Novel pH Sensitive Block Copolymer Micelles for Solvent Free Drug Loading

Abstract

Novel pH sensitive biodegradable block copolymers (MPEG-PDLLA-OSM) composed of mono-methoxy poly(ethylene glycol) (MPEG), poly (D,L-lactide) (PDLLA) and sulfamethazine oligomer (OSM) were synthesized via ring-opening polymerization and a dicyclohexyl carboimide (DCC) coupling reaction. These copolymers had a relatively low critical micelle concentration (CMC) due to the strong hydrophobic properties of non-ionized OSM at pH 7.0. Also, the pH sensitive block copolymers showed the micelle-unimer transition due to the ionization-non-ionization of OSM in the pH range (pH 7.2-8.4) above the CMC. Due to the pH sensitive properties of the block copolymer, the hydrophobic drug paclitaxel (PTX) was incorporated into a pH sensitive block copolymer micelle by the pH induced micellization method, without using an organic solvent. The block copolymer micelle prepared by pH induced micellization showed a relatively high PTX loading efficiency, and good stability for 2 d at 37 degrees C. Furthermore, the PTX loaded micelle showed a sustained release of PTX with a small burst in vitro over 2 d. The present results suggest that the pH induced micellization method due to the micelle-unimer transition of the pH sensitive block copolymer would be a novel and valuable drug incorporation tool for hydrophobic and protein drugs, since no organic solvent is involved in the formulation.

Induced micellization and micellar transitions in aqueous solutions of non-linear block copolymer Tetronic® T904

“…As with other pH-sensitive copolymers, the deprotonization would be a required step for micellization [16,59,60]. The properties of the core of these micelles can strongly differ from those of the Pluronic Ò micelles since the hydrophilic diamine group connects the hydrophobic PPO chains [61].…”

Synthesis and micellization properties of triblock copolymers PDMAEMA-b-PCL-b-PDMAEMA and their applications in the fabrication of amphotericin B-loaded nanocontainers

“…CMC of block copolymers was determined by fluorescence using pyrene as a fluorescence probe, based on procedures previously reported [31,32]. Briefly, PDMAEMA-b-PCL-b-PDMAEMA micelles were prepared with various concentrations (3.8 to 8×10 −6 mg/mL) with a fixed concentration of pyrene of 0.6 μM.…”

PEO-PPO Block Copolymers for Passive Micellar Targeting and Overcoming Multidrug Resistance in Cancer Therapy

“…Active targeting can be achieved by anchoring specific ligand molecules, such as antibodies, to the shell that are selectively recognized and taken up by the targeted cell (e.g., tumor cells), tissue, or organ [25,26]. Additionally, micelles made of stimuli-responsive amphiphilic block copolymers can specifically release the content in precise sites at rates finely controlled by an external activator (e.g., ultrasounds) or by self-regulation when the microenvironmental conditions change as a consequence of the disease [27][28][29][30][31][32]. Such a gathering of features confer polymeric micelles the unique ability to perform as drug carriers capable of modifying drug pharmacokinetics and of increasing the efficacy and the safety of the treatments [22].…”