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Item Enhancing 3-acetyl-11-keto-β-boswellic acid skin permeation via nanostructured lipid carriers: integrating quality by design principles for risk estimation and optimization(RSC, 2025-10) Taliyan, Rajeev; Singhvi, Gautam3-Acetyl-11-keto-β-boswellic acid (AKBA), a bioactive compound derived from Boswellia serrata, exhibits significant anti-inflammatory and antioxidant properties, making it a promising candidate for treating inflammatory skin disorders. Its hydrophobic nature makes topical administration challenging. By developing nanostructured lipid carriers (NLCs), this work sought to enhance the skin penetration of AKBA. Quality-by-design principles were applied for the development of a robust formulation, where AKBA-NLCs were developed using a three-factor, three-level Box–Behnken design. AKBA-NLCs were prepared by the hot homogenization technique. The optimized formulation was further loaded into a gelling system, and its rheological parameters were evaluated. Further evaluation for ex vivo skin permeation and retention, along with other characteristics such as occlusivity, extrudability, and spreadability, was performed. Quality-by-design through p-value assessment highlighted that all three factors significantly affected particle size, and in the case of PDI, only lipid content showed a significant impact, whereas for entrapment efficiency, lipid and surfactant content were the governing factors. Based on the set constraints, the optimized batch of AKBA-NLCs exhibited a particle size of 173.700 ± 1.165 nm, a PDI of 0.323 ± 0.012, a zeta potential of −19.533 ± 0.493 mV, and an entrapment efficiency of 82.349 ± 3.223%. The in vitro release showed a prolonged release profile up to 56 h. When tested for cytotoxicity in the HaCaT cell line, the formulation was observed to be non-cytotoxic. The rheological data of the gel demonstrated a non-Newtonian, pseudo-plastic nature and indicated good structural strength. The ex vivo skin permeation of AKBA-NLCs was found to be 1.34 times higher than that via plain gel. Based on consistent results of viscosity, particle size integrity, and assay after one year of storage, the formulation was found to be stable. The formulation method used was simple and cost-effective, allowing for possible industrial scale-up. According to the findings, the NLC-loaded gel may prove to be a useful delivery strategy for the management of inflammatory skin conditions.Item The role of diet and nutraceuticals in the amelioration of multidrug resistance amongst cancer patients(Springer, 2025-11) Singhvi, Gautam; Taliyan, RajeevCancer is one of the leading causes of death globally, with the reported numbers rising every year. Although the medical fraternity has made considerable progress in early detection and treatment interventions, the numbers are expected to increase drastically by 2040. The most prevalent cause of mortality in people with diverse cancer types is likely multidrug resistance (MDR). As per recent reports, there have been increased incidences of cancer being reported globally, with projections of low-Human Development Index (HDI) countries being affected more in the near future.Item Targeting rheumatoid arthritis: a molecular perspective on biologic therapies and clinical progress(Springer, 2025-07) Jain, Ankit; Singhvi, GautamTo surpass challenges with traditional approaches to treat Rheumatoid arthritis (RA), an improved understanding of molecular-level pathogenesis brought forth targeted therapy with biologics as a great promise in halting the progression of RA. Novel biologics are being designed with the help of synthetic fusion proteins, monoclonal antibodies, and protein fragments, with or without drugs, to target various signaling pathways, including TNF-α, IL-6, JAK, Th-17, IL-family, GM-CSF, B-cell, and T-cell signaling. The journey of biologics in RA management began in 1998 with etanercept (Enbrel®). Since then, regulatory bodies have endorsed various biologics and many more are in different clinical stages. This review aims to explore RA by examining current clinical studies with focus on emerging development on molecular-level pathogenesis, prevalent conventional treatment options and their limitations, as well as recent advancements in biologically engineered therapeutics. It also includes a few relevant case studies to support these findings. Despite the progress, challenges remain, such as high costs and the need for safer, more effective delivery methods. The document also touches on the historical perspective of RA, its pathophysiology, and the role of synovial fluid pharmacokinetics in treatment effectiveness. The importance of early diagnosis and well-controlled treatment strategies for RA is paramount. The potential of emerging biological and targeted treatments to facilitate a treat-to-target approach in RA management is substantial. This review explores the key molecular pathways of rheumatoid arthritis and includes detailed figures for better understanding. It also highlights the promising potential of biologically engineered therapeutics, supported by evidence from case studies and clinical trials.Item Development of gene expression inhibitors for the treatment of cutaneous carcinomas(Taylor & Francis, 2025-07) Roy, Aniruddha; Singhvi, GautamCutaneous carcinoma is one of the most common cancers worldwide, with rising incidence and mortality rates, especially among white Caucasians. It primarily includes non-melanoma skin cancer (NMSC) and melanoma skin cancer (MSC), which together account for over 90% of all skin cancers. The main cause is the abnormal proliferation of skin cells due to genetic mutations and environmental damage [Citation1]. Basal cell carcinoma (BCC) arises from mutations in the Ptch1 tumor suppressor gene caused by UV-radiations, leading to dysregulated hedgehog signaling, while Squamous cell Carcinoma (SCC), which originates in keratinocytes, is driven by TP53 mutations and epigenetic changes. In melanoma, mutations in genes like B-Raf proto-oncogene, serine/threonine kinase (BRAF), Neuroblastoma RAS Viral Oncogene Homolog (NRAS), Neurofibromin 1 (NF1), or proto-oncogene receptor tyrosine kinase (KIT) activate the MAPK pathway, leading to cellular proliferation and invasion. Traditional treatments, such as surgery, chemotherapy, and immunotherapies, face challenges like resistance, side effects, and don’t address widespread epigenetic alterations that activate oncogenes and silence tumor suppressors, emphasizing the need for targeted genetic therapies to inhibit skin cancer growth [Citation2]. Several gene expression inhibitors are being explored for cutaneous carcinomas, such as DNMT inhibitors (guadecitabine and decitabine, etc), which reverses abnormal DNA methylation to reactivate tumor suppressor genes, while EZH2 inhibitors (CPI-1205) block H3K27 trimethylation to prevent oncogenic gene silencing. HDAC inhibitors (entinostat, mocetinostat, and panobinostat), enhance histone acetylation to promote tumor suppressor expression and improve immune responses, and siRNA-based therapies (STP705 and c-Myc siRNA, etc) or antisense oligonucleotides targeting lncRNAs like MALAT1 and TINCR directly silence cancer-promoting genes and disrupt oncogenic pathways [Citation3]. Therefore, recent investigations focused on the regulation of gene expression and the development of their inhibitors as effective targeted therapeutic strategies for the treatment of cutaneous carcinoma.Item Influence of nanocarrier additives on biomechanical response of a rat skin(IEEE, 2024-10) Rao, Venkatesh K.P.; Singhvi, GautamSkin health monitoring focuses on identifying diseases by assessing the mechanical properties of the skin. These properties may degrade with time, which can alter the skin’s natural frequencies and the modeshapes associated with those frequencies. Exploring the skin’s mechanical properties can enhance our understanding of its dynamics, improving clinical trials and diagnostics. In this work, the dynamics of the skin were measured using a laser-based non-invasive optical sensor experiment. We measured the skin’s mechanical properties over time by analyzing its resonant frequencies and mode shapes. A nanocarrier gel and ketoconazole cream were topically applied to keep the skin hydrated and facilitate deeper penetration of the additives in the skin. Time-based research was used to assess the effect of different formulations on skin elasticity. Experimental results for the modulus of elasticity were compared with those obtained using Finite Element Analysis (FEA) simulations. We observed a reduction in frequencies of cream and gel-treated skin by 29.98% and 44.029%, respectively, compared to normal skin (frequency: 263.3±1.18 Hz and Modulus of elasticity: 7.56±2.60 MPa). A decrease in stiffness is attributed to increased water content, was observed in cream- and nanocarrier gel-treated skin compared to normal skin. Experimental and numerical results are found to be consistent with one another. This optical sensor-based approach has the potential for studying diseased skin mechanics and its response to gel and cream treatments, aiming to reduce skin disorder morbidity and severity.Item Formulating ternary inclusion complex of sorafenib tosylate using β-cyclodextrin and hydrophilic polymers: physicochemical characterization and in vitro assessment(Springer, 2022-09) Marathe, Sandhya Amol; Singhvi, GautamSorafenib tosylate (SFNT) is the first-line drug for hepatocellular carcinoma. It exhibits poor solubility leading to low oral bioavailability subsequently requiring intake of large quantities of drug to exhibit desired efficacy. The present investigation was aimed at enhancing the solubility and dissolution rate of SFNT using complexation method. The binary inclusion complex was prepared with β-cyclodextrin (β-CD). The molecular docking studies confirmed the hosting of SFNT into hydrophobic cavity of β-CD, while the phase solubility studies revealed the stoichiometry of complexation with a stability constant of 735.8 M−1. The ternary complex was prepared by combining the SFNT-β-CD complex with PEG-6000 and HPMC polymers. The results from ATR-IR studies revealed no interaction between drug and excipients. The decreased intensities in ATR-IR peaks and changes in chemical shifts from NMR of SFNT in complexes indicate the possibility of SFNT hosting into the hydrophobic cavity of β-CD. The disappearance of SFNT peak in DSC and XRD studies revealed the amorphization upon complexation. The ternary complexes exhibited improved in vitro solubility (17.54 µg/mL) compared to pure SFNT (0.19 µg/mL) and binary inclusion complex (1.52 µg/mL). The dissolution profile of ternary inclusion complex in 0.1 N HCl was significantly higher compared to binary inclusion complex and pure drug. In cytotoxicity studies, the ternary inclusion complex has shown remarkable effect than the binary inclusion complex and pure drug on HepG2 cell lines.Item Immunological challenges and opportunities in glioblastoma multiforme: A comprehensive view from immune system lens(Elsevier, 2024-11) Singhvi, Gautam; Taliyan, RajeevGlioblastoma multiforme (GBM), also known as grade IV astrocytoma, is the most common and deadly brain tumour. It has a poor prognosis and a low survival rate. GBM cells' immunological escape mechanism helps them resist advanced multimodal therapy. In physiological homeostasis, brain astrocytes and microglia suppress infections and clear the potential pathogen from the system. However, in severe pathological conditions like cancer, the immune response fails to eliminate mutated and rapidly over-proliferating GBM cells. The malignant cells' interactions with immune cells and the neoplasm's immunosuppressive environment enable the avoidance and their clearance. Immunotherapy efficiently addresses these difficulties, as shown by sufficient evidence. This review discusses how GBM cells inhibit and elude the immune system. These include MHC molecule expression alteration and PD-L1 and CTLA-4 immune checkpoint overexpression. Without co-stimulation, these changes induce effector T-cell tolerance and anergy. The review also covers how MDSCs, TAMs, Herpes Virus Entry Mediators, and Human cytomegalovirus protein decrease the effector immune response against glioblastoma. The latter part discusses various therapies that are available in the market or under clinical trials which revolves around combating resistance against the available multimodal therapies. The recent trends indicate that there are various monoclonal antibodies and peptide-based vaccines that can be utilized to overcome the immune evasion technique harbored by GBM cells.Item Photodynamic Therapy Induced Mitochondrial Targeting Strategies for Cancer Treatment: Emerging Trends and Insights(ACS, 2024-02) Chowdhury, Rajdeep; Singhvi, GautamThe perpetuity of cancer prevalence at a global level calls for development of novel therapeutic approaches with improved targetability and reduced adverse effects. Conventional cancer treatments have a multitude of limitations such as nonselectivity, invasive nature, and severe adverse effects. Chemotherapy is also losing its efficacy because of the development of multidrug resistance in the majority of cancers. To address these issues, selective targeting-based approaches are being explored for an effective cancer treatment. Mitochondria, being the moderator of a majority of crucial cellular pathways like metabolism, apoptosis, and reactive oxygen species (ROS) homeostasis, are an effective targeting site. Mitochondria-targeted photodynamic therapy (PDT) has arisen as a potential approach in this endeavor. By designing photosensitizers (PSs) that preferentially accumulate in the mitochondria, PDT offers a localized technique to induce cytotoxicity in cancer cells. In this review, we intend to explore the crucial principles and challenges associated with mitochondria-targeted PDT, including variability in mitochondrial function, mitochondria-specific PSs, targeted nanocarrier-based monotherapy, and combination therapies. The hurdles faced by this emerging strategy with respect to safety, optimization, clinical translation, and scalability are also discussed. Nonetheless, mitochondria-targeted PDT exhibits a significant capacity in cancer treatment, especially in combination with other therapeutic modalities. With perpetual research and technological advancements, this treatment strategy is a great addition to the arsenal of cancer treatment options, providing better tumor targetability while reducing the damage to surrounding healthy tissues. This review emphasizes the current status of mitochondria-targeted PDT, limitations, and future prospects in its pursuit of safe and efficacious cancer therapy.Item UV Spectrophotometric method for characterization of curcumin loaded nanostructured lipid nanocarriers in simulated conditions: Method development, in-vitro and ex-vivo applications in topical delivery(Elsevier, 2020-01) Pandey, Murali Monohar; Singhvi, GautamCurcumin the extract obtained from the dried rhizome of turmeric, Curcuma longa is a hydrophobic phenol that delivers numerous pharmacological actions like anti-inflammatory, anti-microbial and anti-oxidant, anti-psoriasis, antidiabetic, anticancer. But curcumin has low bioavailability issues that accompany low aqueous solubility, further, when administered orally, >90% of the drug degrades rapidly in the alkaline medium. Administering the drug topically can bypass the problem as well as first-pass metabolism and therefore delivering the drug at the targeted site of action. Encapsulating curcumin in nanostructured lipid nanocarriers (NLC) is an excellent novel strategy. Further, these NLC provides both the controlled release and helps in the enhanced permeation of the drug through the skin's physiological barrier, stratum corneum. For the NLC characterization, a reliable method must be developed that can accurately and precisely determine the drug content in the formulation and also for its in-vitro and ex-vivo characterization. This experiment describes the analytical validation parameters described as per International Conference of Harmonization guidelines to develop a method using the UV–Visible spectroscopy. The method was developed in two solvent systems i.e. methanol and 6.4 pH phosphate buffer with 1.5% polysorbate 80. Methanol solvent was used for the determination of curcumin in the NLC formulation via determining the encapsulation efficiency and 6.4 pH phosphate buffer with 1.5% polysorbate 80 solvent was used for in-vitro and ex-vivo characterization of the developed NLC formulation (cream and gel). These methods were validated in response to linearity, the limit of detection, the limit of quantification, precision, accuracy, repeatability, and specificity.Item UV Spectrophotometric method for characterization of curcumin loaded nanostructured lipid nanocarriers in simulated conditions: Method development, in-vitro and ex-vivo applications in topical delivery(Elsevier, 2020-01) Pandey, Murali Monohar; Singhvi, GautamCurcumin the extract obtained from the dried rhizome of turmeric, Curcuma longa is a hydrophobic phenol that delivers numerous pharmacological actions like anti-inflammatory, anti-microbial and anti-oxidant, anti-psoriasis, antidiabetic, anticancer. But curcumin has low bioavailability issues that accompany low aqueous solubility, further, when administered orally, >90% of the drug degrades rapidly in the alkaline medium. Administering the drug topically can bypass the problem as well as first-pass metabolism and therefore delivering the drug at the targeted site of action. Encapsulating curcumin in nanostructured lipid nanocarriers (NLC) is an excellent novel strategy. Further, these NLC provides both the controlled release and helps in the enhanced permeation of the drug through the skin's physiological barrier, stratum corneum. For the NLC characterization, a reliable method must be developed that can accurately and precisely determine the drug content in the formulation and also for its in-vitro and ex-vivo characterization. This experiment describes the analytical validation parameters described as per International Conference of Harmonization guidelines to develop a method using the UV–Visible spectroscopy. The method was developed in two solvent systems i.e. methanol and 6.4 pH phosphate buffer with 1.5% polysorbate 80. Methanol solvent was used for the determination of curcumin in the NLC formulation via determining the encapsulation efficiency and 6.4 pH phosphate buffer with 1.5% polysorbate 80 solvent was used for in-vitro and ex-vivo characterization of the developed NLC formulation (cream and gel). These methods were validated in response to linearity, the limit of detection, the limit of quantification, precision, accuracy, repeatability, and specificity.