Department of Pharmacy
Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931
Browse
5 results
Search Results
Item Can breakthroughs in dermal and transdermal macromolecule delivery surmount existing barriers and revolutionize future therapeutics?(Springer, 2025-05) Mittal, Anupama; Chitkara, DeepakThe delivery of macromolecules through dermal and transdermal routes presents both significant challenges and transformative opportunities in therapeutic applications. This review highlights the most recent advancements and innovative strategies aimed at overcoming the barriers associated with macromolecular delivery. Cutting-edge approaches such as the use of adjuvants (e.g., hyaluronic acid-based and chemical penetration enhancers), bioactive peptides with diverse functionalities, and mechanical force techniques—including iontophoresis, microneedles, and electroporation—are thoroughly explored. While various strategies have been implemented to enhance skin delivery, they often present significant challenges, particularly for macromolecules. Addressing these challenges requires integrating novel technologies and understanding the interplay between biological barriers and delivery mechanisms. Furthermore, the role of nanotechnology, through systems like nanoemulsions, polymeric nanoparticles, and transferosomes, is examined for its ability to protect macromolecules and regulate their release. Notably, this review provides unique perspectives on the interplay between these strategies and their potential to revolutionise future therapeutics. By highlighting key trends and advancements in macromolecule delivery, this review underscores the importance of innovative approaches in overcoming existing barriers and enabling efficient drug administration.Item Autophagy as a potential therapeutic target in regulating improper cellular proliferation(Frontiers Media, 2025-05) Chitkara, DeepakAutophagy is a degradative process that makes rapid turnover of old and impaired proteins and organelles possible. It is highly instigated by stress signals, like starvation, and contributes to the cell’s homeostasis. Autophagy performs a crucial function in keeping cell genomic integrity stable. Impaired autophagic flux is implicated in neurodegenerative diseases, abnormal ageing, and cancerous diseases. In diseases like cancer, autophagy performs a dualistic function; it can have both a tumor-suppressive and supportive role. Autophagy in the initial phases of tumorigenesis maintains the integrity of the genome and, if it fails, leads to cell death, thus having a tumor-suppressive role. Meanwhile, autophagy also imparts the function of the pro-survival mechanism in the latter stages of tumorigenesis and supports the cancerous cells in surviving conditions like hypoxia and increased oxidative stress. Autophagy also helps cancerous cells develop drug resistance in some cases. Thus, modulation of the autophagic mechanism is a possible therapeutic strategy in cancer therapy as its inhibition can sensitise cancer cells to anti-cancerous drugs. The promotion of autophagy, in some cases, can also safeguard cells from toxic protein aggregation and enhanced oxidative stress. Excessive autophagy can result in autophagic cell death. Autophagy also regulates several cellular processes and cell death pathways, like apoptosis. Therefore, an in-depth knowledge of the autophagy process and its regulating molecules is critically important. Pharmaceutical small molecules or cellular target modulation can help modulate the cellular autophagy process in the context of specific disease conditions.Item Simultaneous estimation of rapamycin, temozolomide and its metabolites using UPLC-ESI-MS/MS and its application to pharmacokinetics in C6-glioma bearing animals(Elsevier, 2025-09) Mittal, Anupama; Chitkara, DeepakTherapeutic drug monitoring (TDM) plays a crucial role in the optimization of drug dosage profiles and establishing an optimal balance between toxicity and its effectiveness. Developing TDM methods for simultaneous estimation of multiple molecules with diverse physiochemical properties is quite complicated and difficult to achieve. Thus, hindering the quantitative estimation for TDM and in-depth analysis from bench to clinical settings. Therefore, the current study reports a bioanalytical method for the simultaneous determination of anticancer and immunosuppressant molecules (namely rapamycin, temozolomide, and its metabolites) in a single injection using whole blood as a biological matrix.Item cRGD-functionalized nanohybrid conjugates codelivering temozolomide and rapamycin for treating Glioblastoma multiforme: in vitro and in vivo evaluation(ACS, 2025-10) Mittal, Anupama; Chitkara, DeepakThe conventional treatment of glioblastoma multiforme primarily uses Temozolomide as a chemoadjuvant alongside debulking surgery and radiotherapy; however, resistance, as well as tumor recurrence, remains a common outcome. Employing combination therapy to target multiple pathways while improving delivery with advanced systems has always been sought after. Herein, we report cRGD-functionalized hybrid polymeric nanoconjugates that could deliver Temozolomide (TMZ) and rapamycin (RAP) (cRGD-Hybrid TMZ/R NCs) as a dual payload. The cRGD-Hybrid TMZ/R NCs were thoroughly characterized, exhibiting a particle size and surface zeta potential of 141.83 nm (PDI 0.233) and −0.168 mV, respectively. The nanoconjugates carrying TMZ and RAP as dual payloads were initially screened for synergism by determining their combination index in C6 and U87MG glioma cells. Further, in vitro cell-based assays showed improved cellular uptake, cytotoxicity, and apoptotic potential of hybrid nanoconjugates. Thereafter, the cRGD-Hybrid TMZ/R NCs were evaluated in a C6-cell-induced syngeneic orthotropic glioma model in Sprague–Dawley rats, exhibiting an improved therapeutic outcome including, reduced hemispherical width (RH/LH) ratios, tumor burden, and improved survival rates compared to the free drug(s) counterpart. The histopathological evaluation indicated no major sign of toxicity in vital organs such as heart, lungs, liver, kidney, and spleen, affirming the biocompatibility of the developed cRGD-Hybrid TMZ/R nanoconjugates. In conclusion, amalgamating the cRGD cell-penetrating peptide with polymer hybrid nanoconjugates presents a better approach for delivering multiple payloads in the treatment of GBM.Item Lipopolymeric nanoplex-mediated CRISPR/Cas9 delivery for VEGF-A knockdown in psoriatic angiogenesis(ACS, 2025-10) Yadav, Sushil; Mittal, Anupama; Chitkara, DeepakPsoriasis is a chronic, incurable inflammatory skin disease characterized by immune cell infiltration, aberrant keratinocyte differentiation, and enhanced angiogenesis. Overexpression of the vascular endothelial growth factor-A (VEGF-A) gene promotes angiogenesis and is essential for endothelial cell migration, adhesion, and proliferation. Therefore, downregulating VEGF-A represents a promising therapeutic strategy for angiogenesis-related disorders. We investigated the application of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) ribonucleoprotein complexes (sgRNA/eGFP-Cas9 RNPs) targeting VEGF-A in psoriasis. To enable efficient delivery in vitro and in vivo, we developed lipopolymeric nanoplexes (NPXs) encapsulating sgRNA/eGFP-Cas9 RNPs. These NPXs exhibited a particle size of 142.2 nm (polydispersity index: 0.144), a zeta potential of +4.27 mV, and achieved >70% transfection efficiency in HaCaT (human immortalized keratinocyte) cells. Ex vivo skin permeation studies demonstrated 66% of permeation after 24 h. The optimized NPX formulation was incorporated into a Carbopol-based gel, which displayed non-Newtonian, shear-thinning behavior with variable thixotropy and achieved 48% of skin permeation after 24 h. In vivo efficacy assessment in an imiquimod-induced psoriasis model in Swiss albino mice showed significantly improved Psoriasis Area and Severity Index (PASI) scores, reduced epidermal damage, and suppressed keratinocyte proliferation compared to naked RNPs and blank gel controls. Gene editing analysis revealed an indel frequency of 40.7% by T7 endonuclease I assay and 14% by Sanger sequencing. Enhanced cellular uptake, efficient skin permeation and retention, and improved therapeutic efficacy collectively highlight the potential of NPX-mediated CRISPR/Cas9 delivery as a noninvasive strategy for psoriasis treatment.