Publications by authors named "Neelesh Kumar Mehra"

Article Synopsis
  • Researchers developed coamorphous systems (CAM) using lumefantrine (LMF) and alpha-ketoglutaric acid (KGA) to improve LMF's solubility and bioavailability through three distinct methods: liquid-assisted grinding, solvent evaporation, and quench-cooling.
  • Testing via PXRD, DSC, and other techniques confirmed the successful amorphization and intermolecular interactions in these CAMs, along with simulations showing diverse molecular environments.
  • The new CAMs significantly enhanced solubility (up to 14.73x), dissolution rates (up to 2.63x), and pharmacokinetics in living organisms (up to 10.86x), while also demonstrating anti-cancer
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To treat diabetic wound healing with a novel Thymoquinone (TQ) loaded nanoformulation by using combination of essentials oils. TQ nanoemulsion (NE) was developed with seabuckthorn & lavender essential oils by phase inversion method and mixture design. Further, DIAGEL is obtained by incorporating NE into 1% carbopol934.

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Osteoarthritis (OA) is a chronic joint disease that results in biomechanical and morphological changes that contribute to cartilage degradation. Ketoprofen (KP), used in the treatment of OA, is a selective inhibitor of cyclooxygenase-2 (COX-2). Topical administration of KP bypasses gastric irritation as well as first-pass metabolism and increases localized delivery.

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Article Synopsis
  • Ocular drug delivery faces challenges due to anatomical barriers, but ultradeformable vesicles like "transniosomes" may enhance corneal penetration and bioavailability.
  • The research developed brinzolamide-loaded transniosomes (BRZ-TN) that showed a vesicle size of 112.06 nm and a high entrapment efficiency of 93.63%.
  • Optimized BRZ-TN demonstrated better permeability and reduced intraocular pressure by 37% in pre-clinical tests, indicating its effectiveness as a superior nanocarrier for ocular treatments.
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The utilization of ionic liquids (ILs) in pharmaceutical drug delivery applications has seen significant expansion in recent years, owing to their distinctive characteristics and inherent adjustability. These innovative compounds can be used to tackle challenges associated with traditional dosage forms, such as polymorphism, inadequate solubility, permeability, and efficacy in topical drug delivery systems. Here, we provide a brief classification of ILs, and their effectiveness in augmenting transmucosal drug delivery approaches by improving the solubility and permeability of active pharmaceutical ingredients (APIs) by temporary mucus modulation aiding the paracellular transport of APIs, prolonging drug retention, and, thus, aiding controlled drug release across various mucosal surfaces.

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Aim: The aim of the present review is to shed light on the nanotechnological approaches adopted to overcome the shortcomings associated with the delivery of venom peptides which possess inherent anti-cancer properties.

Background: Venom peptides although have been reported to demonstrate anti-cancer effects, they suffer from several disadvantages such as in vivo instability, off-target adverse effects, limited drug loading and low bioavailability. This review presents a comprehensive compilation of different classes of nanocarriers while underscoring their advantages, disadvantages and potential to carry such peptide molecules for in vivo delivery.

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To investigate the pemetrexed encapsulated polymeric mixed micelles (PMMs) against breast cancer treatment. We meticulously optimized the formulation and conducted extensive characterizations, including photon correlation spectroscopy for micellization, advanced analytical techniques and cell line assessments. The PMM exhibited favorable characteristics, with a spherical morphology, hydrodynamic particle size of 19.

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Breast cancer continues to pose a substantial global health challenge, emphasizing the critical need for the advancement of novel therapeutic approaches. Key players in the regulation of apoptosis, a fundamental process in cell death, are the B-cell lymphoma 2 (Bcl-2) family proteins, namely Bcl-2 and Bax. These proteins have garnered attention as highly promising targets for the treatment of breast cancer.

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Various cancer models have been developed to aid the understanding of the underlying mechanisms of tumor development and evaluate the effectiveness of various anticancer drugs in preclinical studies. These models accurately reproduce the critical stages of tumor initiation and development to mimic the tumor microenvironment better. Using these models for target validation, tumor response evaluation, resistance modeling, and toxicity comprehension can significantly enhance the drug development process.

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This study aims to explore potential of transniosomes, a hybrid vesicular system, as ocular drug-delivery vehicle. Thin-film hydration technique was used to fabricate brinzolamide-loaded transniosomes (BRZ-TN) and optimized using Box-Behnken design, further exhaustively characterized for physicochemical evaluations, deformability, drug release, permeation and preclinical evaluations for antiglaucoma activity. The BRZ-TN showed ultradeformability (deformability index: 5.

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As a major public health issue, colorectal cancer causes 9.4% of total cancer-related deaths and comprises 10% of new cancer diagnoses worldwide. In the year 2023, an estimated 153,020 people are expected to receive an identification of colorectal cancer (CRC), resulting in roughly 52,550 fatalities anticipated as a result of this illness.

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Breast cancer (BC) is a heterogeneous disease with various morphological features, clinicopathological conditions and responses to different therapeutic options, which is responsible for high mortality and morbidity in women. The heterogeneity of BC necessitates new strategies for diagnosis and treatment, which is possible only by cautious harmonization of the advanced nanomaterials. Recent developments in vesicular nanocarrier therapy indicate a paradigm shift in breast cancer treatment by providing an integrated approach to address current issues.

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Cytochrome P450 1B1, a tumor-specific overexpressed enzyme, significantly impairs the pharmacokinetics of several commonly used anticancer drugs including docetaxel, paclitaxel and cisplatin, leading to the problem of resistance to these drugs. Currently, there is no CYP1B1 inhibition-based adjuvant therapy available to treat this resistance problem. Hence, in the current study, exhaustive studies including scaffold hopping followed by molecular docking, three-dimensional quantitative structure-activity relationships (3D-QSAR), molecular dynamics and free energy perturbation studies were carried out to identify potent and selective CYP1B1 inhibitors.

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Breast cancer (BC) remains a significant health burden worldwide, necessitating the development of innovative therapeutic strategies. The B-cell lymphoma 2 (Bcl-2) family proteins, Bcl-2 and Bax, play a crucial role in regulating apoptosis and thus are promising targets for BC therapy. We focus on the recent advancements in novel formulations that specifically target Bcl-2/Bax pathway to combat BC.

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The pharmaceutical industry is grappling with a pressing crisis in drug development characterized by soaring R&D costs, setbacks in blockbuster drug development due to poor aqueous solubility, and patent-related limitations on newly approved molecules. To combat these challenges, diverse strategies have emerged to enhance the solubility and dissolution rates of Biopharmaceutics Classification System (BCS) II and IV drug molecules. Enter drug nanocrystals, a revolutionary nanotechnology-driven, carrier-free colloidal drug delivery system.

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Study aimed to design and development of a supramolecular formulation of sulpiride (SUL) to enhance its solubility, dissolution and permeability by targeting a novel GlyT1 inhibition mechanism. SUL is commonly used to treat gastric and duodenal ulcers, migraine, anti-emetic, anti-depressive and anti-dyspeptic conditions. Additionally, Naringin (NARI) was incorporated as a co-former to enhance the drug's intestinal permeability by targeting P-glycoprotein (P-gp) efflux inhibition.

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The wound curation dressing material should own explicit elements to aggrandize wound cessation. The cryogel of poly(vinyl alcohol) (PVA) and hyaluronic acid (HA) is deemed to promote the angiogenesis, production of extracellular matrix components, granulation, and epithelialization. The research aims to tailor and evaluate the composite PVA/HA cryogel ingrained ferulic acid-loaded nanoemulsion patch labeled as PH-FemuFrost to improve the therapeutic properties and mechanical strength of the patches.

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Cyclodextrin complexes loaded with venetoclax for improved solubility and therapeutic efficacy as repurposed drug. The venetoclax-cyclodextrin inclusion complex was prepared using kneading method. Primarily in-silico molecular docking study was performed to examine the possible interaction between venetoclax and hydroxypropyl-β-cyclodextrin (HP-β-CD) and extensively characterized.

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Targeted drug delivery is an advanced approach for active targeting of tumor that can enhance the concentration of the drug at the site of action and reduce the off-target toxicity and non-specific effects of the drug. Folate receptors (FR) are membrane-bound surface proteins, over-expressed in numerous solid tumors, folate and folate conjugates bind to FR with higher affinity. In the present investigation, we fabricated Folic acid (FA) decorated Palbociclib loaded lipid-polymer hybrid nanoparticles (FA-PLPHNPs) using quality by design (QbD) approach and evaluated its anti-cancer activity in folate receptor-positive breast cancer cell lines.

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In today's culture, obesity and overweight are serious issues that have an impact on how quickly diabetes develops and how it causes complications. For the development of more effective therapies, it is crucial to understand the molecular mechanisms underlying the chronic problems of diabetes. The most prominent effects of diabetes are microvascular abnormalities such as retinopathy, nephropathy, and neuropathy, especially diabetes foot ulcers, as well as macrovascular abnormalities such as heart disease and atherosclerosis.

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The current research involved the development and validation of an easy, cost-effective, and sensitive bioanalytical reverse-phase high-performance liquid chromatography method for the assessment of palbociclib (PAL) in rat plasma and kidney, liver, spleen and heart. A response surface methodology-based Box-Behnken design was used to optimize critical chromatographic conditions such as buffer pH, organic phase concentration and flow rate to attain good sensitivity, tailing factor and retention time. The conditions were: pH of buffer, 4.

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Our main aim to design and develop a novel 4-carboxy phenyl boronic acid (4-CPBA) conjugated Palbociclib (PALB) loaded pH-sensitive chitosan lipid nanoparticles (PPCL) to enhance the anti-cancer efficacy of the PALB in in-vitro cell line studies by loading into 4-CPBA conjugated chitosan lipid nanoparticles. 4-CPBA was conjugated to chitosan by carbodiimide chemistry and formation of conjugate was confirmed by HNMR, ATR-FTIR spectroscopic techniques. Ionic-gelation method was used for the fabrication of PPCL and particles size, PDI, zeta potential were found to be 226.

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Even though chemotherapy stands as a standard option in the therapy of TNBC, problems associated with it such as anemia, bone marrow suppression, immune suppression, toxic effects on healthy cells, and multi-drug resistance (MDR) can compromise their effects. Nanoparticles gained paramount importance in overcoming the limitations of conventional chemotherapy. Among the various options, nanotechnology has appeared as a promising path in preclinical and clinical studies for early diagnosis of primary tumors and metastases and destroying tumor cells.

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One of the most prevalent cancers affecting women globally is cervical cancer. Cervical cancer is thought to cause 570 000 new cases annually, and standard treatments can have serious side effects. In this work, the main aim is to design, fabrication, and evaluation of carboplatin loaded chitosan coated liposomal formulation (CCLF-I) for vaginal delivery in the treatment of cervical cancer.

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Breast cancer is reported as one of the most prevalent non-cutaneous malignancies in women. Venetoclax (VEN) is an approved BCl-2 inhibitor for the treatment of chronic myeloid leukemia with very limited oral bioavailability and exhibits an enormous impact on breast cancer. In the current investigation, venetoclax-loaded self-nanoemulsifying drug delivery systems (VEN-SNEDDS) were designed and fabricated to improve the aqueous solubility, permeability, and anticancer efficacy of VEN.

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