Synthesis and Physicochemical Characterization of Amphiphilic Triblock Copolymer Brush Containing pH-Sensitive Linkage for Oral Drug Delivery

Abstract

A novel and well-defined pH-sensitive amphiphilic triblock copolymer brush poly(lactide)-b-poly(methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) (PLA-b-PMAA-b-PPEGMA) and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The copolymer and its precursors were synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring-opening polymerization (ROP) techniques. The molecular structures and characteristics were confirmed by GPC, (1)H NMR, and FT-IR. The critical micelle concentration (CMC) values of PLA-b-PMAA-b-PPEGMA in aqueous medium varied from 1.4 to 2.6 mg/L, and the partition equilibrium constant (K(v)) of pyrene in micellar solutions ranged from 2.873 × 10(5) to 3.312 × 10(5). The average sizes of the self-assembled blank and drug-loaded micelles were 140-250 nm determined by DLS in aqueous solution. The morphology of the micelles was found to be spherical by SEM. Nifedipine (NFD), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. The in vitro release behavior of NFD from the micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release percent of NFD was relative low, while in simulated intestinal fluid (SIF, pH 7.4), more than 96% was released within 24 h. All the results showed that the pH-sensitive PLA-b-PMAA-b-PPEGMA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior.

Co-Delivery of Imiquimod and Plasmid DNA via an Amphiphilic pH-Responsive Star Polymer that Forms Unimolecular Micelles in Water

“…We then presented another 1 H NMR spectra, which clearly showed characteristic chemical shifts of protons in the prepolymers and final polymer products (Figure 2). Through integrating the areas of characteristic peaks including the end-groups, the degree of polymerization (DP) of each block and molecular weight of the polymer product were estimated [47,48]. (1) DP PLA = I a /I a' (1)…”

Structure–property relationship of pH‐sensitive (PCL)2(PDEA‐b‐PPEGMA)2 micelles: Experiment and DPD simulation

“…[1][2][3][4] Especially, the pH-sensitive micelles currently have attracted much attention as smart drug delivery systems for cancer therapy. An ideal anticancer pH-sensitive micelle can remain stable in normal tissues (pH 7.4) while release drugs rapidly in tumoral conditions (pH 5.0).…”

Polymeric micelles for oral drug administration enabling locoregional and systemic treatments

“…One strategy to prevent GI degradation and/or to promote drug absorption across the intestine is the development of pH-sensitive polymeric micelles, which protect the drug from the gastric environment but ensure complete release during intestinal transit [1,12,117,118]. These systems are based on either dissociation or destabilization (via collapse or swelling) of the micelle upon changes in pH, or pH-dependent changes in partition coefficient between the drug and the micelle.…”