pH and Thermal Dual-Responsive Nanoparticles for Controlled Drug Delivery with High Loading Content

Abstract

A pH and thermal dual-responsive nanocarrier with silica as the core and block copolymer composed of poly(methacrylic acid) (PMAA) and poly(N-isopropylacrylamide) (PNIPAM) as the shell was prepared by surface-initiated reversible addition–fragmentation chain-transfer (SI-RAFT) polymerization. The resulting SiO2-PMAA-b-PNIPAM particles dispersed individually in an aqueous solution at a high pH and a low temperature but reversibly agglomerated under acidic conditions or at elevated temperatures. These dual-responsive nanoparticles were used as carriers to deliver the model drug doxorubicin (DOX) with unusually high entrapment efficiency and loading content, which is due to the small size (15 nm), light weight of the cores, and high graft density (0.619 chains/nm2) achieved by SI-RAFT polymerization. The release rate was controlled by both the pH and temperature of the surrounding medium. Moreover, these particles selectively precipitated at acidic conditions with increased temperature, which may enhance their ability to accumulate at tumor sites. Cytotoxicity studies demonstrated that DOX-loaded nanoparticles are highly active against Hela cells and more effective than free DOX of an equivalent dose. A cellular uptake study revealed that SiO2-PMAA-b-PNIPAM nanoparticles could successfully deliver DOX molecules into the nuclei of Hela cells. All these features indicated that SiO2-PMAA-b-PNIPAM nanoparticles are a promising candidate for therapeutic applications.

<p>Lipid&ndash;polymer hybrid nanoparticles as a next-generation drug delivery platform: state of the art, emerging technologies, and perspectives</p>

“…[1][2][3][4] In general, these payloads are encapsulated within or covalently grafted on the surface of the nanocarriers, and after being systemically incorporated, their release is monitored by factors such as formulation of the matrix, pH of the microenvironment, and temperature of the surroudings. [5][6][7] The inherent potential of nanoparticles (NPs) for therapeutic cargo delivery is primarily attributable to few key parameters, including average nanometric size, homogeneity, surface potential, and drug loading, among others. 8,9 Surface-coated immuno-inert NPs can also skillfully bypass the reticuloendothelial system yielding increased bioavailability of encapsulated drugs.…”

Strategy to design a smart photocleavable and pH sensitive chitosan based hydrogel through a novel crosslinker: a potential vehicle for controlled drug delivery

“…6 These biomaterials comprise of composites, networks or hydrogels that respond to certain environmental stimuli viz., pH, light, temperature, redox, electric or magnetic eld, analyte concentrations. 4,7,8 Among dual stimulus-responsive drug delivery systems the most studied nanosystems are the pH and temperatureresponsive systems. [9][10][11] Other dual responsive systems studied are pH and redox-sensitive, [12][13][14] pH and magnetic responsive systems 15,16 and redox and temperature responsive nanoparticles.…”

Palladium nanoparticles-anchored dual-responsive SBA-15-PNIPAM/PMAA nanoreactor: a novel heterogeneous catalyst for a green Suzuki–Miyaura cross-coupling reaction

“…17,18 In particular, stimuliresponsive polymeric materials have been adapted under different environmental conditions, such as temperature, pH, light, and ionic strength. [19][20][21] Among the various stimuliresponsive polymers, poly(methacrylic acid) (PMAA) and poly(N-isopropyl acrylamide) (PNIPAM) have been widely studied for different applications. PMAA is considered a pHresponsive polymer, where a change in the chain conformation occurs with a change in pH.…”