The Smart Drug Delivery of Rotigotine Using Transdermal Patch for the Successful Management of Parkinson's Disease.

BACKGROUND: A Non-Ergot Dopamine Agonist (NEDA) rotigotine has been designed as a new transdermal drug delivery system. AIM: To maintain optimum homogeneity in drug content, the rotigotine transdermal patch was developed utilizing a solvent casting technique. METHODS: The characteristics of a transdermal patch, including patch weight, folding endurance, patch thickness, surface morphology, tensile strength, swelling rate, surface pH, in vitro release studies, water retention rate, uniformity of drug content, and ex-vivo permeation studies, were determined. RESULTS: In vitro drug release studies unequivocally demonstrated that drug release controlled polymer interactions. There was no apparent lag period before the drug release rate started to decline. The developed patch showed 70 ± 1.18 % of prolongation of drug release within 24 hours. The result of the penetration studies demonstrated that 61 ± 2.52% of rotigotine permeated through the epidermal barrier within 24 h. CONCLUSION: The developed transdermal patch comprising rotigotine was evidently placed on the dermis layer, and an appropriate dose was delivered into circulation for a longer time based on the aforementioned factors. The findings of this study illustrate the effective approach of transdermal patches to treat Parkinson's disease.

Microbiome and the inflammatory pathway in peri-implant health and disease with an updated review on treatment strategies.

Crestal bone preservation around the dental implant for aesthetic and functional success is widely researched and documented over a decade. Several etiological factors were put forth for crestal bone loss; of which biofilm plays a major role. Biofilm is formed by the colonization of wide spectra of bacteria inhabited around dental implants. Bacterial adherence affects the regulators of bone growth and an early intervention preserves the peri-implant bone. Primary modes of therapy stated in early literature were either prevention or treatment of infection caused by biofilm. This narrative review overviews the microbiome during different stages of peri-implant health, the mechanism of bone destruction, and the expression of the biomarkers at each stage. Microbial contamination and the associated biomarkers varied depending on the stage of peri-implant infection. The comprehensive review helps in formulating a research plan, both in diagnostics and treatment aspects in improving peri-implant health.

Nanoformulations - Insights Towards Characterization Techniques.

BACKGROUND: Drug-loaded novel nanoformulations are gaining importance due to their versatile properties compared to conventional pharmaceutical formulations. Nanomaterials, apart from their multifactorial benefits, have a wider scope in the prevention, treatment, and diagnosis of cancer. Understanding the chemistry of drug-loaded nano-formulations to elicit its behaviour both at molecular and systemic levels is critical in the present scenario. Drug-loaded nanoformulations are controlled by their size, shape, surface chemistry, and release behavior. The major pharmaceutical drug loaded nanocarriers reported for anticancer drug delivery for the treatment of various forms of cancers such as lung cancer, liver cancer, breast cancer, colon cancer, etc include nanoparticles, nanospheres, nanodispersions, nanocapsules, nanomicelles, cubosomes, nanoemulsions, liposomes and niosomes. The major objectives in designing anticancer drug-loaded nanoformulations are to manage the particle size/morphology correlating with the drug release to fulfil the specific objectives. Hence, nano characterizations are very critical both at in vitro and in vivo levels. OBJECTIVE: The main objective of this review paper is to summarise the major characterization techniques used for the characterization of drug-loaded nanoformulations. Even though information on characterization techniques of various nano-formulations is available in the literature, it is scattered. The proposed review will provide a comprehensive understanding of nanocharacterization techniques. CONCLUSION: To conclude, the proposed review will provide insights towards the different nano characterization techniques along with their recent updates, such as particle size, zeta potential, entrapment efficiency, in vitro release studies (chromatographic HPLC, HPTLC, and LC-MS/MS analysis), EPR analysis, X-ray diffraction analysis, thermal analysis, rheometric, morphological analysis etc. Additionally, the challenges encountered by the nano characterization techniques will also be discussed.

Current Drug Targeting using siRNA-based Nano Therapeutics for Pulmonary Diseases.

The importance of siRNA in nano drug delivery systems to target important pulmonary disorders, such as chronic obstructive pulmonary disease (COPD), asthma, lung cancer, and others, is reviewed in this perspective. The great majority of lung illnesses are caused by protein misfolding. As a result, siRNA-based therapies are increasingly being used to target the gene. Given the difficulties of delivering bare siRNA, siRNA protection may ensure its efficacy in gene therapy. These issues could be solved with a nano-based siRNA delivery systems. In this context, a siRNA-based nanocarrier for major pulmonary disorders has been explored.

Guar gum based oral films for hypertensive urgencies.

Guar gum (GG) is a natural film forming biopolymer used as a drug delivery media for Telmisartan (TS). TS is a poorly water-soluble anti-hypertensive agent with low bioavailability.The present work has been hypothesized by converting TS into nanocrystals by high shear homogenisation to enhance the solubility thereby the bioavailability is expected to get enhanced. TS-NC-GG-OF was formulated by solvent casting method using GG by varying the disintegrant ratio.Telmisartan nanocrystals showed particle size of 441.70 ± 35.28 nm, surface charge of -20.86 ± 0.55 mV and reduced crystalline pattern. The amount of TS present per mg ofnanocrystals is 0.33 mg. The developed TS-NC-GG-OF was circular, creamy white colour with desired physicochemical properties. The in vitro release studies performed by beaker model showed an immediate release pattern.This proof of concept specifies that the TS-NC-GG-OF may be a better choice for hypertensive emergencies using the natural excipient Guar gum.

Development and Evaluation of Polyvinylpyrrolidone K90 and Poloxamer 407 Self-Assembled Nanomicelles: Enhanced Topical Ocular Delivery of Artemisinin.

Age-related macular degeneration is a multifactorial disease affecting the posterior segment of the eye and is characterized by aberrant nascent blood vessels that leak blood and fluid. It ends with vision loss. In the present study, artemisinin which is poorly water-soluble and has potent anti-angiogenic and anti-inflammatory properties was formulated into nanomicelles and characterized for its ocular application and anti-angiogenic activity using a CAM assay. Artemisinin-loaded nanomicelles were prepared by varying the concentrations of PVP k90 and poloxamer 407 at different ratios and showed spherical shape particles in the size range of 41-51 nm. The transparency and cloud point of the developed artemisinin-loaded nanomicelles was found to be 99-94% and 68-70 °C, respectively. The in vitro release of artemisinin from the nanomicelles was found to be 96.0-99.0% within 8 h. The trans-corneal permeation studies exhibited a 1.717-2.169 µg permeation of the artemisinin from nanomicelles through the excised rabbit eye cornea for 2 h. Drug-free nanomicelles did not exhibit noticeable DNA damage and showed an acceptable level of hemolytic potential. Artemisinin-loaded nanomicelles exhibited remarkable anti-angiogenic activity compared to artemisinin suspension. Hence, the formulated artemisinin-loaded nanomicelles might have the potential for the treatment of AMD.

Recent Progress in Stimuli-Responsive Intelligent Nano Scale Drug Delivery Systems: A Special Focus Towards pH-Sensitive Systems.

Stimuli-responsive nanocarriers are gaining much attention due to their versatile multifunctional activities, including disease diagnosis and treatment. Recently, clinical applications of nano-drug delivery systems for cancer treatment pose a challenge due to their limited cellular uptake, low bioavailability, poor targetability, stability issues, and unfavourable pharmacokinetics. To overcome these issues, researchers are focussing on stimuli-responsive systems. Nanocarriers elicit their 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 for 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 systems with special emphasis on our reported stimuli-responsive systems for cancer treatment.

Combinatorial analysis of quercetin and resveratrol by HPTLC in Sesbania grandiflora/phyto-based nanoformulations.

A sensitive HPTLC method was developed for the simultaneous estimation of quercetin (QUR) and resveratrol (RES). The chromatographic separation was achieved using mobile phase toluene:chloroform:ethyl acetate:formic acid (3:2:4.9:0.1% v/v) and densitometric scan performed at 280 nm. The developed method was linear at 2-10 µg/mL with correlation coefficient of 0.9907 (QUR) and 0.9917 (RES). The method was validated for its precision, specificity, detection and quantification limits and % RSD was found to be less than 4.0%. The developed HPTLC method was evaluated in QUR and RES-loaded nanoformulation and Sesbania grandiflora leaf extract. The amount of QUR and RES present in the SG leaf extract was found to be 26.13 ± 0.7 µg/mg and 4.31 ± 0.8 µg/mg, respectively. The pH-dependent stability of RES has checked using the developed method. The above-developed method can be used to check the QUR/RES content in herbal/pharmaceutical formulation with scope towards industries.

Solubility Enhancement of Methotrexate by Solid Nanodispersion Approach for the Improved Treatment of Small Cell Lung Carcinoma.

AIMS: The present work aimed to develop MT loaded solid Nano dispersion by improving its solubility, half-life and bioavailability in biological system thereby this formulation may be afforded economically. BACKGROUND: Small cell lung carcinoma is a type of malignant tumor characterized by uncontrolled cell growth at lung tissues. The potent anti-cancer drug methotrexate (MT) chosen for the present work is poorly soluble in water (BCS type IV class) with short half-life and hepatotoxic effect. OBJECTIVE: With the concept of polymeric surfactant to improve the solubility along with wettability of drugs, the present work has been hypothesized to improve its solubility using polyvinyl pyrollidone (PVP K30) polymer and α- tocopheryl polyethylene glycol 1000 succinate (TPGS) surfactant, thereby the bioavailability is expected to get enhanced. By varying the PVP K30 and TPGS ratios different formulations were developed using emulsification process. METHODS: The developed MT loaded solid nanodispersion was further characterized for its particle size, charge, morphology, encapsulation efficiency and in-vitro release behavior etc. Results: The results of FT-IR spectrometric analysis indicated the compatibility nature of MTX, PVPK30 and TPGS. The developed formulations showed spherical morphology, particle size ranging from 59.28±24.2 nm to 169.33±10.85 nm with a surface charge ranging from -10.33 ± 2.81mV to -9.57 ± 1.2 mV. The in vitro release studies as performed by dialysis bag method showed a sustained release pattern as checked by UV Spectrophotometer. Residual solvent analysis for MTXNDs performed by HPLC indicates there is no residual DMSO in the formulation. Transmission electron microscopic image of MTXNDs revealed that the particles are spherical shaped with a solid core structure. Haemolytic assay indicates that the developed formulation is safe for intravenous administration. Cell culture studies in A549 cells indicates the enhanced cytotoxic effect for the developed formulation. CONCLUSION: This proof of study indicates that the developed formulation may have anticancer potential for SCLC treatment.

In vivo synergistic anti-tumor effect of lumefantrine combined with pH responsive behavior of nano calcium phosphate based lipid nanoparticles on lung cancer.

Conventional treatment options for lung cancer treatment were restricted due to non-specific nature and side effects, with this associated problem and to overcome this we had developed lumefantrine with nano calcium phosphate loaded lipid nanoparticles (LF- CaP- Ls) affording pH sensitive mechanism. Herein, the present study the in vivo anti-cancer property of LF-CaP-Ls was checked in mice models. Further, reduced lung cancer progression of lumefantrine with nano calcium phosphate loaded lipid nanoparticles (LF-CaP-Ls) treated mice were assessed by measuring the 5-methyltetrahydrofolate (MTHF) in serum. Moreover, LF-CaP-Ls showed substantially a anticancer effect compared to that of lumefantrine loaded lipid nanoparticles (LF-Ls) and free lumefantrine (LF) by exhibiting higher effects in lung tumor bearing mice model as confirmed by reduced tumor progression. Histopathological examination of lungs supported with H&E staining proved the reduced tumor vasculature and reduced inflammatory cells for LF-CaP-Ls compared to that of free LF and LF-Ls. Further, visual inspection with acetic acid test confirmed the reduced tumor progression for LF-CaP-Ls compared to that of free LF and LF-Ls. Altogether, the overall results suggested that the developed LF-CaP-Ls may acts as a better therapeutic molecule for lung cancer due to its maintenance of increased level of 5-MTHF levels, reduced tumor weight. Further, hematological and biochemical parameters were measured and supports our in-vivo therapeutic effect of LF-CaP-Ls.

Anti-platelet Drug-loaded Targeted Technologies for the Effective Treatment of Atherothrombosis.

Atherothrombosis results from direct interaction between atherosclerotic plaque and arterial thrombosis and is the most common type of cardiovascular disease. As a long term progressive disease, atherosclerosis frequently results in an acute atherothrombotic event through plaque rupture and platelet-rich thrombus formation. The pathophysiology of atherothrombosis involves cholesterol accumulation endothelial dysfunction, dyslipidemia, immuno-inflammatory, and apoptotic aspects. Platelet activation and aggregation is the major cause for stroke because of its roles, including thrombus, contributing to atherosclerotic plaque, and sealing off the bleeding vessel. Platelet aggregates are associated with arterial blood pressure and cardiovascular ischemic events. Under normal physiological conditions, when a blood vessel is damaged, the task of platelets within the circulation is to arrest the blood loss. Antiplatelet inhibits platelet function, thereby decreasing thrombus formation with complementary modes of action to prevent atherothrombosis. In the present scientific scenario, researchers throughout the world are focusing on the development of novel drug delivery systems to enhance patient's compliance. Immediate responding pharmaceutical formulations become an emerging trend in the pharmaceutical industries with better patient compliance. The proposed review provides details related to the molecular pathogenesis of atherothrombosis and recent novel formulation approaches to treat atherothrombosis with particular emphasis on commercial formulation and upcoming technologies.

The Role of Nano-ophthalmology in Treating Dry Eye Disease.

Dry eye disease (DED) is a common multifactorial disease linked to the tears/ocular surface leading to eye discomfort, ocular surface damage, and visual disturbance. Antiinflammatory agents (steroids and cyclosporine A), hormonal therapy, antibiotics, nerve growth factors, essential fatty acids are used as treatment options of DED. Current therapies attempt to reduce the ocular discomfort by producing lubrication and stimulating gland/nerve(s) associated with tear production, without providing a permanent cure for dry eye. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. This review presents an overview, pathophysiology, prevalence and etiology of DED, with an emphasis on preclinical and clinical studies involving the use of nanocarrier systems in treating DED. Lay Summary: Dry eye disease (DED) is a multifactorial disease associated with tear deficiency or excessive tear evaporation. There are several review articles that summarize DED, disease symptoms, causes and treatment approaches. Nanocarrier systems show a great promise to revolutionize drug delivery in DED, offering many advantages such as site specific and sustained delivery of therapeutic agents. Very few review articles summarize the findings on the use of nanotherapeutics in DED. In this review, we have exclusively discussed the preclinical and clinical studies of nanotherapeutics in DED therapy. This information will be attractive to both academic and pharmaceutical industry researchers working in DED therapeutics.

Novel Nanocarriers for the Treatment of Wound Healing.

The sequence of biochemical and cellular responses restoring the integrity of the subcutaneous tissue of the skin is termed as wound healing. Inflammatory cytokine suppression and inflammatory transduction cascades are the major targets for wound healing. Formulations for wound healing should promote neovascularization and angiogenic pathways by increasing the expression of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor. Medication used for wound healing promotes antiinflammatory associated with anti-bacterial action. In order to boost the effectiveness of current medical treatments, the cutting-edge nanotechnology offers many novel therapies. This review summarized and discussed wound healing, types of wounds, natural materials used for wound healing, metallic nanoparticles and current nano drug delivery systems used for wound healing with special emphasis on the angiogenesis role in the healing of wounds.

Correction to: Development of Methotrexate and Minocycline Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis.

Typesetting error occurred and author corrections to the numbering of figures and captions at the proofing stage were not incorporated in the published article.

Development of Methotrexate and Minocycline Loaded Nanoparticles for the Effective Treatment of Rheumatoid Arthritis.

Rheumatoid arthritis is an autoimmune disease that leads to cartilage destruction, synovial joint inflammation, and bacterial joint/bone infections. In the present work, methotrexate and minocycline-loaded nanoparticles (MMNPs) were developed with an aim to provide relief from inflammation and disease progression/joints stiffness and to control the bacterial infections associated with rheumatoid arthritis. MMNPs were developed and optimized by solvent evaporation along with high-pressure homogenization technique using poly(lactic-co-glycolic acid) (50:50%) copolymer. FTIR spectrometric results showed the compatibility nature of methotrexate, minocycline, and poly(lactic-co-glycolic acid). The MMNPs showed particle size ranging from 125.03 ± 9.82 to 251.5 ± 6.23 nm with charge of around - 6.90 ± 0.8 to - 34.8 ± 4.3 mV. The in vitro release studies showed a sustained release pattern with 75.11% of methotrexate (MTX) release and 49.11% of minocycline hydrochloride (MNC) release at 10 h. The developed MMNPs were found to be stable at refrigerated condition and non-hemolytic nature (< 22.0%). MMNPs showed superior cytotoxicity for studied concentrations (0.1 to 1000 µM) compared with free MTX at both 24 and 48 h treatment period in a dose/time-dependent manner in inflammatory RAW 264.7 cells. Anti-bacterial studies indicate that the efficacy of the developed MMNPs to control infections was compared with pure MNC. In vivo anti-arthritis showed effective arthritis reduction potential of the developed MMNPs upon intravenous administration. This proof of concept implies that MTX with MNC combined nanoparticles may be effective to treat RA associated with severe infections. Graphical abstract.

Design and development of artemisinin and dexamethasone loaded topical nanodispersion for the effective treatment of age-related macular degeneration.

Age-related macular degeneration (AMD) is a disease affecting the macula by the new blood vessels formation. AMD is widely treated with a combination of anti-angiogenic and anti-vascular endothelial growth factor (VEGF) agents. The topical administration of nanodispersions showed enhanced ocular residence time with controlled and prolonged drug delivery to the disease site at the back of the eye. In the present study we developed and characterized nanodispersion containing anti-angiogenic (artemisinin) and anti-VEGF agent (dexamethasone) for the topical ocular administration in order to obtain a required drug concentration in the posterior part of the eye. The nanodispersions were prepared with varying concentration of polymer, polyvinyl pyrrolidone K90 and polymeric surfactant, Poloxamer 407. The nanodispersions were found to be smooth and spherical in shape with a size range of 12-26 nm. In-vitro drug release studies showed the 90-101% of artemisinin and 55-103% of dexamethasone release from the nanodispersions. The blank formulation with a high concentration of polymer and polymeric surfactant showed an acceptable level of haemolysis and DNA damage. The chorioallantoic membrane assay suggested that the nanodispersion possess good anti-angiogenic effect. Hence the formulated artemisinin and dexamethasone nanodispersion may have the great potential for the AMD treatment.

pH responsive delivery of lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the site specific treatment of lung cancer.

The present work aim to develop pH responsive nanosystem comprising lumefantrine with calcium phosphate nanoparticles loaded lipidic cubosomes for the effective treatment of lung cancer. FTIR results showed that, compatibility nature of selected excipients for the synthesis of LF-CaP-Cs. The XRD results showed developed LF-CaP-Cs were non crystalline in nature. The selected developed LF-CaP-Cs were in cubic phase with average particle size of 259.4 ± 19 nm with a charge of -2.28 ± 0.7 mV. The encapsulation efficiency for LF within LF-CaP-Cs was about 78.76 ± 0.5%. RP-HPLC analysis showed that LF release rate gets significantly enhanced with higher peak area at pH 4.0 compared to pH 5.0/pH 7.4. The in-vitro release of LF-CaP-Cs showed that LF release gets significantly increased at pH 4.0 (84.04 ± 0.4%) compared to pH 7.4 (48.32 ± 1.6%) at 12 h. Further, CAM assay showed the superior anti-angiogenesis potential of developed LF-CaP-Cs compared to LF-Cs/blank Cs. The cytotoxicity effect of LF-CaP-Cs (28 ± 1.8 µg/mL) was significantly higher than that of free LF (40 ± 0.9 µg/mL). The results of cellular uptake study proved the localization of LF at cellular level and AO/EB staining results revealed that the A549 cell undergoes apoptosis in A549 cells.

Biological macromolecules for ophthalmic drug delivery to treat ocular diseases.

Development of newer drug carrier systems by the researchers has resulted in numerous breakthroughs in the development and manufacturing of ocular products. The ocular bioavailability of drugs at the posterior segment of the eye is a challenging task in the present scenario. Naturally derived macromolecular carriers are widely used to increase the efficacy of ocular drugs. They provide enhanced corneal permeability and retention effect at the surface of cornea for a prolonged period of time. In this regimen the present review focuses towards the major ocular diseases and their prevalence and development of efficient drug carrier systems utilizing various naturally derived macromolecules for improved delivery of drugs to treat ocular diseases.

Tannic acid attenuates TGF-ß1-induced epithelial-to-mesenchymal transition by effectively intervening TGF-ß signaling in lung epithelial cells.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and an irreversible lung disorder characterized by the accumulation of fibroblasts and myofibroblasts in the extracellular matrix. The transforming growth factor-ß1 (TGF-ß1)-induced epithelial-to-mesenchymal transition (EMT) is thought to be one of the possible sources for a substantial increase in the number of fibroblasts/myofibroblasts in IPF lungs. Tannic acid (TA), a natural dietary polyphenolic compound has been shown to possess diverse pharmacological effects. However, whether TA can inhibit TGF-ß1-mediated EMT in lung epithelial cells remains enigmatic. Both the human adenocarcinomic alveolar epithelial (A549) and normal bronchial epithelial (BEAS-2B) cells were treated with TGF-ß1 with or without TA. Results showed that TA addition, markedly inhibited TGF-ß1-induced EMT as assessed by reduced expression of N-cadherin, type-1-collagen, fibronectin, and vimentin. Furthermore, TA inhibited TGF-ß1-induced cell proliferation through inducing cell cycle arrest at G0/G1 phase. TGF-ß1-induced increase in the phosphorylation of Smad (Smad2 and 3), Akt as well as that of mitogen activated protein kinase (ERK1/2, JNK1/2, and p38) mediators was effectively inhibited by TA. On the other hand, TA reduced the TGF-ß1-induced increase in TGF-ß receptors expression. Using molecular docking approach, FTIR, HPLC and Western blot analyses, we further identified the direct binding of TA to TGF-ß1. Finally, we conclude that TA might directly interact with TGF-ß1, thereby repressing TGF-ß signaling and subsequent EMT process in lung epithelial cells. Further animal studies are needed to clarify its potential therapeutic benefit in pulmonary fibrosis.

Novel nano therapeutic materials for the effective treatment of rheumatoid arthritis-recent insights.

Rheumatoid 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.