Improved pH-responsive amphiphilic carboxymethyl-hexanoyl chitosan–poly(acrylic acid) macromolecules for biomedical applications

Abstract

In this communication, we report a new type of amphiphilic carboxymethyl-hexanoyl chitosan (CHC)poly(acrylic acid) (PAA) hybrid macromolecule, which was successfully prepared through polymerization of acrylic acid (AA) in the presence of amphiphilic CHC. The chemical structure of the hybrid was characterized by FT-IR and 1 H NMR, which confirmed a chemical linkage between the amine groups of CHC and hydroxyl groups of AA. This CHC-PAA hybrid exhibited amphiphilic property as the original CHC rendering the self-assembling capability to be tunable in terms of AA concentration. Compared with the existing pristine chitosan-PAA co-polymers, this CHC-PAA hybrid exhibited a relatively high pHresponsive volumetric change by 10-100 times compared with the existing alternatives reported in the literature. The hybrid nanoparticles showed excellent encapsulation efficiency greater than 90% for a hydrophobic anti-cancer substance, (S)-(+)-camptothecin. A pH-responsive drug release behavior was systematically evaluated. Besides, this hybrid also revealed excellent cytocompatibility towards the MCF-7 and BCE cell lines, which, associated with its structural stability, suggests this new type of CHC-PAA hybrid to be a promising biomaterial for oral drug delivery application.

Co-delivery nanoparticles with characteristics of intracellular precision release drugs for overcoming multidrug resistance

“…[40][41][42] Figure 3C indicates the characteristic of VCR released from outer NP at pH values of the cancer cytoplasm (pH 5.8) and blood or normal organs (pH 7.4). Under a condition of pH 5.8, the cumulative release amount of VCR released from CS-ALG@TPGS-PLGA-VCR NPs was 63.8% during 24 h and 78.6% during 60 h. Nevertheless, the cumulative release amount of VCR only was 14.9% at 24 h and 19.5% at 60 h under a condition of pH 7.4.…”

CS/PAA@TPGS/PLGA nanoparticles with intracellular pH-sensitive sequential release for delivering drug to the nucleus of MDR cells

“…4B shows the release of loaded VP-16 from inner nanoparticles (CS/PAA NPs) at pH values ranging from 4.5 to 7.4. These values represent the pH of cytoplasm (pHi, 5.8), endosomes (pHend, 6.0-6.5), lysosomes (pHl, 4.5-5.0) and the nucleus (pHn, 7.4) [25,33,34]. The results indicate that approximately 65.08% of the VP-16 is released from CS/PAA NPs at 24 h, whereas cumulative release amount of 94.32% of the VP-16 has occurred by 120 h at pH 7.4.…”

“…First, we prepared smaller drug-loaded nanoparticles [25], CS/PAA/VP-16 NPs. To do this, 2.5 mg VP-16 was dissolved in dimethyl sulfoxide (DMSO) to obtain a VP-16 solution, which was then mixed with 5 ml distilled water until the material appeared visually homogeneous.…”

pH‐Responsive Drug‐Delivery Systems

“…Of the isolated organs, the renal fluorescence intensity at 24 h after a single injection was higher than other organs ( Figure 3C). [27] Other examples of organic-materials-based pH-responsive drug-delivery systems have also been reported, including poly(b-l-malic acid), [28] poly(ethyleneimine)-poly(ethylene glycol), [29] P(2-(methacryloyloxy)-ethyl phosphorylcholine)-b-P(2-methoxy-2-oxoethyl methacrylate), [30] linear dendritic block copolymers composed of polyamidoamine dendrimer and poly(ethylene glycol) with or without galactose, [31] amphiphilic diblock copolymer that consists of a hydrophilic poly(ethylene glycol) block and a hydrophobic polymethacrylate block with acid-labile ortho ester sidechains, [32] block ionomer complexes of poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate) and cationic surfactants, [33] poly(ethylene glycol)-b-poly(l-histidine)-b-poly(l-lactic acid)-b-poly(ethylene glycol), [34] carboxymethyl dextran-coated liposomes, [35] chitosan oligosaccharide/ arachidic acid-based nanoparticles, [36] chitosan salts coated with stearic acid, [37] amphiphilic carboxymethyl-hexanoyl chitosan/poly(acrylic acid) hybrid macromolecules, [38] comb-like amphiphilic copolymers with an acetal-functionalized backbone based on poly[(2,4,6-trimethoxybenzylidene-1,1,1-tris(hydroxymethyl) ethane methacrylateco-poly(ethylene glycol) methyl ether methacrylate], [39] PEGylation of aliphatic dendritic polyester by forming acetal linkages, [40] mixed micelles of poly[(d,l-lactide)-co-glycolide)]-poly(ethylene glycol)-folate and poly(b-amino ester)-poly(ethylene glycol)-folate, [41] unimolecular micelles formed by dendritic amphiphilic block copolymers poly(amidoamine)-poly(l-lactide)-b-poly(ethylene glycol) conjugated with anti-CD105 monoclonal antibody (TRC105) and 1,4,7-triazacyclononane-N,N',N-triacetic acid (NOTA, a macrocyclic chelator for 64 Cu), [42] composite microparticle Reprinted from reference [27]. Copyright 2013 Elsevier Ltd.…”