Amphiphilic copolymer brush with random pH-sensitive/hydrophobic structure: synthesis and self-assembled micelles for sustained drug delivery

Abstract

A random hydrophobic/pH-sensitive copolymer brush poly(polylactide methacrylate-co-methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether methacrylate) [P(PLAMA-co-MAA)-b-PPEGMA] and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The polymer was synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring opening polymerization (ROP). The CMC of P(PLAMAco-MAA)-b-PPEGMA in aqueous solution was extremely low (about 1.5 mg L À1 ). The self-assembled blank and drug-loaded micelles were spherical in morphology and had an average size of 160-220 nm, determined by DLS and SEM. Ibuprofen (IBU) was selected as the model drug and encapsulated into the core of micelles via a dialysis method. The in vitro release behavior of IBU from these micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release of IBU was less than 25% of the initial drug content over 24 h, suggesting that the drug can be well protected from the harsh environment in stomach. While in simulated intestinal fluid (SIF, pH 7.4), the ionization of carboxyl groups of MAA contributed to the swelling of the micelle structure, which could accelerate the IBU release from the micelles. 35-45% of IBU was released in 8 h, 60% in 24 h, and 100% after 56 h for P(PLAMA 6.3k -co-MAA 3k )-b-PPEGMA 4k micelles, and it was 50% in 2 h, 90% in 10 h, and 100% after 14 h for P(PLAMA 6.3k -co-MAA 4.5k )-b-PPEGMA 4k micelles with an increased content of MAA. All the results indicate that the pH-sensitive P(PLAMA-co-MAA)-b-PPEGMA micelles may be a potential oral drug delivery carrier for hydrophobic drugs with sustained release.

Design and synthesis of pH-sensitive polymeric micelles for oral delivery of poorly water-soluble drugs

“…Generally, the larger the ratio of the hydrophobic core of micelle was, the lower the CMC value the micelle had, and the higher the LC and EE values of the micelle were. [13,21] However, there is an interesting phenomenon in this work, LC and EE values did not enhance with the increase in the hydrophobic segments. As seen in Table 3, the LC and EE values of P(PLAMA 10 -co-MAA 58 )-b-PAA 10 micelle, with the CMC value of 5.86 μg/mL (Table 2), reached to 6.7 and 26.2%, much higher than values of P(PLAMA 10 -co-MAA 45 )-b-PAA 10 and P(PLAMA 20 -co-MA-A 58 )-b-PAA 10 micelles.…”

“…Poly(acrylic acid) (PAA) and poly(methacrylic acid) (PMAA), bearing the carboxylic group with pKa around 5−6, are the two representative and frequently pH-sensitive polymers used in oral drug delivery. [12,13] They are commonly accepted as bioadhesive and safe polymers, as the ionic carboxyl of PAA or PMAA in the micellar corona can facilitate mucoadhesion. Some researchers have exploited pH-sensitive polymeric micelles containing these moieties for improving oral bioavailability of poorly water-soluble drugs.…”

A branched polymer as a pH responsive nanocarrier: Synthesis, characterization and targeted delivery

“…The PE-PCL-b-P t BA was synthesized by ATRP [47]. The structure of the branched block copolymer is recognized by 1 H NMR spectrum (displayed in Fig.…”

Poly(2-(diethylamino)ethyl methacrylate)-based, pH-responsive, copolymeric mixed micelles for targeting anticancer drug control release

“…With the increase in the copolymer concentration, the emission of pyrene probe was shifted from 336 to 338 nm. 35 The intensity ratio of I 338 /I 336 of the polymer in various concentrations is shown in Figure 3 To study the pK b buffer range of the copolymers in aqueous solution, acid-base titration was conducted with an automatic titrator (Hanon T-860; Hanon Instruments, Jinan, China). The PDEAEMA block in the copolymers was a weak polybase, resulting in a pH buffering capability of the copolymers.…”