Biology subjects

keshari, R.

Publications and source records attributed to keshari, R..

3 recordsLinked to original sources

bioRxiv2025

PLGA Soya Lecithin Based Hybrid Nanocomposite for Targeted Topical Delivery of Resveratrol in Psoriasis Management

Psoriasis is a recurring autoimmune-driven inflammatory skin disorder characterised by red, scaly, dry skin patches, keratinocyte hyperproliferation and infiltration of inflammatory cells, impacting millions globally. Patients with psoriasis often require repeated treatments with corticosteroids, which are often associated with significant side effects and comorbidities. Therefore, there is a growing need for advanced nanomedicine-based therapeutic approaches. Resveratrol (RSV), a plant-derived polyphenol, has shown promising anti-inflammatory and antioxidant properties for the treatment and management of psoriasis. However, its therapeutic potential is limited due to its poor solubility, low stability, and reduced skin penetration. To overcome these challenges, we have developed dual-carrier conjugated nanoparticles (RSVNPL) composed of soya lecithin and poly(lactic-co-glycolic acid) (PLGA). To further enhance its ease of application and prolong skin residence time, RSVNPL was incorporated into a carbomer 974P-based hydrogel system, forming RSVNPGel. Our formulation demonstrated improved physicochemical properties, including enhanced spreadability, superior skin adhesiveness and stability. Ex vivo skin permeation studies confirmed a significantly higher accumulation of RSV in the epidermis and dermis compared to free drugs. In vivo, efficacy was investigated using imiquimod (IMQ)-induced psoriatic mouse model, where RSVNPGel treatment led to a notable reduction in epidermal thickness, inflammatory cell infiltration, and key histopathological features associated with psoriasis. Additionally, serum biochemical analysis and organ histology established the biocompatibility and safety of the formulation. Overall, RSVNPGel presents a promising nanocarrier-based strategy for the effective topical management of psoriasis, enhancing RSV delivery and therapeutic efficacy while minimizing systemic exposure. Research HighlightsO_LIHybrid nanoparticles composite of soya lecithin and PLGA were developed for RSV delivery. C_LIO_LIThe formulation enhanced skin penetration, retention and created a better skin adhesive profile in psoriatic lesions. C_LIO_LISignificant anti-psoriatic effects were achieved in a preclinical model. C_LIO_LIThe system showed excellent safety and biocompatibility. C_LI Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/648585v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@e28c4corg.highwire.dtl.DTLVardef@1690c80org.highwire.dtl.DTLVardef@1b3e4bforg.highwire.dtl.DTLVardef@16ec0ad_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2024

Eugenol loaded lipid nanoparticles derived hydrogels ameliorate psoriasis-like skin lesions by lowering oxidative stress and modulating inflammation

Psoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, keratinocyte over-proliferation, 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 presenting hydrogels loaded with Eugenol (EU) in combination with Carbopol 974P (EUNPGel) for potential psoriasis management. EUN-loaded lipid nanoparticles (EUNPs) exhibit superior drug loading, enhanced release kinetics, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs have been shown to inhibit keratinocyte proliferation, induce apoptosis, and augment the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions has demonstrated effective dermal penetration, suppressing keratinocyte hyperplasia and restoring epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3. 75 to 0. 5 within five days. These findings highlight the potential of EUNPGel as an innovative nanomedicine for treating inflammation. 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. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/599274v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@1f12fe6org.highwire.dtl.DTLVardef@17fa70forg.highwire.dtl.DTLVardef@1b0f28forg.highwire.dtl.DTLVardef@4ae07_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIHydrogel loaded with eugenol is an innovative alternative for psoriasis management. C_LIO_LISuperior drug loading, release kinetics, stability, and ROS scavenging capacity. C_LIO_LICurb (human keratinocyte) HaCaT cells proliferation, induce apoptosis, lower IL-6 mediated inflammation. C_LIO_LIEffective dermal penetration and retention both in vivo and ex vivo. C_LI

immunology↗

bioRxiv2024

Transcutaneous delivery of disease specific PI3K/Akt/mTOR inhibitor based hybrid nanoparticles in hydrogel system for the management of psoriasis: Insights from in vivo studies

We have reported robust and scalable lipid polymeric conjugated hybrid nanoparticles comprised of phospholipid shell and polymeric core that combine the benefit of both polymeric and lipid nanoparticles. Rapamycin, a PI3K/Akt/mTORC1 inhibitor, was encapsulated inside the lipid-polymeric conjugated spherical-shaped hybrid nanoparticles (RPMN), having an encapsulation efficiency of {approx} 83% and particle size {approx} 277.6 nm. Further, RPMN was converted into the carpool-based hydrogel system (RPMNGel), which enhanced release kinetics, long-term stability and skin residence time. Specifically, in an in-vivo imiquimod-induced psoriatic model, RPMNGel showed high accumulation and deeper penetration inside the epidermis, slowly diffusing away inside the psoriatic skin without causing any side effect to normal skin. This leads to longer and sustained retention over more than three days without being affected by sweat, humidity or wiping due to adherence between the stratum corneum and epidermis. Similarly, the cumulative PASI score was also reduced from 10.25 to 1.75 on day 7 in the group treated with RPMNGel. Overall, RPMNGel has a potential role in treating and managing psoriasis. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/599287v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1366d88org.highwire.dtl.DTLVardef@51255forg.highwire.dtl.DTLVardef@16ca71dorg.highwire.dtl.DTLVardef@4f93e9_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗