pH-Sensitive Micelles for Targeted Drug Delivery Prepared Using a Novel Membrane Contactor Method

Abstract

A novel membrane contactor method was used to produce size-controlled poly(ethylene glycol)-b-polycaprolactone (PEG-PCL) copolymer micelles composed of diblock copolymers with different average molecular weights, M n (9200 or 10 400 Da) and hydrophilic fractions, f (0.67 or 0.59). By injecting 570 L m −2 h −1 of the organic phase (a 1 mg mL −1 solution of PEG-PCL in tetrahydrofuran) through a microengineered nickel membrane with a hexagonal pore array and 200 μm pore spacing into deionized water agitated at 700 rpm, the micelle size linearly increased from 92 nm for a 5-μm pore size to 165 nm for a 40-μm pore size. The micelle size was finely tuned by the agitation rate, transmembrane flux and aqueous to organic phase ratio. An encapsulation efficiency of 89% and a drug loading of ∼75% (w/w) were achieved when a hydrophobic drug (vitamin E) was entrapped within the micelles, as determined by ultracentrifugation method. The drug-loaded micelles had a mean size of 146 ± 7 nm, a polydispersity index of 0.09 ± 0.01, and a ζ potential of −19.5 ± 0.2 mV. When drug-loaded micelles where stored for 50 h, a pH sensitive drug release was achieved and a maximum amount of vitamin E (23%) was released at the pH of 1.9. When a pH-sensitive hydrazone bond was incorporated between PEG and PCL blocks, no significant change in micelle size was observed at the same micellization conditions.

Preparation of biodegradable polymeric nanoparticles for pharmaceutical applications using glass capillary microfluidics

“…Therefore, a larger number of nuclei will lead to smaller size of NPs. The smaller particle sizes at higher aqueous-to-organic volume ratios were also obtained by Laouini et al (2013aLaouini et al ( , 2013bLaouini et al ( , 2013c in the production of liposomes and polymeric micelles in membrane contactors and by Jahn et al (2010) in the formation of liposomes in planar flow focusing microfluidic mixers.…”

“…Membrane micromixing is an alternative strategy of controlled mixing at molecular scale that was combined with nanoprecipitation to produce inorganic nanoparticles (Jia and Liu, 2013), liposomes (Laouini et al, 2013a), micelles (Laouini et al (2013c), and PCL nanoparticles (Khayata et al, 2012). In a membrane-dispersion reactor, one liquid phase is dispersed through a microporous membrane into another liquid under controlled shear conditions and injection rate.…”

Preparation of chitosan–TPP nanoparticles using microengineered membranes – Effect of parameters and encapsulation of tacrine

“…The increasing interest for this technique is due to control of flow, mixing and/or reaction between two phases, and to the fact that the method is easy to scale-up by increasing the membrane surface. The technique has been applied to the preparation of a very large range of colloids including emulsions [20], lipid and polymeric nanoparticles [21,22], albumin nanoparticles [23], nanoemulsions [24], liposomes [25] and micelles [26]. Several membranes have been tested, such as nickel microengineered membranes (Micropores Technologies, UK).…”

Production of liposomes using microengineered membrane and co-flow microfluidic device

“…Microengineered membranes have been recently used for production of liposomes and micelles [20,21]. In this work, for the first time the experimental data obtained in membrane and microfluidic devices are compared for the same product formulation.…”