Clinical Progress of Targeted Therapy for Breast Cancer: A Comprehensive Review.

The discovery of effective breast cancer therapy is both urgent and daunting, beset by a myriad of challenges that range from the disease's inherent heterogeneity to its complex molecular underpinnings. Drug resistance, the intricacies of the tumor microenvironment, and patient-specific variables further complicate this landscape. The stakes are even higher when dealing with subtypes like triple-negative breast cancer, which eludes targeted hormonal therapies due to its lack of estrogen, progesterone, and HER2 receptors. Strategies to overcome such challenges include combinations of drugs and identifying new drug targets. Developing new drugs based on such targets could be a better solution than relying on costly immunotherapy or combinational therapies. In this review, we have endeavored to comprehensively examine the proven therapeutic drug targets associated with breast cancer and elucidate their respective molecular mechanisms and current clinical status. This study aims to facilitate researchers in conducting a comparative analysis of different targets to select single and multi- targeted drug discovery approaches for breast cancer.

Alleviating Neurodegenerative Diseases Associated with Mitochondrial Defects by Therapeutic Biomolecules.

Neurodegenerative diseases are emerging as a global health concern in the current sce-nario, and their association with mitochondrial defects has been a potential area of research. Mi-tochondria, one of the essential organelles of the cell, serve as the cell's powerhouse, producing energy and ensuring cellular health. Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, amyotrophic lateral sclerosis, and Pelizaeus-Merzbacher disease have been found to be primarily triggered by mitochondrial malfunction. One of the key byproducts of mitochondrial respiration, reactive oxygen species, also contributes significantly to mitochondrial DNA muta-tions that eventually cause mitochondrial breakdown. This review paper comprehensively examines the potential of therapeutic biomolecules, specifi-cally mitochondria-specific antioxidants, in mitigating the impact of mitochondrial defects on neurodegenerative diseases. It provides a detailed analysis of the mechanisms involved in mito-chondrial dysfunction, the potential therapeutic targets of these biomolecules, and their structure-activity relationship information are also discussed in this review. Various research articles and publications were used extensively in compiling the data, and the structures of biomolecules were prepared using software such as ChemDraw and ChemSketch. Crucial elements triggering mitochondrial abnormalities were identified and a tabular compilation of bioactive antioxidant compounds along with their therapeutic targets, was presented. Mitochondria-specific antioxidant therapy is an innovative and promising strategy for the man-agement of neurodegenerative diseases associated with mitochondrial defects. This review pro-vides a thorough summary of the current state of research and promising avenues of research and development in this field, emphasizing the importance of further investigations and clinical trials to elucidate their therapeutic benefits.

Synthesis, in silico screening, and biological evaluation of novel pyridine congeners as anti-epileptic agents targeting AMPA (α-amino-3-hydroxy-5-methylisoxazole) receptors.

The research involves the synthesis of a series of new pyridine analogs 5(i-x) and their evaluation for anti-epileptic potential using in silico and in vivo models. Synthesis of the compounds was accomplished by using the Vilsmeier-Haack reaction principle. AutoDock 4.2 was used for their in silico screening against AMPA (-amino-3-hydroxy-5-methylisoxazole) receptor (PDB ID:3m3f). For in vivo testing, the maximal electroshock seizure (MES) model was used. The physicochemical, pharmacokinetic, drug-like, and drug-score features of all synthesized compounds were assessed using the online Swiss ADME and Protein Plus software. The in silico results showed that all the synthesized compounds 5(i-x) had 1-3 interactions and affinities ranging from -6.5 to -8.0 kJ/mol with the targeted receptor compared to the binding affinities of the standard drug phenytoin and the original ligand of the target (P99), which were -7.6 and -6.8 kJ/mol, respectively. In vivo study results showed that the compound 5-Carbamoyl-2-formyl-1-[2-(4-nitrophenyl)-2-oxo-ethyl]-pyridinium gave 60% protection against epileptic seizures compared to 59% protection afforded by regular phenytoin. All of them met Lipinski's rule of five and had drug-likeness and drug score values of 0.55 and 0.8, respectively, making them chemically and functionally like phenytoin. According to the findings of the studies, the synthesized derivatives have the potential to be employed as a stepping stone in the development of novel anti-epileptic drugs.

Recent Insight into Herbal Bioactives-Based Novel Approaches for Chronic Intestinal Inflammatory Disorders Therapy.

Inflammatory bowel disease (IBD) is a life-threatening complex disease. It causes chronic intestinal inflammation in GIT. IBD significantly affects people's lifestyles and carries a high risk of colon cancer. IBD involves the rectum, ileum, and colon, with clinical manifestations of bloody stools, weight loss, diarrhea, and abdominal pain. The prevalence of inflammatory disease is increasing dramatically worldwide. Over 16 million people are affected annually in India, with an economic burden of $6.8- $8.8 billion for treatment. Modern medicine can manage IBD as immunosuppressive agents, corticosteroids, tumor necrosis factor antagonists, integrin blockers, and amino-salicylates. However, these approaches are allied with limitations such as limited efficacy, drug resistance, undesired side effects, and overall cost, which cannot be ignored. Hence, the herbal bioactives derived from various plant resources can be employed in managing IBD. Science Direct, PubMed, Google, and Scopus databases have been searched for conclusively relevant herbal plant-based anti-inflammatory agent compositions. Studies were screened through analysis of previously published review articles. Eminent herbal bioactives, namely curcumin, resveratrol, ellagic acid, silybin, catechin, kaempferol, icariin, glycyrrhizin acid, berberine, quercetin, rutin, and thymol are reported to be effective against IBD. Herbal leads are promising treatment options for IBD; they have been shown to display antiinflammatory and antioxidant properties by targeting enzymes and regulating the expressions of various inflammatory mediators. Natural products have been reported to have anti-inflammatory properties in various clinical and preclinical studies, and some are available as herbal preparations. Herbal medicine would be promising in association with the implication of a novel drug delivery system for managing IBD.

In Search of Novel SGLT2 Inhibitors by High-throughput Virtual Screening.

BACKGROUND: Type 2 diabetes mellitus constitutes approximately 90% of all reported forms of diabetes mellitus. Insulin resistance characterizes this manifestation of diabetes. The prevalence of this condition is commonly observed in patients aged 45 and above; however, there is an emerging pattern of younger cohorts receiving diagnoses primarily attributed to lifestyle-related variables, including obesity, sedentary behavior, and poor dietary choices. The enzyme SGLT2 exerts a negative regulatory effect on insulin signaling pathways, resulting in the development of insulin resistance and subsequent elevation of blood glucose levels. The maintenance of glucose homeostasis relies on the proper functioning of insulin signaling pathways, while disruptions in insulin signaling can contribute to the development of type 2 diabetes. OBJECTIVE: Our study aimed to investigate the role of SGLT2. This enzyme interferes with insulin signaling pathways and identifies potential SGLT2 inhibitors as a treatment for managing type 2 diabetes. METHODS: We screened the Maybridge HitDiscover database to identify potent hits followed by druglikeness, Synthetic Accessibility, PAINS alert, toxicity estimation, ADME assessment, and Consensus Molecular docking. RESULTS: The screening process led to the identification of three molecules that demonstrated significant binding affinity, favorable drug-like properties, effective ADME, and minimal toxicity. CONCLUSION: The identified molecules could manage T2DM effectively by inhibiting SGLT2, providing a promising avenue for future therapeutic strategies.

Novel Approaches for the Management of Type 2 Diabetes Mellitus: An Update.

Diabetes mellitus is an irreversible, chronic metabolic disorder indicated by hyperglycemia. It is now considered a worldwide pandemic. T2DM, a spectrum of diseases initially caused by tissue insulin resistance and slowly developing to a state characterized by absolute loss of secretory action of the ß cells of the pancreas, is thought to be caused by reduced insulin secretion, resistance to tissue activities of insulin, or a combination of both. Insulin secretagogues, biguanides, insulin sensitizers, alpha-glucosidase inhibitors, incretin mimetics, amylin antagonists, and sodium-glucose co-transporter-2 (SGLT2) inhibitors are the main medications used to treat T2DM. Several of these medication's traditional dosage forms have some disadvantages, including frequent dosing, a brief half-life, and limited absorption. Hence, attempts have been made to develop new drug delivery systems for oral antidiabetics to ameliorate the difficulties associated with conventional dosage forms. In comparison to traditional treatments, this review examines the utilization of various innovative therapies (such as microparticles, nanoparticles, liposomes, niosomes, phytosomes, and transdermal drug delivery systems) to improve the distribution of various oral hypoglycemic medications. In this review, we have also discussed some new promising candidates that have been approved recently by the US Food and Drug Administration for the treatment of T2DM, like semaglutide, tirzepatide, and ertugliflozin. They are used as a single therapy and also as combination therapy with drugs like metformin and sitagliptin.

Current Market Potential and Prospects of Copper-based Pyridine Derivatives: A Review.

Nicotine, minodronic acid, nicotinamide (niacin), zolpidem, zolimidine, and other pyridine-based chemicals play vital roles in medicine and biology. Pyridine-containing drugs are widely available on the market to treat a wide range of human ailments. As a result of these advances, pyridine research is continually expanding, and there are now higher expectations for how it may aid in the treatment of numerous ailments. This evaluation incorporates data acquired from sources, like PubMed, to provide a thorough summary of the approved drugs and bioactivity data for compounds containing pyridine. Most of the reactions discussed in this article will provide readers with a deeper understanding of various pyridine-related examples, which is necessary for the creation of copper catalysis-based synthetic processes that are more accessible, secure, environmentally friendly, and practical, and that also have higher accuracy and selectivity. This paper also discusses significant innovations in the multi-component copper-catalyzed synthesis of N-heterocycles (pyridine), with the aim of developing precise, cost-effective, and environmentally friendly oxygenation and oxidation synthetic methods for the future synthesis of additional novel pyridine base analogs. Therefore, the review article will serve as a novel platform for researchers investigating copper-based pyridine compounds.

Recent updates on transdermal drug delivery approaches for the management of gout and its clinical perspective.

Oral and injectable drug administration have recently been replaced with transdermal drug delivery (TDD) approaches, which are less intrusive, less likely to be rejected by patients, and easier to administer. There is still room for improvement in the treatment of gout with the use of a TDD system. Gout has become a worldwide epidemic and a severe threat to human beings. Gout treatment can be accomplished in various ways, including orally and intravenously. Several traditional options are still useless, cumbersome, and potentially dangerous. Hence, gout therapeutic options are desperately required for more effective and less toxic drug delivery methods. Anti-gout medications using TDD could substantially influence obese people in the future, even if most trials are still in the animal stages. Thus, this review aimed to provide a concise overview of recent TDD technologies and anti-gout medication delivery methods that improved therapeutic efficacy and bioavailability. Moreover, clinical updates on investigational drugs have been discussed to address the potential findings against gout.

Review deciphering potent therapeutic approaches targeting Notch signaling pathway in breast cancer.

In the current period of drug development, natural products have provided an unrivaled supply of anticancer medications. By modifying the cancer microenvironment and various signaling pathways, natural products and their derivatives and analogs play a significant role in cancer treatment. These substances are effective against several signaling pathways, particularly the cell death pathways (apoptosis and autophagy) and embryonic developmental pathways (Notch, Wnt, and Hedgehog pathways). Natural products have a long history, but more research is needed to understand their current function in the research and development of cancer treatments and the potential for natural products to serve as a significant source of therapeutic agents in the future. Several target-specific anticancer medications failed to treat cancer, necessitating research into natural compounds with multiple target properties. To help develop a better treatment plan for managing breast cancer, this review has outlined the anticancerous potential of several therapeutic approaches targeting the notch signaling system in breast tumors.

Cancer Proteomics for Cellular Dysfunction: Insights and Trends.

BACKGROUND: Cancer is an ailment with having a very low survival rate globally. Poor cancer prognosis is primarily caused by the fact that people are found to have the disease when it is already well advanced. The goal of this study is to compile information on new avenues of investigation into biomarkers that may facilitate the routine detection of cancer. Proteomic analysis has recently developed into a crucial technique for cancer biology research, working in tandem with genomic analysis. Mass spectrometry techniques are one of several proteome analysis techniques that allow for the highly precise quantitative and qualitative recognition of hundreds of proteins in small quantities from various biological materials. These findings might soon serve as the foundation for better cancer diagnostic techniques. METHODS: An exhaustive literature survey has been conducted using electronic databases such as Google Scholar, Science Direct, and PubMed with keywords of proteomics, applications of proteomics, the technology of proteomics, biomarkers, and patents related to biomarkers. RESULT: Studies reported till 2021 focusing on cancer proteomics and the related patents have been included in the present review to obtain concrete findings, highlighting the applications of proteomics in cancer. CONCLUSION: The present review aims to present the overview and insights into cancer proteomics, recent breakthroughs in proteomics techniques, and applications of proteomics with technological advancements, ranging from searching biomarkers to the characterization of molecular pathways, though the entire process is still in its infancy.

An Insight into the Hepatoprotective Activity and Structure-activity Relationships of Flavonoids.

BACKGROUND: Flavonoids are a class of polyphenolic bioactive compounds obtained from plants, which have a wide range of chemical structures and properties. More than 9000 distinct flavonoid molecules have been identified and have been found to regulate numerous developmental processes and play key biological roles in living organisms. OBJECTIVE: This review aims to highlight the hepatoprotective potentiality of flavonoids and corelate their pharmacological activity with their chemical structure. METHODS: With the advancement in the field of research related to phytochemicals, it is evident that flavonoids have versatile health benefits, viz., antioxidant property, free radical scavenging capacity, anticancer activity. The basic structures are C6-C3-C6 rings with various substitution patterns, resulting in a succession of subclass compounds, and the relationships between chemical structures and bioactivity have previously been investigated. RESULTS: The hepatoprotective effects of bioactive flavonoids derived from plants have been widely linked to their antioxidant activity, antiinflammatory activity, effects on Sterol Regulatory Element- binding Proteins (SREBP), Peroxisome Proliferator-activated Receptor gamma (PPARγ) receptors, and inflammatory mediator cytokines according to numerous studies. The C2-C3 double bond at the A ring, as well as the hydroxyl groups of C3'or C4', and the carbonyl group at position C4, have been shown to augment their hepatoprotective activities; however, hydroxymethylation at C3' and C4' has been found to diminish the hepatoprotective activity. CONCLUSION: The impact of flavonoid moieties and the structure-activity relationship of flavonoids related to combating various hepatic disorders have been vividly discussed in this review paper.

Exploring Synthesis and Chemotherapeutic Potential of Thiosemicarbazide Analogs.

BACKGROUND: Cancer is a leading cause of death worldwide, accounting for nearly 10 million deaths in 2020. Researchers are continually finding new and more effective medications to battle the diseases. OBJECTIVE: The objective of this study is to identify the emerging role of Thiosemicarbazide analogs for different types of cancer targets with a glance at different novel synthetic routes reported for their synthesis. METHODS: A systematic literature review was conducted from various sources over the last 15 years with the inclusion of published research and review articles that involves the synthesis and use of thiosemicarbazide analogs for different targets of cancer. Data from the literature review for synthesis and anticancer potential for specific targets for cancer studies of thiosemicarbazide analogs are summarized in the paper. RESULTS: There are several emerging studies for new synthetic routes of thiosemicarbazide derivatives with their role in various types of cancers. The main limitation is the lack of clinical trial of the key findings for the emergence of new anticancer medication with thiosemicarbazide moiety. CONCLUSION: Emerging therapies exist for use of a limited number of medications for the treatment of cancer; results of the ongoing studies will provide more robust evidence in the future.

Insight into the Various Approaches for the Enhancement of Bioavailability and Pharmacological Potency of Terpenoids: A Review.

Terpenoids are naturally occurring secondary metabolites that consist of isoprene units (i.e., 2-methyl-1,3-butadiene). Terpenoids became recognized because of their diverse pharmacological benefits, such as anti-cancer, anti-inflammatory, antioxidant, analgesic, antibacterial, antifungal, hepatoprotective, antiviral, and antiparasitic activities. But most of these compounds have limited lipophilicity, dissolution rate, aqueous solubility, and drug permeability, so they are not used effectively. The low bioavailability significantly interferes with the performance of terpenoids to cure diseases, and the absorption process of terpenoids also becomes disrupted; therefore, their bioavailability in the blood becomes insufficient to achieve optimal treatment activity. Thus, to overcome this limitation, some strategies are used, such as nanotechnology (nanoparticles, carrier complexation), cocrystal, and glycosylation. Thus, this review summarizes the chemistry of terpenoids, factors that limit the bioavailability of terpenoids, and strategies employed to date with their design principles and outcomes possibly increasing their bioactivity.

An Insight into Diverse Activities and Targets of Flavonoids.

BACKGROUND: Flavonoids belong to the chemical class of polyphenols and are in the category of secondary metabolites imparting a wide protective effect against acute and chronic diseases. OBJECTIVE: The study aims to investigate and summarize the information of various flavonoids extracted, isolated from various sources, and possess different pharmacological properties by acting on multiple targets. METHODS: This comprehensive review summarizes the research information related to flavonoids and their pharmacological action targets from various sources like PubMed, Google Scholar and Google websites. RESULTS: Extracted information in the paper discusses various therapeutic effects of flavonoids isolated from medicinal plant sources, which have the property to inhibit several enzymes, which finally results in health benefits like anti-cancer, anti-bacterial, antioxidant, anti-allergic, and anti-viral effects. This study also showed the different solvents and methods involved in the extraction and characterization of the isolated phytochemical constituents. CONCLUSION: The findings showed the contribution of several flavonoids in the management and inhibition of various acute and chronic sicknesses by acting on different sites in the body. This study may lead to gaining interest for more research on the bioactives of different medicinal plants for the discovery of new lead compounds or further improvement of the efficacy of the existing compound.

Preformulation screening of lipids using solubility parameter concept in conjunction with experimental research to develop ceftriaxone loaded nanostructured lipid carriers

Abstract Development of ceftriaxone loaded nanostructured lipid carriers to increase permeability of ceftriaxone across uninflamed meninges after parenteral administration. Lipids were selected by theoretical and experimental techniques and optimization of NLCs done by response surface methodology using Box-Behnken design. The Δδt for glyceryl monostearate and Capryol90 were 4.39 and 2.92 respectively. The drug had maximum solubility of 0.175% (w/w) in glycerol monostearate and 2.56g of Capryol90 dissolved 10mg of drug. The binary mixture consisted of glyceryl monostearate and Capryol90 in a ratio of 70:30. The optimized NLCs particle size was 130.54nm, polydispersity index 0.28, % entrapment efficiency 44.32%, zeta potential -29.05mV, and % drug loading 8.10%. In vitro permeability of ceftriaxone loaded NLCs was 5.06x10-6 cm/s; evidently, the NLCs pervaded through uninflamed meninges, which, was further confirmed from in vivo biodistribution studies. The ratio of drug concentration between brain and plasma for ceftriaxone loaded NLCs was 0.29 and that for ceftriaxone solution was 0.02. With 44.32% entrapment of the drug in NLCs the biodistribution of ceftriaxone was enhanced 7.9 times compared with that of ceftriaxone solution. DSC and XRD studies revealed formation of imperfect crystalline NLCs. NLCs improved permeability of ceftriaxone through uninflamed meninges resulting in better management of CNS infections.

Potential of Nanotechnology-based Formulations in Combating Pulmonary Infectious Diseases: A Current Scenario.

BACKGROUND: Pulmonary microbial infection is mainly caused by microbes like atypical bacteria, viruses, and fungi, on both the upper and lower respiratory tracts. One of the demands of the present is the use of nanotechnology-based treatments to fight various lung infections. AIM: The main aim of the study is to explore all pulmonary infectious diseases and to compare the advanced and novel treatment approaches with the conventional methods which are available to treat infections. METHODS: This work sheds light on pulmonary infectious diseases with their conventional and present treatment approaches along with a focus on the advantageous roles of nano-based formulations. In the literature, it has been reported that the respiratory system is the key target of various infectious diseases which gives rise to various challenges in the treatment of pulmonary infections. RESULTS: The present review article describes the global situation of pulmonary infections and the different strategies which are available for their management, along with their limitations. The article also highlights the advantages and different examples of nanoformulations currently combating the limitations of conventional therapies. CONCLUSION: The content of the present article further reflects on the summary of recently published research and review works on pulmonary infections, conventional methods of treatment with their limitations, and the role of nano-based approaches to combat the existing infectious diseases which will jointly help the researchers to produce effective drug formulations with desired pharmacological activities.

Insights into Interactions of Human Cytochrome P450 17A1: A Review.

Cytochrome P450s are a widespread and vast superfamily of hemeprotein monooxygenases that metabolize physiologically essential chemicals necessary for most species' survival, ranging from protists to plants to humans. They catalyze the synthesis of steroid hormones, cholesterol, bile acids, and arachidonate metabolites and the degradation of endogenous compounds, such as steroids, fatty acids, and other catabolizing compounds as an energy source and detoxifying xenobiotics, such as drugs, procarcinogens, and carcinogens. The human CYP17A1 is one of the cytochrome P450 genes located at the 10q chromosome. The gene expression occurs in the adrenals and gonads, with minor amounts in the brain, placenta, and heart. This P450c17 cytochrome gene is a critical steroidogenesis regulator which performs two distinct activities: 17 alpha-hydroxylase activity (converting pregnenolone to 17- hydroxypregnenolone and progesterone to 17-hydroxyprogesterone; these precursors are further processed to provide glucocorticoids and sex hormones) and 17, 20-lyase activity (which converts 17-hydroxypregnenolone to DHEA). Dozens of mutations within CYP17A1 are found to cause 17-alpha-hydroxylase and 17, 20-lyase deficiency. This condition affects the function of certain hormone-producing glands, resulting in high blood pressure levels (hypertension), abnormal sexual development, and other deficiency diseases. This review highlights the changes in CYP17A1 associated with gene-gene interaction, drug-gene interaction, chemical-gene interaction, and its biochemical reactions; they have some insights to correlate with the fascinating functional characteristics of this human steroidogenic gene. The findings of our theoretical results will be helpful to further the design of specific inhibitors of CYP17A1.

In Vitro and In Vivo Approaches for Screening the Potential of Anticancer Agents: A Review.

BACKGROUND: Anticancer drug development is a tedious process, requiring several in vitro, in vivo, and clinical studies. In order to avoid chemical toxicity in animals during an experiment, it is necessary to envisage toxic doses of screened drugs in vivo at different concentrations. Several in vitro and in vivo studies have been reported to discover the management of cancer. MATERIALS AND METHODS: This study focused on bringing together a wide range of in vivo and in vitro assay methods developed to evaluate each hallmark feature of cancer. RESULT: This review provides detailed information on target-based and cell-based screening of new anticancer drugs in the molecular targeting period. This would help in inciting an alteration from the preclinical screening of pragmatic compound-orientated to target-orientated drug selection. CONCLUSION: Selection methodologies for finding anticancer activity have importance for tumor- specific agents. In this study, advanced rationalization of the cell-based assay is explored along with broad applications of the cell-based methodologies considering other opportunities.

Elucidation of S-Allylcysteine Role in Inducing Apoptosis by Inhibiting PD-L1 Expression in Human Lung Cancer Cells.

AIM: The aim of this study is to explore the therapeutic potential of S-allylcysteine (SAC) organosulphur compound as a potent immune checkpoint inhibitor PD-L1. BACKGROUND: Natural compounds have been showing tremendous anticancerous potential via suppressing the expression of genes involved in the development and progression of several carcinomas. This has further motivated us to explore the therapeutic potential of organosulphur compounds as potent immune checkpoint inhibitors. OBJECTIVE: Our study was designed to elucidate the potential of S-allylcysteine (SAC) as significant PD-L1 (immune checkpoint) inhibitor in human lung cancer A549 cancer cell line by using both the in vitro and in silico approaches. METHODS: Anticancerous effect of the SAC on lung cancer cells was determined by using the MTT cell viability. Apoptotic induction was confirmed by Hoechst staining, percent caspase-3 activity as well as gene expression analysis by real time PCR. Reactive Oxygen Species (ROS) was estimated by DCFDA method. Additionally, ligand-target protein interaction was analysed by molecular docking. RESULT: Cell growth and proliferation was significantly reduced in SAC treated A549 cells in a concentration and time.dependent manner. The effect of SAC on apoptotic induction was analyzed by enhanced nuclear condensation, increased percent caspase-3 activity as well as modulation of apoptotic genes. Furthermore, SAC treatment also resulted in reduced expression of PD-L1 and HIF-1α. Additionally, in silico analysis also supported the in vitro findings by showing efficient docking with PD-L1 immune checkpoint target. CONCLUSION: Therefore, our results clearly suggested that SAC could serve as a novel chemotherapeutic candidate for the treatment of lung cancer by inhibiting immune checkpoint target PD-L1 in human lung cancer cells. Additionally, our study also explained a novel molecular mechanism of its antitumor activity.

Optimization of polymeric nano drug delivery system using 3(2) full factorial design.

This study investigated the utility of a 3(2) factorial design and optimization process for nanoparticle suspension prepared by two different polymers Eudragit(®) RS 100 and Eudragit (®) RL 100 respectively. Total 18 formulations (9 formulations with each polymer) were prepared by solvent displacement technique. In these designs, two factors namely polymer weight (X1) and Aq. phase volume (X2) were evaluated each at three levels and experimental trials were performed at all nine possible combinations. Polymer weight (X1) and aqueous phase volume (X2) were selected as independent variables and particle size (Y1), % entrapment (Y2), drug release at 12(th) hrs. (Y3) are chosen as depended variables. In case of 3(2) factorial design, a full-model polynomial equation was established by subjecting the transformed values of independent variables to multiple regression analysis, and contour plots were drawn using the equation. The derived polynomial equations for particle size and % drug entrapment were verified by check point formulation. The result showed a wide variation in the responses for both of the polymer. For RS 100 polymer, particle size was 112-350 nm, entrapment: 26-72%, drug release was 42- 89% at 12(th) hrs. and for RL 100 polymer, particle size was 114-390 nm, entrapment: 30-72%, drug release was 50-90% at 12(th) hrs. The application of factorial design yielded a statistically systematic approach for the formulation and optimization of nanoparticles with desired particle size and high entrapment efficiency and release profile. The results of the optimized formulations showed particle size 225 nm, 63% drug entrapment and 83% drug release for RS 100 polymer and particle size was 148 nm, drug entrapment was 57%, drug release was 80% for RL 100 polymer.