Nanogels are being explored as drug delivery agents for targeting cancer due to their easy tailoring properties and ability to efficiently encapsulate therapeutics of diverse nature through simple mechanisms. Nanogels are proficiently internalized by the target cells, avoid accumulating in nontarget tissues thereby lower the therapeutic dosage and minimize harmful side effects. However, there is an urgent need for relevant clinical data from nanogels so as to allow translation of the nanogel concept into a viable therapeutic application for the treatment of cancer. This review highlights some of the recent progress in nanogels as a carrier in the field of nanomedicine for the treatment of cancer. The present review critically analyzes the use of extracellular pH targeting for nanogels, siRNA delivery, PEGylated nanogels, multi-responsive nanogels and intracellular delivery of nanogels for improved therapy of cancer.
Abstract. The present investigation was aimed at developing cytarabine-loaded poly(lactide-coglycolide) (PLGA)-based biodegradable nanoparticles by a modified nanoprecipitation which would have sustained release of the drug. Nine batches were prepared as per 3 2 factorial design to optimize volume of the cosolvent (0.22-0.37 ml) and volume of non-solvent (1.7-3.0 ml). A second 3 2 factorial design was used for optimization of drug: polymer ratio (1:5) and stirring time (30 min) based on the two responses, mean particle size (125±2.5 nm), and percentage entrapment efficiency (21.8±2.0%) of the Cyt-PLGA nanoparticles. Optimized formulation showed a zeta potential of −29.7 mV indicating good stability; 50% w/w of sucrose in Cyt-PLGA NP was added successfully as cryoprotectant during lyophilization for freeze-dried NPs and showed good dispersibility with minimum increase in their mean particle sizes. The DSC thermograms concluded that in the prepared PLGA NP, the drug was present in the amorphous phase and may have been homogeneously dispersed in the PLGA matrix. In vitro drug release from the pure drug was complete within 2 h, but was sustained up to 24 h from PLGA nanoparticles with Fickian diffusion. Stability studies showed that the developed PLGA NPs should be stored in the freeze-dried state at 2-8°C where they would remain stable in terms of both mean particle size and drug content for 2 months.
A single outcome in a biological procedure at the time of cancer therapy is due to multiple changes happening simultaneously. Hence to mimic such complex biological processes, an understanding of stimuli responsiveness is needed to sense specific changes and respond in a predictable manner. Such responses due to polymers may take place either simultaneously at the site or in a sequential manner from preparation to transporting pathways to cellular compartments. The present review comprehends the stimuli-responsive polymers and multi-responsiveness with respect to cancer therapy. It focuses on the exploitation of different stimuli like temperature, pH and enzymes responsiveness in a multi-stimuli setting. Nanogels and micelles being two of the most commonly used responsive polymeric carriers have also been discussed. The role of multiple stimuli delivery system is significant due to multiple changes happening in the near surroundings of cancer cells. These responsive materials are able to mimic some biological processes and recognize at the molecular level itself to manipulate development of custom-designed molecules for targeting cancer cells.
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