Recombinant neutralizing secretory IgA antibodies for preventing mucosal acquisition and transmission of SARS-CoV-2.

Passive delivery of antibodies to mucosal sites may be a valuable adjunct to COVID-19 vaccination to prevent infection, treat viral carriage, or block transmission. Neutralizing monoclonal IgG antibodies are already approved for systemic delivery, and several clinical trials have been reported for delivery to mucosal sites where SARS-CoV-2 resides and replicates in early infection. However, secretory IgA may be preferred because the polymeric complex is adapted for the harsh, unstable external mucosal environment. Here, we investigated the feasibility of producing neutralizing monoclonal IgA antibodies against SARS-CoV-2. We engineered two class-switched mAbs that express well as monomeric and secretory IgA (SIgA) variants with high antigen-binding affinities and increased stability in mucosal secretions compared to their IgG counterparts. SIgAs had stronger virus neutralization activities than IgG mAbs and were protective against SARS-CoV-2 infection in an in vivo murine model. Furthermore, SIgA1 can be aerosolized for topical delivery using a mesh nebulizer. Our findings provide a persuasive case for developing recombinant SIgAs for mucosal application as a new tool in the fight against COVID-19.

Examination of the Rate and Extent of Drug Released from Commercial Topical Delivery Systems During Wear: An Example with Lidocaine Topical Systems.

OBJECTIVE: This study aimed to determine the extent and rate of lidocaine released in vivo from two bioequivalent topical delivery systems (TDS) by using complementary assessments: pharmacokinetic analysis in healthy human volunteers, and residual lidocaine in TDS following 12 h of wear. The goal was to explore a potentially more clinically meaningful strength presentation than percent active pharmaceutical ingredient loaded in topical systems. METHODS: A three-arm, open-label, crossover clinical study was conducted in 23 human subjects, with 5% lidocaine topical systems from two manufacturers, and intravenous lidocaine administration. Residual drug and LC-MS/MS analyses were performed on worn TDS and serum samples. The rate and extent of drug released from the TDS during wear were determined through (1) calculations of consumed lidocaine via analysis of residual drug in worn TDS, and (2) a pharmacokinetic approach via derivation of the absolute clearance and serum lidocaine concentration at steady state. RESULTS: Overall the pharmacokinetic approach underestimated the amount transferred to the subject and exhibited greater variability, which may relate to natural inter-subject variability in pharmacokinetic parameters. Further, lidocaine TDS are intended for localized, not systemic, delivery and this may also explain some of the variability seen in the systemic serum concentrations. CONCLUSIONS: The residual drug and pharmacokinetic approaches align well for transdermal formulations, but the differences in administration route (topical versus transdermal) all but eliminates the potential use of the pharmacokinetic approach unless additional compartmental modeling is explored.

Dendritic Oligoethylenimine Decorated Liposome with Augmented Corneal Retention and Permeation for Efficient Topical Delivery of Antiglaucoma Drugs.

The topically administered glaucoma medications usually encounter serious precorneal drug loss and low corneal penetration, leading to a low bioavailability. In addition, due to the complexity of glaucoma etiology, a single medication is often insufficient. In this work, we report a novel dendritic oligoethylenimine decorated liposome for codelivery of two antiglaucoma drugs, latanoprost and timolol. The liposome showed a uniform nanoscopic particle size, positive surface charge, and excellent dual-drug loading capacity. A prolonged precorneal retention is observed by using this liposomal delivery system. This liposomal delivery system presents increased cellular uptake and tight junctions opening capacity, contributing respectively to the transcellular and paracellular permeation, thereby enhancing the trans-corneal transportation. Following topical administration of one eye drop in brown Norway rats, the dual-drug-loaded liposome formulation resulted in a sustained and effective intraocular pressure reduction as long as 5 days, without inducing ocular inflammation, discomfort, and tissue damage.

Formulation characterization of lecithin organogel as topical drug delivery system for psoriasis: In-vitro permeation and preclinical evaluation.

Psoriasis is a chronic inflammatory and proliferative skin disease that causes pathological skin changes and has a substantial impact on the quality of patient life. Apremilast was approved by the US Food and Drug Administration as an oral medication for psoriasis and is beneficial in mild to moderate conditions for chronic usage. However, 5%-7% of withdrawals were reported due to severe side effects. To address the issue, a localized drug delivery strategy via the topical route may be a viable approach. However, poor physicochemical properties make it vulnerable to passing through the skin, requiring a specialized drug delivery system to demonstrate its full potential via a topical route like lecithin organogel. The formulation was optimized by screening the suitable lecithin type and non-polar solvents based on the gel formation ability of lecithin and the solubility of apremilast in the solvent. The pseudo-ternary diagram was used to optimize the water content required to form the gel. The optimized gel was found to be shear thinning characterized for rheological parameters, in-vitro diffusion studies, and in-vitro skin distribution studies. Preclinical studies in Imiquimod-induced mice showed a better reduction in severity index, cytokine levels, and epidermal hyperplasia from the lecithin organogel group compared to the apremilast oral administration and marketed standard topical gel group. Based on these results, lecithin organogel can be considered a promising approach to deliver molecules like apremilast by topical route in psoriatic-like conditions.

Silica Microparticles from Sugarcane By-Products as an Encapsulation System for Retinoids Aimed at Topical Sustained Release.

The encapsulation of retinol within silica microparticles has emerged as a promising opportunity in the realm of cosmetic and pharmaceutical formulations, driven by the need to reinforce the photoprotection and oxidation stability of retinol. This work examines the process of encapsulating retinol into silica microparticles. The association efficiency, microparticle size, molecular structure, morphology, oxidation, and release profile, as well as biocompatibility and skin sensitization, were evaluated. Results showed that 0.03% of retinol and 9% of emulsifier leads to an association efficiency higher than 99% and a particle size with an average of 5.2 µm. FTIR results indicate that there is an association of retinol with the silica microparticles, and some may be on the surface. Microscopy indicates that when association happens, there is less aggregation of the particles. Oxidation occurs in two different phases, the first related to the retinol on the surface and the second to the associated retinol. In addition, a burst release of up to 3 h (30% free retinol, 17% associated retinol) was observed, as well as a sustained release of 44% of retinol up to 24 h. Encapsulation allowed an increase in the minimal skin cytotoxic concentrations of retinol from 0.04 µg/mL to 1.25 mg/mL without skin sensitization. Overall, retinol is protected when associated with silica microparticles, being safe to use in cosmetics and dermatology.

Antipsoriatic Effect of Silymarin NLCs Based Gel: In Vitro and In Vivo Activity.

Psoriasis is a chronic inflammatory disorder affecting over 100 million people, requires long-term therapy. Current treatments offer only symptomatic relief. However, phytoconstituents-based therapies like Silymarin (SLM) have shown promising effects. The study aims to develop, optimize, and evaluate a novel stable SLM NLC gel to improve anti-psoriatic activity by enhancing its permeability and retention into the dermal layer. SLM NLC formulation was prepared and optimized using 32 full factorial designs. The formulation was evaluated for the particle size, PDI, zeta potential, and % entrapment efficiency, evaluated by Transmission electron microscopy and thermal analysis. The freeze dried and prepared NLC-loaded gel was evaluated for physicochemical parameters, ex-vivo, and in-vivo studies. SLM-loaded NLC shows 624 nm particle size, 0.41 PDI, 92.95% entrapment efficiency, and -31.6 mV zeta potential. The sphere form of NLCs was confirmed using TEM. Controlled drug release was observed in ex vivo studies, low PASI score compared to disease control. Further, the levels of IL-6, TNF-α, and NF-κB were also reduced. The results are supported by histopathology showing minimal parakeratosis indicated in the SLM NLC-treated group. Prepared NLC-based shows enhance topical penetration and decrease the thickness of psoriatic plaques in the in vivo study.

Nanofiber-based Delivery of Luliconazole: Fabrication, Characterization, and Therapeutic Performance Assessment.

This study introduces and assesses the potential of a Luliconazole-loaded nanofiber (LUL-NF) patch, fabricated through electrospinning, for enhancing topical drug delivery. The primary objectives involve evaluating the nanofiber structure, characterizing physical properties, determining drug loading and release kinetics, assessing antifungal efficacy, and establishing the long-term stability of the NF patch. LUL-NF patches were fabricated via electrospinning and observed by SEM at approximately 200 nm dimensions. The comprehensive analysis included physical properties (thickness, folding endurance, swelling ratio, weight, moisture content, and drug loading) and UV analysis for drug quantification. In vitro studies explored sustained drug release kinetics, while microbiological assays evaluated antifungal efficacy against Candida albicans and Aspergillus Niger. Stability studies confirmed long-term viability. Comparative analysis with the pure drug, placebo NF patch, LUL-NF patch, and Lulifod gel was conducted using agar diffusion, revealing enhanced performance of the LUL-NF patch. SEM analysis revealed well-defined LUL-NF patches (0.80 mm thickness) with exceptional folding endurance (> 200 folds) and a favorable swelling ratio (12.66 ± 0.73%). The patches exhibited low moisture uptake (3.4 ± 0.09%) and a moisture content of 11.78 ± 0.54%. Drug loading in 1 cm2 section was 1.904 ± 0.086 mg, showing uniform distribution and sustained release kinetics in vitro. The LUL-NF patch demonstrated potent antifungal activity. Stability studies affirmed long-term stability, and comparative analysis highlighted increased inhibition compared to a pure drug, LUL-NF patch, and a commercial gel. The electrospun LUL-NF patch enhances topical drug delivery, promising extended therapy through single-release, one-time application, and innovative drug delivery strategies, supported by thorough analysis.

Revolutionizing Knee Osteoarthritis Treatment: Innovative Self-Nano-Emulsifying Polyethylene Glycol Organogel of Curcumin for Effective Topical Delivery.

In the current study, self-nano-emulsifying (SNE) physically cross-linked polyethylene glycol (PEG) organogel (SNE-POG) as an innovative hybrid system was fabricated for topical delivery of water-insoluble and unstable bioactive compound curcumin (CUR). Response surface methodology (RSM) based on Optimal Design was utilized to evaluate the formulation factors. Solid fiber mechanism with homogenization was used to prepare formulations. Pharmaceutical evaluation including rheological and texture analysis, their mathematical correlations besides physical and chemical stability experiments, DSC study, in vitro release, skin permeation behavior, and clinical evaluation were carried out to characterize and optimize the SNE-OGs. PEG 4000 as the main organogelator, Poloxamer 188 (Plx188) and Ethyl Cellulose (EC) as co-gelator/nanoemulsifier agents, and PEG 400 and glycerin as solvent/co-emulsifier agents could generate SNE-POGs in PS range of 356 to 1410 nm that indicated organic base percentage and PEG 4000 were the most detrimental variables. The optimized OG maintained CUR stable in room and accelerated temperatures and could release CUR sustainably up to 72 h achieving high flux of CUR through guinea pig skin. A double-blind clinical trial confirmed that pain scores, stiffness, and difficulty with physical function were remarkably diminished at the end of 8 weeks compared to the placebo (71.68% vs. 7.03%, 62.40% vs. 21.44%, and 45.54% vs. 8.66%, respectively) indicating very high efficiency of system for treating knee osteoarthritis. SNE-POGs show great potential as a new topical drug delivery system for water-insoluble and unstable drugs like CUR that could offer a safe and effective alternative to conventional topical drug delivery system.

Drug permeation enhancement, efficacy, and safety assessment of azelaic acid loaded SNEDDS hydrogel to overcome the treatment barriers of atopic dermatitis.

Atopic dermatitis is one of the most widespread chronic inflammatory skin conditions that can occur at any age, though the prevalence is highest in children. The purpose of the current study was to prepare and optimize the azelaic acid (AzA) loaded SNEDDS using Pseudo ternary phase diagram, which was subsequently incorporated into the Carbopol 940 hydrogel for the treatment of atopic dermatitis. The composition was evaluated for size, entrapment efficiency, in vitro, ex vivo, and in vivo studies. The polydispersity index of the optimized preparation was found to be less than 0.5, and the size of the distributed globules was found to be 151.20 ± 3.67 nm. The SNEDDS hydrogel was characterized for pH, viscosity, spreadability, and texture analysis. When compared to the marketed formulation, SNEDDS hydrogel was found to have a higher rate of permeation through the rat skin. In addition, a skin irritation test carried out on experimental animals showed that the SNEDDS formulation did not exhibit any erythematous symptoms after a 24-h exposure. In conclusion, the topical delivery of AzA through the skin using SNEDDS hydrogel could prove to be an effective approach for the treatment of atopic dermatitis.

Self-assembled Gallic acid loaded lecithin-chitosan hybrid nanostructured gel as a potential tool against imiquimod-induced psoriasis.

Increased thickness of the skin and hyperproliferation of keratinocyte cell is the main obstacle in the treatment of psoriasis. Gallic Acid (GA) has shown efficacious results against the hyperproliferation of keratinocytes while lipid-polymer loaded hybrid nanoparticles (LPHNs) have an edge over lipidic and polymeric nanoparticles considering drug loading, controlled release, stability, and retention. The LPHNs were optimized using Box-Behnken method and was further characterized by FTIR, DSC and Zetasizer. The optimized preparation demonstrated a size of 170.5 ± 0.087 nm and a PDI of 0.19 ± 0.0015, respectively. The confocal study has suggested that the hybrid nanosystem enhanced the drug penetration into the deeper layer with a higher drug release of 79 ± 0.001% as compared to the gallic acid-loaded gel. In addition, the formulation significantly reduced PASI score and splenomegaly without causing any serious irritation. The morphological study of the spleen suggested that the prepared formulation has well controlled the disease compared to the marketed formulation while maintaining a normal level of immune cells after treatment. Hence GALPHN could be accepted as one of the excellent vehicles for the topical conveyance of GA (gallic acid) due to enhanced penetration, and good retention, along with fewer side effects and higher efficacy of the GALPHN gel against imiquimod (IMQ) induced psoriasis.

Debulking SARS-CoV-2 in saliva using angiotensin converting enzyme 2 in chewing gum to decrease oral virus transmission and infection.

To advance a novel concept of debulking virus in the oral cavity, the primary site of viral replication, virus-trapping proteins CTB-ACE2 were expressed in chloroplasts and clinical-grade plant material was developed to meet FDA requirements. Chewing gum (2 g) containing plant cells expressed CTB-ACE2 up to 17.2 mg ACE2/g dry weight (11.7% leaf protein), have physical characteristics and taste/flavor like conventional gums, and no protein was lost during gum compression. CTB-ACE2 gum efficiently (>95%) inhibited entry of lentivirus spike or VSV-spike pseudovirus into Vero/CHO cells when quantified by luciferase or red fluorescence. Incubation of CTB-ACE2 microparticles reduced SARS-CoV-2 virus count in COVID-19 swab/saliva samples by >95% when evaluated by microbubbles (femtomolar concentration) or qPCR, demonstrating both virus trapping and blocking of cellular entry. COVID-19 saliva samples showed low or undetectable ACE2 activity when compared with healthy individuals (2,582 versus 50,126 ΔRFU; 27 versus 225 enzyme units), confirming greater susceptibility of infected patients for viral entry. CTB-ACE2 activity was completely inhibited by pre-incubation with SARS-CoV-2 receptor-binding domain, offering an explanation for reduced saliva ACE2 activity among COVID-19 patients. Chewing gum with virus-trapping proteins offers a general affordable strategy to protect patients from most oral virus re-infections through debulking or minimizing transmission to others.

Spray coverage analysis of topical sprays formed by cold thermoreversible hydrogels.

OBJECTIVE: Sprayable hydrogel formulations are promising topical treatments for skin wounds due to their ability to reduce application pain, prolong drug release, and provide moisture to promote skin healing. These viscoelastic materials, however, present challenges in spray ability which can be overcome using a thermoreversible hydrogels sprayed as lower viscosity liquids at cooler temperatures. The purpose of this research was to evaluate the impact of thermoreversible hydrogel formulation and device characteristics on topical spray patterns and to develop metrics to accurately describe surface coverage. METHODS: Cold solutions of Pluronic F127 were prepared at 15, 17, and 20% (w/w) and tested to determine their rheological properties. Formulations were sprayed from hand-held atomizing pump dispersers under cold conditions and two distinct areas of their spray patterns analyzed: the concentrated core and the full spray pattern. Traditional analysis of spray patterns was conducted to determine major and minor axes, ovality, and total area. In addition, new scripts were developed to evaluate the concentrated core. RESULTS: The full spray pattern analysis quantified the total area over which the spray would extend a flat surface, while the concentrated core analysis quantified the continuous region where a drug dose would be concentrated. The combination of formulation viscosity, sprayer nozzle, and spray distance produced spray patterns from highly concentrated to highly dispersed. These parameters can be controlled to generate desired hydrogel spray patterns for application on skin surfaces. CONCLUSION: The developed metrics provide a basis for topical spray analysis that can inform future product performance.

Design and fabrication of Sesamol-loaded transfersomal gel for wound healing: physicochemical characterization and in-vivo evaluation.

OBJECTIVE: In the present study, an attempt has been made to develop SL-loaded transfersomal gel for the effective treatment of delayed wound healing. SIGNIFICANCE: The wound healing process consists of a complex series of biochemical events and changes in cellular activity that restore the integrity of the skin and the subcutaneous tissue. Sesamol (SL), which is a natural phenolic compound, is known for its antioxidant properties, anti-inflammatory properties, and wound-healing abilities. METHODS: A thin-film hydration method was used to prepare SL-loaded transfersomes. Different formulations containing Tween-80 and Span-80 as edge activators were prepared and optimized. Various characteristics of vesicles were assessed, such as size, shape, loading efficiency, deformability, and in vitro skin penetration. The optimized formulation was then incorporated into 1% carbopol 940 gel. An in vivo wound healing potential of the selected formulation was assessed by an excision wound model. RESULTS: The SL-loaded transfersomal gel displayed improved skin penetration and better skin deposition. Wound healing studies showed that the highest wound contraction was observed with SL-loaded transfersomes. Following 21 days of application of the transfersomal gel, a marked improvement in skin histological architecture was found. CONCLUSION: The study findings suggest that transfersomal gel has great potential as a therapeutic option in wound healing.

Co-Encapsulation of Drugs for Topical Application-A Review.

Achieving the best possible outcome for the therapy is the main goal of a medicine. Therefore, nanocarriers and co-delivery strategies were invented to meet this need, as they can benefit many diseases. This approach was applied specifically for cancer treatment, with some success. However, these strategies may benefit many other clinical issues. Skin is the largest and most exposed organ of the human body, with physiological and psychological properties. Due to its exposition and importance, it is not difficult to understand how many skin diseases may impact on patients' lives, representing an important burden for society. Thus, this review aims to summarize the state of the art in research concerning nanocarriers and co-delivery strategies for topical agents' applications targeting skin diseases. The challenge for the medicine of the future is to deliver the drug with spatial and temporal control. Therefore, the co-encapsulation of drugs and the appropriate form of administration for them are so important and remain as unmet needs.

Plaster Gel Loaded with Silver Nanoparticle-Mediated Ganoderma applanatum: from Fabrication to Evaluation.

Traditional Asian remedies have mainly employed the macrofungus Ganoderma applanatum, which belongs to the family Ganodermataceae, as a medicinal mushroom due to its high antibacterial and antioxidant activity. Extracts of the fungus can be synthesized into nanoparticles, which are subsequently produced as plaster gels. Synthesized silver nanoparticle-mediated G. applanatum was discovered to have the greatest ability to inhibit bacterial growth in S. epidermidis. When applied to the skin, the prepared plaster gel converted from a gel to a film; thus, both gel and film generation are characteristic of its formulation. The plaster gel that was made was found to be consistent and attractive, and the yellow color had darkened. Its viscosity and pH were appropriate for the application and allowed it to remain on the skin without dripping or reacting with the skin until it dried. A shorter duration for film formation is possible. The film's tensile was slightly reduced, and it exhibited excellent thermal stability. Decomposition of the generated film occurred at a slower rate, which constrained the polymer chain's ability to move. The semi-crystalline structure was characteristic of the film. It was found that particles were distributed in the film. Rapid release from plaster gel within 4 h was seen, and this was followed by a period of a slowly declining release rate over 12 h. The accurate first-order kinetic used to estimate the release rate of the formulation. The plaster gel demonstrated greater antibacterial activity than the MIC value indicated. The in vivo evaluation was positive and showed no skin irritation. The formulation showed good stability. Therefore, this indicated that the prepared plaster gel is appropriate for topical pharmaceutical delivery and safe for skin application.

Understanding Formulation and Temperature Effects on Dermal Transport Kinetics by IVPT and Multiphysics Simulation.

PURPOSE: It is often unclear how complex topical product formulation factors influence the transport kinetics through skin tissue layers, because of multiple confounding attributes. Environmental factors such as temperature effect are also poorly understood. In vitro permeation testing (IVPT) is frequently used to evaluate drug absorption across skin, but the flux results from these studies are from a combination of mechanistic processes. METHOD: Two different commercially available formulations of oxybenzone-containing sunscreen cream and continuous spray were evaluated by IVPT in human skin. Temperature influence between typical skin surface temperature (32°C) and an elevated 37°C was also assessed. Furthermore, a multiphysics-based simulation model was developed and utilized to compute the flux of modeled formulations. RESULTS: Drug transport kinetics differed significantly between the two drug products. Flux was greatly influenced by the environmental temperature. The multiphysical simulation results could reproduce the experimental observations. The computation further indicated that the drug diffusion coefficient plays a dominant role in drug transport kinetics, influenced by the water content which is also affected by temperature. CONCLUSION: The in vitro testing and bottom-up simulation shed insight into the mechanism of dermal absorption kinetics from dissimilar topical products.

Hydrogels for localized drug delivery: A special emphasis on dermatologic applications.

Skin disease treatment is a complex and time-consuming process due to the complex etiology, numerous side effects of conventional therapies, and difficulties in determining primary causes of the disease. Superficial wounds are often easy to treat. However, treatment of severe wounds caused by burn is challenging for clinicians. Optimum therapeutic benefits are based on the site-specific delivery of medicaments at the right time for a prolonged duration. Systemic toxicity and frequent dosing are the major challenges associated with the use of conventional therapeutics. Hydrogels are material of choice for drug delivery because of their high biocompatibility and ability to hold and release therapeutic agents. The number of hydrogels available for use in cosmetology and dermatology continues to grow during the past 1-2 decades. However, new hydrogel materials with high biocompatibility, antibacterial properties, and the ability to stimulate skin regeneration processes are in high demand. These are three-dimensional networks, which absorb a large amount of biological fluids and water. Hydrogels can be used as a biosensor, carrier systems for cells, drug delivery carriers especially for topical applications and in contact lenses. Hydrogels are highly porous carriers containing about 90% water. Stimuli-responsive hydrogels cause a change in network structure that is completely reversible in nature. The present review describes the applications of hydrogels in pharmaceutical formulations with a special emphasis on the treatment of dermatologic conditions such as acne, psoriasis, and mycosis.

Topical delivery of PD-1 inhibitors with laser-assisted passive diffusion and active intradermal injection: Investigation of cutaneous pharmacokinetics and biodistribution patterns.

BACKGROUND AND OBJECTIVES: Current cancer immunotherapeutic treatment with PD-1 inhibitors is administered systemically. However, a local treatment strategy may be advantageous as it could provide targeted drug delivery as well as attenuate side effects seen with systemic treatments. For keratinocyte cancers, where surgical excision is not always applicable, an alternate local treatment approach would be beneficial. This study aims to examine cutaneous pharmacokinetics and biodistribution of the PD-1 inhibitor nivolumab, locally delivered either by ablative fractional laser (AFL)-assisted passive diffusion or active intradermal injection, in vivo. MATERIALS AND METHODS: In vivo pig skin was either exposed to CO2 AFL (80 mJ/mb by two stacked pulses of 40 mJ/mb) at 5% or 15% density followed by topical application of nivolumab (1 mg/ml, 100 µl/10 × 10 mm) or intradermally injected with nivolumab (1 mg/ml, 100 µl). Cutaneous nivolumab delivery was evaluated at different timepoints (0, 1, 2, 4 hours and 2 days) at two tissue depths (100-800 and 900-1600 µm) by ELISA. Visualization of cutaneous biodistribution was shown in vertical tissue sections using HiLyte FluorTM 488 SE labeled nivolumab for fluorescence microscopy whereas nivolumab was DOTA-tagged with Dysprosium before the laser ablation-inductively coupled plasma-mass spectrometry analysis (LA-ICP-MS). RESULTS: Our in vivo study revealed different pharmacokinetic and biodistribution patterns for the AFL- and injection techniques. A superficial horizontal band-like uptake of nivolumab was provided with AFL-assisted passive diffusion whereas a deep focal deposition was seen with active intradermal injection, compared with controls showing remnant deposition on the skin surface. AFL-assisted nivolumab uptake in upper dermis peaked after 4 hours (p < 0.01). The cutaneous concentration of nivolumab achieved by intradermal injection was markedly higher than with AFL, the highest deposition with intradermal injection was detected at time 0 hours in both upper and deep dermis (p < 0.01) and decreased throughout the study period, although the concentration remained higher compared with saline control injections at all time points (0 hours -2 d) (p < 0.01). CONCLUSION: Local cutaneous delivery of nivolumab with either AFL or intradermal injection revealed two different pharmacokinetic and biodistribution patterns. Passive AFL-assisted diffusion of nivolumab resulted in enhanced uptake after 4 hours, while intradermal actively injected nivolumab showed immediate enhanced cutaneous deposition with retention up to 2 days after injection. The two local delivery techniques show potential for development of individualized treatment strategies depending on the clinical tumor appearance.

Diversifying the skin cancer-fighting worthwhile frontiers: How relevant are the itraconazole/ascorbyl palmitate nanovectors?

Fighting malignant neoplasms via repurposing existing drugs could be a welcome move for prosperous cancer remediations. In the current work, nanovehiculation and optimization of the repositioned itraconazole (ITZ) utilizing ascorbyl palmitate (AP) aspasomes would be an auspicious approach. Further, the optimized aspasomes were incorporated in a cream and tracked for skin deposition. The in vivo efficacy of aspasomal cream on mice subcutaneous Ehrlich carcinoma model was also assessed. The optimized aspasomes revealed nano size (67.83 ± 6.16 nm), negative charge (-79.40 ± 2.23 mV), > 95% ITZ entrapment and high colloidal stability. AP yielded substantial antioxidant capacity and pushed the ITZ cytotoxicity forward against A431 cells (IC50 = 5.3±0.27 µg/mL). An appealing privilege was the aspasomal cream that corroborated spreadability, contemplated skin permeation and potentiated in vivo anticancer competence, reflected in 62.68% reduction in the tumor weight. Such synergistic tumor probes set the foundation for futuristic clinical translation and commercialization.

Photochemoprevention of ultraviolet Beam Radiation-induced DNA damage in keratinocytes by topical delivery of nanoformulated Epigallocatechin-3-gallate.

Ultraviolet Beam (UVB) radiation is the main cause of skin cancer worldwide. Besides biocompatibility, the instability and limited skin permeability are the most challenging features of many effective photochemopreventive agents. (-)-Epigallocatechin-3-gallate (EGCG) is a natural polyphenolic compound extracted from Camellia sinensis that has been demonstrated to have antioxidant, anti-inflammatory, and anti-cancer properties. We evaluated the efficacy of three innovative EGCG nanoformulations in chemoprevention of UVB-induced DNA damage in keratinocytes. Results indicated that the EGCG nanoformulations reduced UVB-induced oxidative stress elevation and DNA damage. The nanoformulations also reduced the UVB-induced formation of pyrimidine and pyrimidone photoproducts in 2D human immortalized HaCaT keratinocytes and SKH-1 hairless mice through antioxidant effects and possibly through absorption of UVB radiation. In addition, EGCG nanoformulations inhibited UVB-induced chemokine/cytokine activation and promoted EGCG skin permeability and stability. Taken together, the results suggest the use of EGCG nanoformulations as potential natural chemopreventive agents during exposure to UVB radiation.