were characterized for size distribution, zeta (zeta) potential, porosity and morphology. Drug loading and yield were also determined. In vitro degradation studies of the copolymer were conducted in phosphate buffer (pH 7.4) at 37 degrees C. The cytotoxic properties of the polymer and vector were analysed by dimethylthiazoldiphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays on the B16 mouse cell line. Release of rhodamine B from the nanospheres was assayed in vitro using a dialysis bag in isotonic phosphate buffer (pH 7.4) at 37 degrees C. Spherical and non-porous nanospheres with mean size less than 800 nm could be prepared. The (zeta) potential was neutral. The average yield was approximately 70% with 7% rhodamine loading. A total of 50% of the multiblock underwent initial degradation after 4 weeks, while degradation was complete after 16 weeks. Cellular proliferation was not inhibited as no cytotoxicity was observed with the copolymers and nanospheres. Rhodamine B was released in a stepwise pattern. The initial burst was 20%, and release was prolonged thereafter for 29 days. Thus, injectable nanospheres with prolonged rhodamine B release have been designed and characterized as a potential drug-delivery system.

Phase behavior and structure formation in linear multiblock copolymer solutions by Monte Carlo simulation

“…Current experimental research efforts aim to exploit the solution phase self-assembly of low molecular weight multiblock copolymers in novel applications, particularly in the field of protein-based drug delivery. [46][47][48][49][50][51][52][53][54] Amphiphilic multiblock copolymers are thought to offer more flexibility in tailoring properties of a delivery system than comparable di-and triblock copolymers. The use of multiple short amphiphilic segments in one polymer has been shown to prevent the rapid and preferential loss of one polymer type, allowing for modulated drug release profiles and leading to an overall enhanced stability of the microstructure.…”

γ-Irradiation of PEGd,lPLA and PEG-PLGA Multiblock Copolymers: I. Effect of Irradiation Doses

“…Moreover, the PEG segments confer stealth behaviour to the micro-or nanoparticulate drug delivery systems. Stealth particles have the ability to evade the immune system and circulate after injection for longer periods of time without any clearance from immune system, increasing their effective lifespan (15)(16). Aim of this work was to submit the polymers to irradiation doses up to 50 kGy, to evaluate the effect of irradiation treatment on multiblock copolymers (PEGd,lPLA and PEG-PLGA) and to compare the behaviour of the multiblock copolymers to that of PLA and PLGA polymers, respectively.…”

Synthesis of PLA-b-PEG Multiblock Copolymers for Stealth Drug Carrier Preparation

“…They are solid enough to prepare microspheres and the presence of PEG ensures the stealth behavior. Others studies from Panoyan et al already show in vitro and in vivo behavior for some of theses polymers [ 15 ].…”