Neuromodulatory potential of phenylpropanoids; para-methoxycinnamic acid and ethyl-p-methoxycinnamate on aluminum-induced memory deficit in rats.

Para-methoxycinnamic acid (PMCA) and Ethyl-p-methoxycinnamate (EPMC) are reported to possess neuroprotective effect in reversing an acute memory deficit. However, there is a dearth of evidence for their therapeutic effect in chronic memory deficit. Thus, there is a scope to study these derivatives against the chronic model of cognitive dysfunction. The present study was aimed to determine the cognitive enhancing activity of PMCA and EPMC in aluminum-induced chronic dementia. Cognitive enhancing property of PMCA and EPMC was assessed using Morris water maze by analyzing spatial memory parameters such as escape latency, D-quadrant latency, and island entries. To find a possible mechanism, the effect of test compounds on altered acetylcholinesterase (AChE) activity and oxidative stress was determined in the hippocampus and frontal cortex of rats. Docking interaction of these derivatives with acetylcholinesterase enzyme and glutamate receptors was also studied. Treatment with PMCA and EPMC showed a significant improvement in spatial memory markers and altered hippocampal AChE activity in rats with cognitive dysfunction. The implication of hippocampal and cortical oxidative stress in memory impairment was confirmed with decreased catalase/increased thiobarbituric acid reactive substances (TBARS) in rats. PMCA and EPMC reversed the oxidative stress in the brain by negatively affecting TBARS levels. Against depleted catalase levels, PMCA was more effective than EPMC in raising the depleted catalase levels. In silico analysis revealed poor affinity of EPMC and PMCA with AChE enzyme and glutamate receptor. To conclude, PMCA and EPMC exerted cognitive enhancing property independent of direct AChE and glutamate receptor inhibition.

Investigation of sesamol on myeloperoxidase and colon morphology in acetic acid-induced inflammatory bowel disorder in albino rats.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of gastrointestinal tract of immune, genetic, and environmental origin. In the present study, we examined the effects of sesamol (SES), which is the active constituent of sesame oil in the acetic acid (AA) induced model for IBD in rats. METHODS: The groups were divided into normal control, AA control, SES, and sulfasalazine (SS). On day 7, the rats were killed, colon was removed, and the macroscopic, biochemical, and histopathological evaluations were performed. RESULTS: The levels of MPO, TBARS, and tissue nitrite increased significantly (P < 0.05) in the AA group whereas they reduced significantly in the SES and SS treated groups. Serum nitrite levels were found to be insignificant between the different groups. CONCLUSIONS: The mucosal protective effects of sesamol in IBD are due to its potential to reduce the myeloperoxidase and nitrite content.

Toxicological evaluation of Terminalia paniculata bark extract and its protective effect against CCl4-induced liver injury in rodents.

BACKGROUND: Based on the reported antioxidant and anti-inflammatory potential of Terminalia paniculata, the bark aqueous extract (TPW) was investigated against liver damage. METHODS: Intrinsic cytotoxicity was tested on normal human liver (Chang) cell lines, followed by acute and sub-chronic toxicity studies in mice. TPW was then evaluated against CCl4-induced liver toxicity in rats. Liver enzymes (AST, ALT, and ALP) and antioxidant markers were assessed. The effect of TPW on isolated hepatic cells, post-CCl4 administration, was assessed by isolated mitochondrial membrane staining. The actions of TPW on apoptotic pathway in CCl4-treated Chang cells were also elucidated. RESULTS: TPW was found to be safe at all doses tested in both in vitro and in vivo toxicity studies. TPW (400 mg/kg, p.o.) significantly (*p <0.05) improved liver enzyme activity as compared to CCl4. Also, it improved antioxidant status (GSH, GST, MDA and total thiol) and preserved hepatic cell architecture. TPW pre-treatment significantly attenuated the levels of phospho-p53, p53, cleaved caspase-3, phospho-Bad, Bad and cleaved PARP in CCl4-treated Chang cells, improving the viability considerably. CONCLUSION: The findings support a protective role for Terminalia paniculata in pathologies involving oxidative stress.

Emphasizing roles of BDNF promoters and inducers in Alzheimer's disease for improving impaired cognition and memory.

Brain-derived neurotrophic factor (BDNF) is a crucial neurotrophic factor adding to neurons' development and endurance. The amount of BDNF present in the brain determines susceptibility to various neurodegenerative diseases. In Alzheimer's disease (AD), often it is seen that low levels of BDNF are present, which primarily contributes to cognition deficit by regulating long-term potentiation (LTP) and synaptic plasticity. Molecular mechanisms underlying the synthesis, storage and release of BDNF are widely studied. New molecules are found, which contribute to the signal transduction pathway. Two important receptors of BDNF are TrkB and p75NTR. When BDNF binds to the TrkB receptor, it activates three main signalling pathways-phospholipase C, MAPK/ERK, PI3/AKT. BDNF holds an imperative part in LTP and dendritic development, which are essential for memory formation. BDNF supports synaptic integrity by influencing LTP and LTD. This action is conducted by modulating the glutamate receptors; AMPA and NMDA. This review paper discusses the aforesaid points along with inducers of BDNF. Drugs and herbals promote neuroprotection by increasing the hippocampus' BDNF level in various disease-induced animal models for neurodegeneration. Advancement in finding pertinent molecules contributing to the BDNF signalling pathway has been discussed, along with the areas that require further research and study.

Diabetic wound healing approaches: an update.

Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.

Dehydrozingerone promotes healing of diabetic foot ulcers: a molecular insight.

INTRODUCTION: One of the most common problems of diabetes are diabetic foot ulcers (DFUs). According to National Institute for Health, initial management of DFUs can decrease the complication of limb amputations and can improve the patient's quality of life. DFU treatment can be optimized with the help of multidisciplinary approach. Based on many studies, control of glucose levels in blood, antioxidant activity, reduction in cytokine levels, re-epithelialization, collagen formation, migration of fibroblasts are major phases involved in managing DFU. Dehydrozingerone (DHZ), has been known for its anti-inflammatory, antioxidant and wound healing properties. METHODOLOGY: Three months high-fat diet and low dose of streptozotocin-induced type-II diabetic foot ulcer model was used to evaluate the effectiveness of dehydrozingerone. DHZ was given orally to rats for 15 days post wounding. TNF-α, IL-1ß and antioxidant parameters like lipid peroxidation, glutathione reductase were estimated. Immunoblotting was done to investigate the effect of DHZ on the expression of ERK, JNK, HSP-27, P38, SIRT-1, NFκB, SMA, VEGF and MMP-9 in skin tissue. Histopathology was performed for analyzing DHZ effect on migration of fibroblasts, formation of epithelium, granulation tissue formation, angiogenesis and collagen formation. RESULTS: DHZ decreased the levels of malondialdehyde, TNF-α, IL-1ß and increased glutathione levels in wound tissue. Western blotting results suggested that DHZ activated ERK1/2/JNK/p38 signaling, increased expression of HSP-27, SIRT-1, VEGF, SMA thus facilitating the migration and proliferation of fibroblasts, angiogenesis and decreased inflammation. Masson Trichrome & histopathology showed an increase in collagen, epithelial and granulation tissue formation. CONCLUSION: DHZ significantly accelerates the healing of diabetic foot ulcers in high fat diet fed plus low dose streptozotocin induced type-II diabetic Wistar rats.

Nanoparticle-mediated active and passive drug targeting in oral squamous cell carcinoma: current trends and advances.

Oral squamous cell carcinoma (OSCC) is an invasive and highly malignant cancer with significant morbidity and mortality. Existing treatments including surgery, chemotherapy and radiation have poor overall survival rates and prognosis. The intended therapeutic effects of chemotherapy are limited by drug resistance, systemic toxicity and adverse effects. This review explores advances in OSCC treatment, with a focus on lipid-based platforms (solid lipid nanoparticles, nanostructured lipid carriers, lipid-polymer hybrids, cubosomes), polymeric nanoparticles, self-assembling nucleoside nanoparticles, dendrimers, magnetic nanovectors, graphene oxide nanostructures, stimuli-responsive nanoparticles, gene therapy, folic acid receptor targeting, gastrin-releasing peptide receptor targeting, fibroblast activation protein targeting, urokinase-type plasminogen activator receptor targeting, biotin receptor targeting and transferrin receptor targeting. This review also highlights oncolytic viruses as OSCC therapy candidates.

Mechanisms Behind the Pharmacological Application of Biochanin-A: A review.

This review was aimed at summarizing the cellular and molecular mechanisms behind the various pharmacological actions of biochanin-A. Many studies have been reported claiming its application in cancers, metabolic disorders, airway hyperresponsiveness, cardiac disorders, neurological disorders, etc. With regard to hormone-dependent cancers like breast, prostate, and other malignancies like pancreatic, colon, lung, osteosarcoma, glioma that has limited treatment options, biochanin-A revealed agreeable results in arresting cancer development. Biochanin-A has also shown therapeutic benefits when administered for neurological disorders, diabetes, hyperlipidaemia, and other chronic diseases/disorders. Isoflavones are considered phenomenal due to their high efficiency in modifying the physiological functions of the human body. Biochanin-A is one among the prominent isoflavones found in soy (glycine max), red clover (Trifolium pratense), and alfalfa sprouts, etc., with proven potency in modulating vital cellular mechanisms in various diseases. It has been popular for ages among menopausal women in controlling symptoms. In view of the multi-targeted functions of biochanin-A, it is essential to summarize it's mechanism of action in various disorders. The safety and efficacy of biochanin-A needs to be established in clinical trials involving human subjects. Biochanin-A might be able to modify various systems of the human body like the cardiovascular system, CNS, respiratory system, etc. It has shown a remarkable effect on hormonal cancers and other cancers. Many types of research on biochanin-A, particularly in breast, lung, colon, prostate, and pancreatic cancers, have shown a positive impact. Through modulating oxidative stress, SIRT-1 expression, PPAR gamma receptors, and other multiple mechanisms biochanin-A produces anti-diabetic action. The diverse molecular mechanistic pathways involved in the pharmacological ability of biochanin-A indicate that it is a very promising molecule and can play a major impact in modifying several physiological functions.

Notch signaling: A possible therapeutic target and its role in diabetic foot ulcers.

BACKGROUND & AIM: Diabetic foot ulcers are major cause of lower limb amputations in the diabetic population. The major factors that play a role in causing the delay of the process of healing in diabetic foot ulcers broadly are decreased angiogenesis, reduced proliferation and migration of keratinocytes/fibroblasts. The typical wound healing process has four phases which are overlapping with each other thus making the healing even more complex. Hence it is essential to identify a therapeutic target that involves the regulation of the cellular factors involved in healing and helps to increase angiogenesis and can regulate all four phases accordingly. METHOD: Literature review involved a search of the databases namely, PubMed, Cochrane, EMBASE, and Web of Science database. Articles were identified and retrieved that specifically dealt with Notch as a target in healing of wounds and its mechanism of action on various cells and phases of healing. RESULTS: Notch is a cell surface receptor which interacts with transmembrane ligands of the nearby cells and is involved in cell proliferation, differentiation, cell fate and death. It is also involved in cell-to-cell communication, cell signaling, and various phases of development. There exist four known notch genes and five ligands which interact with notch proteins. Hyperglycemia plays a role in the activation of the notch receptor thus causing the release of inflammatory mediators via macrophages. As notch can regulate macrophage-mediated inflammation it can serve as a therapeutic target for diabetic foot ulcers. CONCLUSION: This review focuses on the effect of notch on various cell mediators and phases of diabetic wound healing and deals with how notch activation or inhibition can serve as a potential therapeutic target for healing diabetic foot ulcers.

Sirtuins as therapeutic targets for improving delayed wound healing in diabetes.

Sirtuins are a vast family of histone deacetylases, which are NAD+ dependent enzymes, consisting of seven members, namely SIRT 1, SIRT 6 and SIRT 7 located within the nucleus, SIRT 2 in the cytoplasm and SIRT 3, SIRT 4 and SIRT 5 in the mitochondria. They have vital roles in regulating various biological functions such as age-related metabolic disorders, inflammation, stress response, cardiovascular and neuronal functions. Delayed wound healing is one of the complication of diabetes, which can lead to lower limb amputation if not treated timely. SIRT 1, 3 and 6 are potent targets for diabetic wound healing. SIRT 1 deficiency reduces recruitment of fibroblasts, macrophages, mast cells, neutrophils to wound site and delays wound healing; negatively expressing MMP-9. The SIRT 1 mediated signalling pathway in diabetic wound healing is the SIRT 1-FOXO-c-Myc pathway. On the contrary, SIRT 3 deficiency impairs proliferation and migration of fibroblasts and SIRT 6 deficiency impairs wound closure rate and interrupts the vascular remodelling. This review focuses on the role of sirtuins in improving delayed wound healing in diabetes and its natural modulators with their specific functions towards healing diabetic wounds.

Effect of dehydrozingerone, a half analog of curcumin on dexamethasone-delayed wound healing in albino rats.

Oxidative stress is triggered by the wound which results in the production of reactive oxygen species (ROS), thereby delaying normal wound repair. Therefore, it is important to reduce the level of ROS to improve healing. A known antioxidant, dehydrozingerone (DHZ) was synthesized and selected for the study. The authors aimed to investigate the wound healing action of topical (100 mg/wound) and systemic (100 mg/kg, p. o.). DHZ on different wound models in normal and dexamethasone (DEX)-suppressed healing. Topical DHZ showed a significant (P < 0.05) rise in tensile strength when compared to control in normal healing. Significant (P < 0.05) wound closure was observed from 3 to 9 days in DHZ oral and gel treated groups. There was a significant (P < 0.05) rise in hydroxyproline content with the DHZ treated groups when compared to control. Systemic DHZ exhibited a significant (P < 0.05) increase in lysyl oxidase (LO) levels of 3.73 ± 0.15 nmol of H(2)O(2) when compared to control. In DEX-suppressed healing, showed good pro-healing activity with respect to the parameters mentioned above. DHZ treatment exhibited a parabolic dose response of ROS inhibition with a plateau effect at 75 µM. There was a steady and constant increase in the % NO inhibition with increasing doses of DHZ. Oral DHZ is effective in accelerating the healing process in both normal and dexamethasone-suppressed wounds. Our study suggests that DHZ (half analog of curcumin) supplementation reduces the steroid-induced delay in wound healing.

Role of Statins in New-onset Diabetes Mellitus: The Underlying Cause, Mechanisms Involved, and Strategies to Combat.

Statins have transformed the treatment of cardiovascular diseases through primary and secondary prevention of events. Despite the success of statin's management of cardiovascular conditions, certain clinical trials, reviews, and meta-analysis point out that statins have the propensity to induce diabetes. The risk further increases with intensive statin therapy or in patients with diabetes. A proper mechanism for the induction of the diabetic condition has not yet been determined. The involvement of statin with beta cells in insulin secretion and peripheral cells in insulin resistance has been widely studied and established. The present review provides an update on the recent understanding of statin-induced diabetes. This covers the origin of statins, their development, possible mechanisms that explain the adverse effects in glucose homeostasis, and probable targets to remedy the condition.

In silico Study to Evaluate the Antiviral Activity of Novel Structures against 3C-like Protease of Novel Coronavirus (COVID-19) and SARS-CoV.

BACKGROUND: Globally, over 4.3 million laboratory confirmed cases of COVID-19 have been reported from over 105 countries. No FDA approved antiviral is available for the treatment of this infection. Zhavoronkov et al., with their generative chemistry pipeline, have generated structures that can be potential novel drug-like inhibitors for COVID-19, provided they are validated. 3C-like protease (3CLP) is a homodimeric cysteine protease that is present in coronaviruses. Interestingly, 3CLP is 96.1% structurally similar between SARS-CoV and SARS-CoV-2. OBJECTIVE: To evaluate interaction of generated structures with 3CLP of SARS-CoV (RCSB PDB ID: 4MDS). METHODS: Crystal structure of human SARS-CoV with a non-covalent inhibitor with resolution: 1.598 Å was obtained and molecular docking was performed to evaluate the interaction with generated structures. The MM-GBSA and IFD-SP were performed to narrow down to the structures with better binding energy and IFD score. The ADME analysis was performed on top 5 hits and further MD simulation was employed for top 2 hits. RESULTS: In XP docking, IFD-SP and molecular dynamic simulation studies, the top 2 hits 32 and 61 showed interaction with key amino acid residue GLU166. Structure 61, also showed interaction with HIS164. These interactions of generated structure 32 and 61, with GLU166 and HIS164, indicate the binding of the selected drug within the close proximity of 3CLP. In the MD simulation, the protein- ligand complex of 4MDS and structure 61 was found to be more stable for 10ns. CONCLUSION: These identified structures can be further assessed for their antiviral activity to combat SARS-CoV and COVID-19.

An Appraisal of Current Pharmacological Perspectives of Sesamol: A Review.

Sesame (Sesamum indicum L.) seeds have been authenticated for its medicinal value in both Chinese and Indian systems of medicine. Its numerous potential nutritional benefits are attributed to its main bioactive constituents, sesamol. As a result of those studies, several molecular mechanisms are emerging describing the pleiotropic biological effects of sesamol. This review summarized the most interesting in vitro and in vivo studies on the biological effects of sesamol. The present work summarises data available from Pubmed and Scopus database. Several molecular mechanisms have been elucidated describing the pleiotropic biological effects of sesamol. Its major therapeutic effects have been elicited in managing oxidative and inflammatory conditions, metabolic syndrome and mood disorders. Further, compelling evidence reflected the ability of sesamol in inhibiting proliferation of the inflammatory cell, prevention of invasion and angiogenesis via affecting multiple molecular targets and downstream mechanisms. Sesamol is a safe, non-toxic chemical that mediates anti-inflammatory effects by down-regulating the transcription of inflammatory markers such as cytokines, redox status, protein kinases, and enzymes that promote inflammation. In addition, sesamol also induces apoptosis in cancer cells via mitochondrial and receptor-mediated pathways, as well as activation of caspase cascades. In the present review, several pharmacological effects of sesamol are summarised namely, antioxidant, anti-cancer, neuroprotective, cardioprotective, anti-inflammatory, hypolipidemic, radioprotective, anti-aging, anti-ulcer, anti-dementia, anti-depressant, antiplatelet, anticonvulsant, anti-anxiolytic, wound healing, cosmetic (skin whitening), anti-microbial, matrix metalloproteinase (MMPs) inhibition, hepatoprotective activity and other biological effects. Here we have summarized the proposed mechanism behind these pharmacological effects.

Evaluation of the healing potential of Schrebera swietenioides in the dexamethasone-suppressed wound healing in rodents.

The wound healing potential of the aqueous, alcoholic extracts, and the butanolic fraction of the alcoholic extract obtained from the bark of Schrebera swietenioides were evaluated in the dexamethasone suppressed wound healing model. The work was conducted on rodents using incision, excision, and dead space wound models. The extracts of S swietenioides enhanced the breaking strength of incision wounds significantly (P < .05). Faster epithelization and contraction of excision wounds were observed in the treated groups (P < .05). Dead space wound model demonstrated an increase in breaking strength of granulation tissue and weight of dried granulation tissue after treatment with the extracts.The extracts attenuated the effect of dexamethasone on healing.The total RNA isolated from the granulation tissues of the extract-treated animals was significantly higher than in both dexamethasone and normal groups, (P < 0.05). It was observed that the DNA was intact in all the groups. These findings suggest that dexamethasone suppresses wound healing, possibly through an inappropriate transcription rather than causing DNA damage.The S swietenioides extracts have the capacity to reverse this effect.

Improved in vitro and in vivo hepatoprotective effects of liposomal silymarin in alcohol-induced hepatotoxicity in Wistar rats.

BACKGROUND: Silymarin, a known hepatoprotectant, owing to its poor oral bioavailability, has limited pharmacological effects. The present study was designed to improve its in vitro and in vivo hepatoprotection and increase its oral bioavailability against alcohol intoxication by formulating it in four different liposomal formulations namely conventional, dicetyl phosphate, stearyl amine and PEGylated liposomes. METHOD: The liposomes were prepared using phosphatidylcholine, cholesterol, and silymarin in addition to dicetyl phosphate, stearyl amine and DSPE mPEG 2000 by film hydration method with 5% sucrose as a cryo-protectant. The optimized formulations were studied for their release profile at pH 1.2 and 6.8. Liposomes were studied for in vitro protection on Chang liver cells and efficacious liposomes were selected for in vivo hepatoprotection study. Further, conventional liposomes were studied for bioavailability in alcohol intoxicated Wistar rats. RESULTS: The conventional liposomes increased in vitro release profile at pH 1.2 and 6.8 and also showed better in vitro protection compared to silymarin alone. Conventional and PEGylated liposomes showed better improvement in liver function, better efficacy in combating inflammatory conditions, better improvement in antioxidant levels and reversal of histological changes compared to silymarin alone. Conventional also showed an almost fourfold increase in area under the curve compared to silymarin suspension. CONCLUSION: Conventional and PEGylated liposomes of silymarin were found to be more efficacious as hepatoprotective against alcohol-induced hepatotoxicity by its free radical scavenging and anti-inflammatory effects. Conventional liposomes showed enhanced bioavailability compared to silymarin alone.

Epigenetic modulation of macrophage polarization- perspectives in diabetic wounds.

Diabetes is a chronic metabolic disorder that poses a global burden to healthcare. Increasing incidence of diabetes-related complications in the affected population includes a delay in wound healing that often results in non-traumatic limb amputations. Owing to the intricacies of the healing process and crosstalk between the multitude of participating cells, the identification of hyperglycaemia-induced changes at both cellular and molecular levels poses a challenge. Macrophages are one of the key participants in wound healing and continue to exert functional changes at the wound site since the time of injury. In the present review, we discuss the role of these cells and their aberrant functions in diabetic wounds. We have extensively studied the process of macrophage polarization (MP) and its modulation through epigenetic modifications. Data from both pre-clinical and clinical studies on diabetes have co-related hyperglycaemia induced changes in gene expression to an increased incidence of diabetic complications. Hyperglycaemia and oxidative stress, create an environment prone to changes in the epigenetic code, that is manifested as an altered inflammatory gene expression. Here, we have attempted to understand the different epigenetic modulations that possibly contribute towards dysregulated MP, resulting in delayed wound healing.

An Appraisal of Pumpkin Seed Extract in 1, 2-Dimethylhydrazine Induced Colon Cancer in Wistar Rats.

BACKGROUND: Cancer is one of the most important public health burdens in developed and developing countries. Colon cancer (CC) is the sixth most common cause of death in India and third most important cause in developed countries. For treating cancer, several synthetic agents are available but they cause side effects. Therefore, there is a need to investigate plant derived anticancer agents with lesser side effects. In this direction, we have made an attempt to unravel the potential of pumpkin seed extract for treating colon cancer. OBJECTIVE: The objective of this study was to evaluate pumpkin seed extract as prophylactic and treatment for 1, 2-dimethylhydrazine (DMH) induced colon cancer in Wistar rats. MATERIALS AND METHODS: Male Wistar rats were divided into seven groups, namely, control, DMH (disease control), 5-Flurouracil (standard), treatment groups (100mg/kg and 200 mg/kg), and pretreatment groups (100mg/kg and 200 mg/kg) with pumpkin seed extract. The animals were euthanised at the end of study and colons were examined. RESULTS: A significant difference in the aberrant crypt foci (ACF) number in all treatment groups compared to control and DMH groups were noted. Pretreatment group at a dose of 200 mg/kg showed a significant decrease in the colon length/weight ratio. Pretreatment groups showed a significant change in the colonic glutathione (GSH) and superoxide dismutase (SOD) levels when compared to control and DMH control. The nitrite content was decreased in treatment group 200 mg/kg at 5.203±0.852 when compared to DMH control at 8.506±3.866. All treatment groups demonstrated decreased hyperplasia and ACF in histology. CONCLUSION: Pumpkin seed may prevent the risk of CC when consumed in dietary proportions.

Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium: Development and in vitro and in vivo evaluations.

The aim of this study was to improve the pharmacokinetics and pharmacodynamics profile of rosuvastatin calcium by formulating long-circulating PEGylated chitosan nanoparticles (NPs). Chitosan was PEGylated by a carbodiimide mediated reaction, using a carboxylic acid derivative of PEG (polyethylene glycol). The NPs were optimised for particle size, polydispersity index, zeta potential and drug entrapment efficiency. In vitro drug release, pharmacokinetic and pharmacodynamics studies of the optimized nanoparticles were performed. PEGylation of chitosan was confirmed by FTIR analysis. Drug-excipient compatibility was studied by differential scanning calorimetry and FTIR analyses. Two batches of nanoparticles were optimized with particle size of <200nm and entrapment efficiency of ≈14%. In vitro drug release studies revealed cumulative release of 14.07±0.57% and 22.02±0.81% of rosuvastatin over the period of 120h, indicating appreciable sustained release of drug. TEM analysis showed the spherical structure of nanoparticles. Pharmacokinetic studies indicated that optimized NPs showed prolonged drug release over a period of 72h. Pharmacodynamics studies in hyperlipidemic rat model demonstrated greater lipid-lowering capability of rosuvastatin nanoparticles in comparison with plain rosuvastatin. The nanoparticles demonstrated substantial prolonged delivery of the drug in vivo along with better therapeutic action, which could be potential drug delivery modality for 'statins'.