BITS Faculty Publications
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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.Item Unlocking the potential of photodynamic therapy in Psoriasis: Mechanistic insights, wide-ranging applications, challenges and future directions(Elsevier, 2025-10) Rao, Venkatesh K.P.; Jain, Ankit; Rao, Venkatesh K.P.Psoriasis is an autoimmune skin disorder involving the interaction of genetic factors and environmental stress which leads to uncontrolled proliferation of keratinocytes and activation of the immune system. Conventional treatment options, including topical therapies, phototherapy, systemic drugs, and biologics, are used based on disease severity. Recently, photodynamic therapy (PDT) has gained attention due to its unique advantages over traditional treatments. PDT relies on three key components i.e. photosensitizer (PS) administered either locally or systemically, specific light irradiation, and molecular oxygen to generate reactive oxygen species (ROS), leading to the damage of photoactivated cells through cellular apoptosis and necrosis. Recent studies have explored innovative PSs and delivery strategies to enhance the efficacy of PDT in psoriasis. Emerging research highlights the potential of PDT to suppress keratinocyte proliferation and modulate inflammatory pathways, such as JAK/STAT inhibition via ROS-mediated upregulation of SOCS1/3. Innovative delivery strategies and photosensitizers, including chlorin e6, IR820, ZnPc-F7, and 5-aminolevulinic acid (ALA), have been developed to enhance selectivity, reduce treatment-associated discomfort, and improve skin penetration. Nanocarrier systems, such as mesoporous silica nanoparticles, polydopamine-based platforms, and lipid-based nanocarriers, have enabled synergistic photochemotherapy and dual photothermal-photodynamic approaches, leading to improved therapeutic outcomes by inducing apoptosis, restoring skin barrier function, and attenuating proinflammatory signaling. This review highlights PDT principles, mechanisms, approved PSs, and emerging combinations. Despite its promising effects, PDT remains underutilized in psoriasis, demanding further research and nanotech-driven optimization for patient-friendly therapies.Item Eugenol-loaded lipid nanoparticles-derived hydrogels ameliorate psoriasis-like skin lesions by lowering oxidative stress and modulating inflammation(ACS, 2024-10) Chitkara, DeepakPsoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, overproliferation of keratinocyte, disruption of epidermal cell differentiation, and increased blood vessel growth in the dermal layer. Despite the common use of corticosteroids in psoriasis treatment, their limited efficacy and numerous side effects pose significant challenges. This research introduces a promising alternative approach by encapsulating eugenol (EU) in soya phosphatidylcholine (SPC) nanoparticles (EUNPs) which showed spherical shape nanoparticles with a hydrodynamic size of approximately 200 nm, polydispersity index 0.23, encapsulation efficiency of 85% having good colloidal stability indicated by ζ-potential of −27 mV. Later on, these EUNPs were formulated into a topical hydrogel system by using Carbopol 974P (EUNPGel), which exhibited superior drug loading, enhanced release kinetics for 48 h, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs inhibited keratinocyte proliferation, induced apoptosis, and augmented the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions demonstrated effective dermal penetration, suppressed keratinocyte hyperplasia and restored epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3.75 to 0.5 within 5 days. This novel approach enhances ROS scavenging capacity, improves cellular uptake, facilitates skin penetration and retention, reduces the activity of hyperactive immune cells, and suggests potential applications for treating other immune-related disorders such as acne and atopic dermatitis.Item Apremilast loaded lyotropic liquid crystalline nanoparticles embedded hydrogel for improved permeation and skin retention: An effective approach for psoriasis treatment(Elsevier, 2023-06) Singhvi, Gautam; Roy, AniruddhaThe present work aimed to prepare and evaluate Apremilast loaded lyotropic liquid crystalline nanoparticles (LCNPs) formulation for skin delivery to enhance the efficacy with reduced adverse effects of the oral therapy in psoriasis treatment. The LCNPs were prepared using the emulsification using a high shear homogenizer for size reduction and optimized with Box Behnken design to achieve desired particle size and entrapment efficiency. The selected LCNPs formulation was evaluated for in-vitro release, in-vitro psoriasis efficacy, skin retention, dermatokinetic, in-vivo skin retention, and skin irritation study. The selected formulation exhibited 173.25 ± 2.192 nm (polydispersity 0.273 ± 0.008) particle size and 75.028 ± 0.235% entrapment efficiency. The in-vitro drug release showed the prolonged-release for 18 h. The ex-vivo studies revealed that LCNPs formulation exhibited drug retention up to 3.2 and 11.9-fold higher, in stratum corneum and viable epidermis compared to conventional gel preparation. In-vitro cell line studies performed on immortal keratinocyte cells (HaCaT cells) demonstrated non-toxicity of selected excipients used in designed LCNPs. The dermatokinetic study revealed the AUC0–24 of the LCNPs loaded gel was 8.4 fold higher in epidermis and 2.06 fold in dermis, respectively compared to plain gel. Further, in-vivo animal studies showed enhanced skin permeation and retention of Apremilast compared to conventional gel.Item Nanocarriers for topical delivery in psoriasis(Elsevier, 2020) Singhvi, GautamPsoriasis is a chronic autoimmune skin disorder that affects millions of people across the planet. It causes many serious complications to afflicted patients and is indicated by uncontrolled growth and differentiation of keratinocytes. Conventional dosage forms have been used for the topical delivery of antipsoriatic drugs but they possess their own limitations. These include poor patient compliance, inadequate penetration and targeting to diseased skin, and local toxicity. In recent decades nanocarriers like liposomes, micelles, and solid lipid nanoparticles have shown potential in delivering antipsoriatic active compounds to the targeted areas of skin. Such novel formulations improve therapeutic efficacy, increase localization of drug in the skin, and decrease side effects. This chapter sheds light on the current advancements in the field of nanocarriers in treating the psoriatic skin condition.Item Emerging landscape in psoriasis management: From topical application to targeting biomolecules(Elsevier, 2018-10) Singhvi, GautamPsoriasis is a chronic autoimmune skin disorder affecting 2–3% of the world population. It has characteristic features such as increased keratinocyte proliferation and production of inflammatory mediators. The treatment involves various strategies including topical, systemic, phototherapy and biologics. Topical therapies are preferred for mild to moderate psoriasis conditions over the systemic therapies which are ideal in severe disease conditions. The systemic therapies include immunosuppressants, biological agents and recently approved phosphodiesterase-4 (PDE4) inhibitors. There are various limitations associated with the existing therapies where the new findings in the pathogenesis of psoriasis are paving a path for newer therapeutics to target at the molecular level. Various small molecules, PDE-4 inhibitors, biologics, and immunomodulator proved efficacious including the new molecules targeting Janus kinases (JAK) inhibitors that are under investigation. Furthermore, the role of genetic and miRNAs in psoriasis is still not completely explored and may further help in improving the treatment efficacy. This review provides an insight into various emerging therapies along with currently approved treatments for psoriasis.Item Psoriasis: pathological mechanisms, current pharmacological therapies, and emerging drug delivery systems(Elsevier, 2020-12) Singhvi, GautamPsoriasis is a chronic autoimmune skin disorder triggered by either genetic factors, environmental factors, life style, or a combination thereof. Clinical investigations have identified pathogenesis, such as T cell and cytokine-mediated, genetic disposition, antimicrobial peptides, lipocalin-2, galectin-3, vaspin, fractalkine, and human neutrophil peptides in the progression of psoriasis. In addition to traditional therapies, newer therapeutics, including phosphodiesterase type 4 (PDE4) inhibitors, Janus kinase (JAK) inhibitors, monoclonal antibodies (mAbs), gene therapy, anti-T cell therapy, and phytoconstituents have been explored. In this review, we highlight nanotechnology-related developments for psoriasis treatment, including patented delivery systems and therapeutics currently in clinical trials.Item Potential herbal constituents for psoriasis treatment as protective and effective therapy(Wiley, 2020-12) Singhvi, GautamPsoriasis is a multifactorial and chronic skin disorder. It is a recurrent disease that requires incessant therapy. Psoriasis treatment includes topical and systemic routes using synthetic drugs that lead to severe unwanted adverse effects. Herbal therapy is widely used for thousands of years in countries like China and India. The use of herbal therapy in the developed region enhanced to a great extent and showed better efficacy towards psoriasis alone or as adjuvant to synthetic therapy. Herbal medicines have gained great attention in the treatment of psoriasis due to their lesser side effects compared to synthetic drugs. In this review, the various plant sources which have been found effective in psoriasis and can be used to develop novel therapeutics have been discussed. The mechanisms by which the phytoconstituents elicit anti-psoriatic activity and various research studies that have proven the effectiveness of these natural products have also been compiled in this review.Item Insight into the pivotal role of signaling pathways in psoriasis pathogenesis, potential therapeutic molecules and drug delivery approaches(Elsevier, 2023-02) Singhvi, GautamPsoriasis is a multifactorial chronic autoimmune skin disorder, the exact cause of which is still under investigation. It is classified into different types displaying various histopathological features such as hyperproliferation, irregular parakeratosis and vascular infiltration of various immune cells with neutrophils in the epidermis. Over the past few decades, psoriasis pathogenesis has been thoroughly researched, leading to several advances in the treatment using small molecules and biologics. This review focuses on describing the role of various signaling pathways, including PDE-4, JAK-STAT, S1P, A3AR and NF-κB, in psoriasis pathogenesis and associated new molecules that are either recently approved or under clinical trials. This study has also addressed the relevance of employing nanotherapeutics to boost the efficacy of psoriasis treatment.Item Preclinical safety of tetrahydrocurcumin loaded lipidic nanoparticles incorporated into tacrolimus ointment: In vitro and in vivo evaluation(Elsevier, 2022-09) Chitkara, DeepakPreclinical safety and proof of concept studies for a topical ointment comprising of concentrated tetrahydrocurcumin loaded lipidic nanoparticles (THC-LNs) and tacrolimus ointment (TTO) is proposed in the present investigation. The skin irritation potential and acute dermal toxicity were performed in rats in compliance with the Organization for Economic Cooperation and Development (OECD) guidelines (402, 404 and 410) while the cytotoxic potential was performed in HaCaT cells. Finally, in vivo evaluation was performed in Imiquimod mice model of psoriasis. In primary skin irritation assessment, TTO formulation, marketed formulation (Tacroz® Forte), THC-LNs, and blank LNs were topically applied on intact skin sites in rats while another group served as a negative control group for 72 h. TTO did not induce any adverse reactions. Repeated 28 days dermal toxicity followed by biochemical and histopathological assessment showed negligible alternations and skin lesions. THC-LNs revealed negligible cytotoxic potential in HaCaT cells. TTO showed significantly high anti-psoriatic activity in comparison to marketed ointment. This was also confirmed via histopathological evaluation. Based on these findings, it can be ascertained that TTO showed minimal toxicity and has ample potential for further clinical analysis. The above studies affirm the potential of TTO as an alternative for psoriasis.