Department of Pharmacy
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Item Neurotensin conjugated polymeric porous microparticles suppress inflammation and improve angiogenesis aiding in diabetic wound healing(Wiley, 2024-11) Chitkara, Deepak; Mittal, AnupamaNeurotensin (NT), a bioactive tridecapeptide aids in diabetic wound healing by modulating inflammation and angiogenesis. However, its rapid degradation in peptidase-rich wound environment (plasma half-life <2 min) limits its efficacy. To address this, neurotensin-conjugated polymeric porous microparticles (NT-PMP) were developed and loaded in gelatin (hydrogel 15% w/v) for topical application, enabling sustained NT release to enhance therapeutic outcomes. NT-PMP exhibited a size range of 60 – 240 µm (mean: 120.63 ± 40.71 µm) and pore size of 5 – 16 µm (average: 10.68 ± 3.47 µm). In vitro studies demonstrated cytocompatibility of NT-PMP in fibroblasts and reduced TNF-α levels in inflammation-induced macrophages (1256 ± 167.02 pg/ml). Further NT-PMP scaffold depicted excellent cell adhesion and migration properties upon seeding of dermal fibroblasts on surface of PMPs. In vivo studies in diabetic wound rat model demonstrated effective wound management, characterized by notable regenerative and healing attributes in the presence of NT-PMP. This included complete re-epithelialization, reducing pro-inflammatory cytokine (TNF-α), and enhancing VEGF expression, ultimately leading to the development of a well-organized collagen matrix in diabetic wounds upon application of NT-PMP gel.Altogether, NT conjugated PMP loaded in hydrogel demonstrated significant regenerative and healing properties, suggesting its potential as an alternative treatment for diabetic wounds.Item Targeting the epigenome with advanced delivery strategies for epigenetic modulators(AIChE, 2024-08) Chitkara, Deepak; Pandey, Murali Monohar; Mittal, AnupamaEpigenetics mechanisms play a significant role in human diseases by altering DNA methylation status, chromatin structure, and/or modifying histone proteins. By modulating the epigenetic status, the expression of genes can be regulated without any change in the DNA sequence itself. Epigenetic drugs exhibit promising therapeutic efficacy against several epigenetically originated diseases including several cancers, neurodegenerative diseases, metabolic disorders, cardiovascular disorders, and so forth. Currently, a considerable amount of research is focused on discovering new drug molecules to combat the existing research gap in epigenetic drug therapy. A novel and efficient delivery system can be established as a promising approach to overcome the drawbacks associated with the current epigenetic modulators. Therefore, formulating the existing epigenetic drugs with distinct encapsulation strategies in nanocarriers, including solid lipid nanoparticles, nanogels, bio-engineered nanocarriers, liposomes, surface modified nanoparticles, and polymer–drug conjugates have been examined for therapeutic efficacy. Nonetheless, several epigenetic modulators are untouched for their therapeutic potential through different delivery strategies. This review provides a comprehensive up to date discussion on the research findings of various epigenetics mechanism, epigenetic modulators, and delivery strategies utilized to improve their therapeutic outcome. Furthermore, this review also highlights the recently emerged CRISPR tool for epigenome editing.Item Recent advancements in lipid based nanocarrier systems for the treatment of wounds(Elsevier, 2025) Chitkara, Deepak; Mittal, AnupamaWound healing is a complex and dynamic process that involves a well-coordinated interaction between various immunological and biological systems. Various active pharmaceutical ingredients delivered in the form of ointments and creams are available in the market. However, the major setbacks associated with these delivery systems include poor permeation and rapid degradation of active pharmaceutical ingredients in harsh wound environment. Therefore lipid-based nanocarrier systems have emerged as a promising approach for topical drug delivery in wound healing. The major advantages associated with these carriers are biocompatibility, biodegradability, high encapsulation efficiency, enhanced cellular uptake, controlled-release profile, and better tissue penetration. Moreover, lipid-based nanocarriers can accommodate both hydrophilic and hydrophobic therapeutic molecules, including small molecules, proteins, peptides, and growth factors, depending on the nature and content of lipids used to prepare lipid-based nanocarriers. Recently, lipid nanoparticles have been extensively explored for mRNA delivery, which upregulate/downregulate the target proteins that aid in accelerated healing in chronic wounds. This chapter summarizes the recent advancements in lipid-based nanocarriers in delivering small molecules and macromolecules for treating various types of wounds.Item Enhancing temozolomide in vivo stability and efficacy through hybrid nanoconjugate approach for improved glioblastoma multiforme treatment(Elsevier, 2025-01) Chitkara, Deepak; Mittal, AnupamaTemozolomide (TMZ) is considered as a standard-of-care DNA alkylating agent for treating glioblastoma multiforme. Despite being a highly potent molecule, TMZ poses several limitations, including short half-life, rapid metabolism, low brain bioavailability and dose-dependent toxicities. Attempts have been made to improve the delivery of TMZ that showed nominal therapeutic outcomes. In the current study, we have conjugated TMZ to mPEG-b-P(CB-{g-COOH} copolymer to obtain mPEG-b-P(CB-{g-COOH; g-TMZn} that demonstrated improvement in stability and efficacy. Further, a hybrid TMZ nanoconjugate formulation was developed using mPEG-b-P(CB-{g-COOH; g-TMZ40} and mPEG-polylactic acid (mPEG-PLA) that showed an average size of 105.7 nm with narrow PDI of <0.2 and TMZ loading of 21.6%. Stability was assessed under physiological conditions wherein TMZ was found to be stable with a half-life of ∼194 h compared to 1.8 h for free TMZ. The Hybrid TMZ nanoconjugates showed improved intracellular uptake and reduced IC50 values in C6 and U87MG glioma cells. Further, they exhibited better in vivo therapeutic outcome, i.e., reduced brain weight, hemispherical width ratio and improved survival rate in C6-cell induced orthotropic glioma model in Sprague Dawley rats compared to the free TMZ-treated and positive control animals. Histopathological evaluation also revealed reduced cell infiltration in the lungs and reduced toxicity in major organs. Overall, the hybrid nanoconjugates of TMZ significantly improved its stability and efficacy in the GBM model, thereby opening newer avenues for treatment.Item Immunocyte Derived Exosomes: Insight into the Potential Chemo-immunotherapeutic Nanocarrier Targeting the Tumor Microenvironment(ACS, 2022-12) Mittal, Anupama“Cancer” is a dreadful immune-pathological condition that is characterized by anti-inflammatory and tumorigenic responses, elicited by the infiltrating immune cells in the vicinity of an uncontrollably proliferative tumor in the tumor microenvironment (TME). The TME offers a conducive microenvironment that supports cancer cell survival by modulating the host immune defense. Recent advancement in exosomal research has shown exosomes, originating from immune cells as well as the cancer cells, have immense potential for suppressing cancer progression and survival in the TME. Additionally, exosomes, irrespective of their diverse sources, have been reported to be efficient nanocarriers for cancer therapeutics with the ability for targeted delivery due to their biogenic nature, ease of cellular uptake, and scope for functionalization with biomolecules like peptides, aptamers, targeting ligands, etc. Immune cell-derived exosomes per se have been found efficacious against cancer owing to their immune-stimulant properties (in either naive or antigen primed form) even without loading any of cancer therapeutics or targeting ligand conjugation. Nevertheless, exosomes are being primarily explored as nanovesicular carriers for therapeutic molecules with different loading and targeting strategies, and the synergism between immunotherapeutic behavior of exosomes and the anticancer effect of the therapeutic molecules is yet to be explored. Hence, this review focuses specifically on the possible strategies to modulate the immunological nature of the source immune cells to obtain immune stimulant exosomes and bring these into the spotlight as chemo-immunotherapeutic nanovesicles, that can easily target and modulate the TME.Item Pramlintide an Adjunct to Insulin Therapy: Challenges and Recent Progress in Delivery(ASPET, 2024-01) Mittal, Anupama; Chitkara, DeepakDysregulation of various glucoregulatory hormones lead to failure of insulin monotherapy in patients with diabetes mellitus due to various reasons, including severe hypoglycemia, glycemic hypervariability, and an increased risk of microvascular complications. However, pramlintide as an adjunct to insulin therapy enhances glucagon suppression and thereby offers improved glycemic control. Clinical studies have shown that pramlintide improves glycemic control, reduces postprandial glucose excursions, and promotes weight loss in patients with type 1 and type 2 diabetes. Although clinical benefits of pramlintide are well reported, there still exists a high patient resistance for the therapy, as separate injections for pramlintide and insulin must be administered. Although marketed insulin formulations generally demonstrate a peak action in 60–90 minutes, pramlintide elicits its peak concentration at around 20–30 minutes after administration. Thus, owing to the significant differences in pharmacokinetics of exogenously administered pramlintide and insulin, the therapy fails to elicit its action otherwise produced by the endogenous hormones. Hence, strategies such as delaying the release of pramlintide by using inorganic polymers like silica, synthetic polymers like polycaprolactone, and lipids have been employed. Also, approaches like noncovalent conjugation, polyelectrolyte complexation, and use of amphiphilic excipients for codelivery of insulin and pramlintide have been explored to address the issues with pramlintide delivery and improve patient adherence to the therapy. This approach may usher in a new era of diabetes management, offering patients multiple options to tailor their treatment and improve their quality of lifeItem Physiological, Biochemical, and Gene Expression Responses of Sugarcane Under Cold, Drought and Salt Stresses(Springer, 2022-11) Mittal, AnupamaThe quantitative nature of abiotic stresses makes the understanding of its molecular basis a demanding task. For developing a rational breeding and/or genetic engineering strategy—understanding the environmental signal perception, its transmission to cellular machinery and adaptive responses of the plant is critical. Here, subjecting sugarcane seedlings to salt and cold stresses resulted in chlorosis, wilting, leaf rolling and the drought stress led to decrease in relative water content. The LPO content accumulated during drought and salt stress indicate the stress responses of the plant. The proline content increased in response to drought and salt stress underscore the proline function as an important osmoprotectant in sugarcane. The differential gene expression under drought, salt and cold stress for abiotic stress responsive genes like p5CS1, APX, CAT, GST, HSP, LEA, NAC, SOD, NHX, NFY, NCED, ERA, SOS, and DREB in sugarcane seedlings indicates the molecular basis of stress response in this commercially important crop.Item Molecular medicines for cancer: concepts and applications of nanotechnology(CRC Press, 2019) Chitkara, Deepak; Mittal, AnupamaThe field of molecular medicine covers the medical interventions targeting molecular structures and mechanisms that are involved in disease progression. In cancer, several molecular mechanisms have been shown to impact its progression, aggressiveness and chemoresistance. Increasing evidence demonstrates the role of nanotechnology and outcome of molecular therapy. Several books have discussed molecular biology and mechanisms involved in cancer, but this text gives an account of molecular therapeutics in cancer relating to advancements of nanotechnology. It provides a description of the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnology. Key Features: Provides current information in the multidisciplinary field of molecular medicines and its targeted delivery to cancer using nanotechnology Presents important aspects of nanotechnology in the site-specific delivery of anticancer agents Includes up to date information on oligonucleotide and gene based therapies in cancer Describes small targeted molecules, antibodies and oligonucleotides which have shown to selectively target the molecular structures thereby influencing signal transduction Facilitates discussion between researchers involved in cancer therapy and nanoscientistsItem Delhi's network for surveillance of antimicrobial resistance: The journey, challenges and output from first year(Elsevier, 2023-02) Mittal, AnupamaAntimicrobial resistance [AMR] has emerged as a global and national priority and establishing an effective surveillance system for antimicrobial resistance is an essential prerequisite for generating evidence for informed policymaking at both national and state levels.Item P-15 functionalized porous microspheres as biomimetic habitats for bone tissue engineering applications(Wiley, 2010-10) Mittal, AnupamaPoly(L-lactide-co-ε-caprolactone) (PLCL, 75/25) solid and porous microspheres (MS) were prepared using solvent evaporation and gas foaming method, respectively. These MS were characterized for particle size, surface morphology, porosity, and surface area. Porous MS were modified by P-15 peptide using carbodiimide coupling method. These unmodified solid and P-15-modified/-unmodified porous MS were further evaluated for MG-63 proliferation, cell alignment, collagen type I expression, and matrix mineralization for 21 days. In vitro cell culture studies of P-15 functionalized porous MS exhibited enhanced cell viability, increased formation of actin filament bundles and collagen type I expression as compared to solid MS and 2D (polystyrene 24 well plate), and maintained the mineralization potential of MG-63 cells. The results suggests P-15-modified porous PLCL MS were able to grow the cells with proper cell functionality and hold potential to be used as an injectable cell carrier for bone tissue engineering applications.