The tumor-specific targeting of chemotherapeutic agents for specific necrosis of cancer cells without affecting the normal cells poses a great challenge for researchers and scientists. Though extensive research has been carried out to investigate chemotherapy-based targeted drug delivery, the identification of the most promising strategy capable of bypassing non-specific cytotoxicity is still a major concern. Recent advancements in the arena of onco-targeted therapies have enabled safe and effective tumor-specific localization through stimuli-responsive drug delivery systems. Owing to their promising characteristic features, stimuli-responsive drug delivery platforms have revolutionized the chemotherapy-based treatments with added benefits of enhanced bioavailability and selective cytotoxicity of cancer cells compared to the conventional modalities. The insensitivity of stimuli-responsive drug delivery platforms when exposed to normal cells prevents the release of cytotoxic drugs into the normal cells and therefore alleviates the off-target events associated with chemotherapy. Contrastingly, they showed amplified sensitivity and triggered release of chemotherapeutic payload when internalized into the tumor microenvironment causing maximum cytotoxic responses and the induction of cancer cell necrosis. This review focuses on the physical stimuli-responsive drug delivery systems and chemical stimuli-responsive drug delivery systems for triggered cancer chemotherapy through active and/or passive targeting. Moreover, the review also provided a brief insight into the molecular dynamic simulations associated with stimuli-based tumor targeting.

The topical route is the most appropriate route for the targeted delivery of drugs to skin tissues for the treatment of local skin diseases; however, the stratum corneum (SC), the foremost layer of the skin, acts as a major barrier. Numerous passive and active drug delivery techniques have been exploited to overcome this barrier; however, these modalities are associated with several detrimental effects which restrict their clinical applicability. Alternatively, nanotechnology-aided interventions have been extensively investigated for the topical administration of a wide range of therapeutics. In this review, we have mainly focused on the biopharmaceutical significance of polymeric nanoparticles (PNPs) (made from natural polymers) for the treatment of various topical skin diseases such as psoriasis, atopic dermatitis (AD), skin infection, skin cancer, acute-to-chronic wounds, and acne. The encapsulation of drug(s) into the inner core or adsorption onto the shell of PNPs has shown a marked improvement in their physicochemical properties, avoiding premature degradation and controlling the release kinetics, permeation through the SC, and retention in the skin layers. Furthermore, functionalization techniques such as PEGylation, conjugation with targeting ligand, and pH/thermo-responsiveness have shown further success in optimizing the therapeutic efficacy of PNPs for the treatment of skin diseases. Despite enormous progress in the development of PNPs, their clinical translation is still lacking, which could be a potential future perspective for researchers working in this field.

Background of the Study: The propose of the present work was to develop chemically cross-linked polyvinyl alcohol-co-poly(methacrylic acid) hydrogel (PVA-MAA hydrogel) for pH responsive delivery of 5-Fluorouracil (5-FU). Methods: PVA based hydrogels were prepared by free radical copolymerization. PVA has been cross-linked chemically with monomer (methacrylic acid) in aqueous medium, cross-linking agent was ethylene glycol di-methacrylate (EGDMA) and benzoyl peroxide was added as reaction initiator. 5-FU was loaded as model drug. FTIR, XRD, TGA and DSC were performed for characterization of copolymer. Surface morphology was studied by SEM. pH sensitive properties were evaluated by swelling dynamics and equilibrium swelling ratio at low and higher pH. Results: FTIR, XRD, TGA and DSC studies confirmed the formation of new copolymer. Formulations with higher MAA contents showed maximum swelling at 7.4 pH. High drug loading and higher drug release has been observed at pH 7.4. Conclusions: The current study concludes that a stable copolymeric network of PVA was developed with MAA. The prepared hydrogels were highly pH responsive. This polymeric network could be a potential delivery system for colon targeting of 5-FU in colorectal cancers.