A B S T R A C TRheumatoid arthritis (RA) is the most common complex multifactorial joint related autoimmune inflammatory disease with unknown etiology accomplished with increased cardiovascular risks. RA is characterized by the clinical findings of synovial inflammation, autoantibody production, and cartilage/bone destruction, cardiovascular, pulmonary and skeletal disorders. Pro-inflammatory cytokines such as IL-1, IL-6, IL-8, and IL-10 were responsible for the induction of inflammation in RA patients. Drawbacks such as poor efficacy, higher doses, frequent administration, low responsiveness, and higher cost and serious side effects were associated with the conventional dosage forms for RA treatment. Nanomedicines were recently gaining more interest towards the treatment of RA, and researchers were also focusing towards the development of various anti-inflammatory drug loaded nanoformulations with an aid to both actively/passively targeting the inflamed site to afford an effective treatment regimen for RA. Alterations in the surface area and nanoscale size of the nanoformulations elicit beneficial physical and chemical properties for better pharmacological activities. These drug loaded nanoformulations may enhances the solubility of poorly water soluble drugs, improves the bioavailability, affords targetability and may improve the therapeutic activity. In this regimen, the present review focus towards the novel nanoparticulate formulations (nanoparticles, nanoemulsions, solid lipid nanoparticles, nanomicelles, and nanocapsules) utilized for the treatment of RA. The recent advancements such as siRNA, peptide and targeted based nanoparticulate systems for RA treatment were also discussed. Special emphasis was provided regarding the pathophysiology, prevalence and symptoms towards the development of RA.

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Stimuli responsive nanocarriers are gaining much attention due to its versatile multifunctional activities including disease diagnosis and treatment. Recently, clinical applications of nano drug delivery systems for cancer treatment make a considerable challenge due to its limited cellular uptake, low bioavailability, poor targetability, stability issues, and unfavourable pharmacokinetics. To overcome these issues researchers are focussing on stimuli responsive systems. Nano carriers elicit its role through endogenous (pH, temperature, enzyme and redox) or exogenous (temperature, light, magnetic field, ultrasound) stimulus. These systems were designed to overcome the shortcomings such as non-specificity and toxicity associated with the conventional drug delivery systems. The pH variation between healthy cells and tumor microenvironment creates a platform towards the generation of pH sensitive nano delivery systems. Herein, we propose to present an overview of various internal and external stimuli responsive behavior based drug delivery systems. Herein the present review will focus specifically on the significance of various pH- responsive nanomaterials such as polymeric nanoparticles, nano micelles, inorganic based pH sensitive drug delivery carriers such as calcium phosphate nanoparticles, and carbon dots in cancer treatment. Moreover, this review elaborates the recent findings on pH based stimuli responsive drug delivery system with special emphasis towards our reported stimuli responsive systems for cancer treatment.

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