Controlled Micelle Formation and Stable Capture of Hydrophobic Drug by Alkylated POSS Methacrylate Block Copolymers

Abstract

Design of polymeric micelles, formed by self-assembly of amphiphilic block copolymers, is crucial for encapsulation of poorly soluble drugs leading to the development of promising carrier systems. Herein, we synthesized amphiphilic di-block copolymers of 2-(methacryloyloxy)ethyl phosphorylcholine (MPC) and methacrylate R-polyhedral oligomeric silsesquioxanes (POSS) (vertex R-groups of POSS cage modified with ethyl (C2H5), hexayl (C6H13), octayl (C8H17) alkyl chain) via RAFT polymerization technique. Polymeric micelle was formed in aqueous environment, and the absolute size was calculated to be around 26-43 nm. The increased alkyl chain of the R-groups of POSS led to loosely packed association of the micelles. The polymeric micelles encapsulated the hydrophobic model drugs (paclitaxel and α-tocopherol), and the encapsulation efficiency was strongly dependent on the structure of drug molecules. The drug-loaded micelles were stable for 5 days at 25 ⁰C. The release % of both the drugs from the micelles was negligible level or below 20%, suggesting the strong interaction between the R-POSS moieties and the drug molecules. Cellular uptake of the micelles by HeLa cells were quantitatively analyzed using a FITC-labelled paclitaxel (FITC-PTX). All the micelles were internalized by the cell after 2 h, and cellular uptake of PTXloaded micelle composed of the C6H13-POSS copolymer reached to the highest level, suggesting that alkyl chain length is one of the tunable factors for the cellular uptake. These diblock copolymers have great potential as hydrophobic drug carrier molecule and its delivery to specific sites.

Copolymers Composed of 2-(Methacryloyloxy)ethyl Phosphorylcholine and Methacrylated Polyhedral Oligomeric Silsesquioxane as a Simple Modifier for Liposomes

“…Here, both the random and the diblock copolymers were employed to estimate the surface coverage efficiency using the POSS and MPC sequence. We have already clarified that both the copolymers themselves were noncytotoxic as well as PMPC, 23,25 meaning that the copolymers of MPC and the methacrylated POSS are basically biocompatible and nonfouling polymers as well as the previously reported MPC-based copolymers. 18,28 Considering the biocompatible nature of the MPC and R-POSS copolymers, the liposome surface modification can provide PMPC decoration that is advantageous for overcoming PEGylation problems as mentioned before.…”

“…The mol % of R-POSS in the random copolymers were found to be 1–2 mol %. The diblock copolymers of MPC and R-POSS methacrylate (R-POSS- b- MPC 1a′ – c′ ) were prepared by RAFT polymerization technique by using poly­(2-(methacryloyloxy)­ethyl phosphorylcholine)-based chain transfer agent (PMPC 61 ). , The degree of polymerization of R-POSS part was calculated to be ca. 12. l -α-Phosphatidylcholine (HSPC) and cholesterol were purchased from Avanti Polar Lipids, Inc. (Alabama, United States).…”

“…The diblock copolymers of MPC and R-POSS methacrylate (R-POSS-b-MPC 1a′−c′) were prepared by RAFT polymerization technique by using poly(2-(methacryloyloxy)ethyl phosphorylcholine)-based chain transfer agent (PMPC 61 ). 25,29 The degree of polymerization of R-POSS part was calculated to be ca. 12.…”

“…We studied random and diblock copolymers using MPC and polyhedral oligomeric silsesquioxane (POSS) methacrylate bearing different vertex (R-) groups (ethyl (C 2 ), hexyl (C 6 ), and octyl (C 8 )) as amphiphilic polymers (Figure ). The combination of POSS and its peripheral alkyl chain moiety is a key for controlling intra- and intermolecular interaction to form colloids and solid states. − Recently, the POSS moiety was also applied as a good hydrophobic part to deliver drug molecules and/or photosensitizer. , …”

Recent progress and perspectives in applications of 2-methacryloyloxyethyl phosphorylcholine polymers in biodevices at small scales

“…The NPA may induce failures in the delivery of therapeutic agents to the desired target sites, leading to drug degradation, cell toxicity, and unexpected side reactions. To resolve the problem, copolymers composed of MPC able to suppress NPA and other moieties allowing encapsulation, delivery and controlled release of therapeutic agents have been developed to form many kinds of drug carrier structures such as nanoparticles (NPs), [115][116][117][118][119][120][121] dendrimers, 122,123 micelles, [124][125][126][127][128][129] polymersomes, [130][131][132] and liposomes 9,132,133 on micrometer to nanometer scales. The characteristics of the MPC moiety in MPC copolymers to suppress NPA can play a critical role in the improvement of the biocompatibility of the DDS by increasing blood circulation time, enhancing specific binding to the targeted cells, avoiding immune recognition and elimination, and reducing cell toxicity.…”