A Novel Chitosan Nanosponge as a Vehicle for Transepidermal Drug Delivery

Transepidermal drug delivery achieves high drug concentrations at the action site and ensures continuous drug delivery and better patient compliance with fewer adverse effects. However, drug delivery through topical application is still limited in terms of drug penetration. Chitosan is a promising enhancer to overcome this constraint, as it can enhance drug diffusion by opening the tight junctions of the stratum corneum. Therefore, here, we developed a novel chitosan nanosponge (CNS) with an optimal ratio and molecular weight of chitosan to improve drug penetration through skin. To prepare the CNS, two types of chitosan (3 and 10 kDa) were each conjugated with poloxamer 407 using para-nitrophenyl chloroformate, and the products were mixed with poloxamer 407 at ratios of 5:5, 8:2, and 10:0. The resulting mixtures were molded to produce flexible soft nanosponges by simple nanoprecipitation. The CNSs were highly stable in biological buffer for four weeks and showed no toxicity in human dermal fibroblasts. The CNSs increased drug permeability through human cadaver skin in a Franz-type diffusion cell, with substantially higher permeability with 3 kDa chitosan at a ratio of 8:2. This suggests the applicability of the novel CNS as a promising carrier for efficient transepidermal drug delivery.

551 Fish Skin Compared to Cadaver Skin as a Temporary Coverage and Wound Bed Preparation for Full Thickness Burns: An Early Feasibility Trial.

Introduction Full-thickness thermal burns may require staged procedures with temporary coverage to ensure the wound bed is optimized for autografting. A potential dermal substitute for thermal injury is fish skin grafts. These are made in Iceland from freeze dried, sterilized, decellularized skin of North Atlantic cod (Gadus morhua). The gentle processing of the fish skin removes the risk of viral disease transmission to humans and retains its naturally occurring Omega3 fatty acids which are known for their pain and inflammation modulating effects. Fish skin graft has a shelf life of 3 years at room temperature, whereas cadaver skin, the current standard of care at many institutions, has to be cryopreserved, is donor derived, and contains only trace amounts of Omega3. While fish skin graft has been cleared by the FDA as a medical device for use in acute, surgical, chronic wounds, and partial thickness burns, it has not yet been indicated for use in full-thickness burns. The purpose of this clinical trial is to assess the safety and efficacy of decellularized, freeze dried fish skin as an alternative to cadaveric skin (standard of care) for temporary coverage in the setting of a full-thickness burn requiring staged grafting. Methods Patients with full thickness burns to their extremities and/or chest were randomized to have two adjacent areas (70–140 cm2 each) covered with either fish skin or cadaver skin for one week following excision. Patients then received a split thickness skin graft (STSG). Healing was observed by blinded assessors for each area weekly for three weeks, with a scarring assessment completed at 3 months post STSG. Background pain was measured by a visual analogue scale (VAS) for pain and wounds were photographed at each time point. Results Five patients are included in this initial analysis and all completed the 3-month post STSG follow up. TBSA ranged from 8–37%. The fish skin treated area was assessed to be 90% healed at the same timeframe or earlier than cadaver treated areas in all subjects. There was a trend towards a reduction in pain in the fish skin covered areas. One patient was unable to give a pain score due to heavy sedation. Adverse events were reported in all five patients, but none were associated with the use of the investigational product. Graft failures were observed in two cadaver skin covered areas and one partial failure in a fish skin covered area. Conclusions Results from this trial so far indicate that the fish skin is safe and non-inferior to cadaver skin as an early coverage for full thickness burns. Enrollment in this study is still ongoing, and patients will be followed up for 12 months.

Transdermal delivery of FITC-Dextrans with different molecular weights using radiofrequency microporation

Background Transdermal delivery is of great importance for the effective delivery of bioactive or therapeutic agents into a body. The microporation device based on radiofrequency can be used to enhance delivery efficiency by removing the epidermis layer. Methods The micropores were developed on pig skin and human cadaver skin with dermal and epidermal layers by the microporation device. The regeneration of micropores in the human cadaver skin caused by microporation was confirmed using an optical microscope and haematoxylin/eosin (H&E) staining. The permeability of fluorescein isothiocyanate-dextrans (FITC-dextrans) with different molecular weights through the pig and human cadaver skins were measured using Franz diffusion cell. Results The optical image and histological analysis confirmed that the micropores on the skin were recovered over time. The enhanced permeability through micropores was confirmed by Franz diffusion cell. The lower molecular weight of FITC-dextran permeated more on both human and pig skin. In addition, the permeation rate was higher in pig skin than in human skin. Conclusions We believe that the microporation device can be used as a potential technique for effective transdermal drug delivery.

Nanodroplet-Benzalkonium Chloride Formulation Demonstrates In Vitro and Ex-Vivo Broad-Spectrum Antiviral Activity Against SARS-CoV-2 and other Enveloped Viruses

The Covid-19 pandemic has highlighted the importance of aerosolized droplets inhaled into the nose in the transmission of respiratory viral disease. Inactivating pathogenic viruses at the nasal portal of entry may reduce viral loads, thereby reducing transmission and contagion. We have developed an oil-in-water nanoemulsion (nanodroplet) formulation containing the potent antiseptic 0.13% Benzalkonium Chloride (NE-BZK) which demonstrates safe and broad anti-viral activity. While The Centers for Disease Control and Prevention (CDC) have reported that BZK may have less reliable activity than ethyl alcohol against certain viruses, including coronaviruses, we have demonstrated that NE-BZK exhibits broad-spectrum, long-lasting antiviral activity with >99.99% in vitro killing of enveloped viruses including SARS-CoV-2, human coronavirus, RSV and influenza B. Furthermore, in vitro studies demonstrated that NE-BZK continues to kill >99.99% of human coronavirus even when diluted 20-fold, while 0.13% aqueous BZK solution (AQ-BZK) did not. Ex vivo studies of NE-BZK on human cadaver skin demonstrated persistent >99.99% killing of human coronavirus for at least 8 hours after application. AQ-BZK failed to demonstrate durable antimicrobial activity on skin over time. The repeated application of NE-BZK, twice daily for 2 weeks on to rabbit nostrils indicated safety with no irritation. These findings demonstrate that formulating BZK on the surface of proprietary nanodroplets offers a safe and effective antiviral as a significant addition to strategies to combat the spread of respiratory viral infectious diseases.

Thymoquinone-Loaded Polymeric Films and Hydrogels for Bacterial Disinfection and Wound Healing

The purpose of this study was to synthesize and characterize novel biocompatible topical polymeric film and hydrogel systems that have the potential to deliver the antibacterial agent thymoquinone (TQ) directly to the skin target site to manage the local wound infection and thereby wound healing. The polyvinyl pyrrolidone (PVP) matrix-type films containing TQ were prepared by the solvent casting method. In vitro skin permeation studies on human cadaver skin produced a mean flux of 2.3 µg TQ/cm2/h. Human keratinocyte monolayers subjected to a scratch wound (an in vitro wound healing assay) showed 85% wound closure at day 6 in the TQ group (100 ng/mL TQ) as compared to 50% in the vehicle control group (p = 0.0001). In a zone-of-inhibition (ZOI) assay, TQ-containing films and hydrogels completely wiped out Staphylococcus aureus in 10 cm diameter Tryptic Soy Agar plates while 500 µg/mL gentamicin containing filters gave 10 mm of ZOI. In an ex vivo model, TQ-containing films eradicated bacterial colonization on human cadaver skin. Furthermore, in a full-thickness wound infection model in mice, TQ-containing films showed significant activity in controlling Staphylococcus aureus infection, thereby disinfecting the skin wound. In summary, TQ-containing PVP films and hydrogels developed in this study have the potential to treat and manage wound infections.

Lipid Nanoparticles for Enhancing the Physicochemical Stability and Topical Skin Delivery of Orobol

Orobol is one of the major soy isoflavones, and has been reported to have various pharmacological activities, including an anti-skin-aging effect. However, since it has low solubility in water and physicochemical instability, the formulation of orobol for delivery into the dermal layer of the skin could be challenging. The objective of this study was to prepare lipid nanoparticles formulations of orobol to enhance its stability as well as its deposition into the skin. Formulations of orobol-loaded solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) were characterized in terms of their mean particle size, entrapment efficiency, and morphology. The nano-sized spherical NLCs formulations maintained the stability of orobol for up to 28 days. Moreover, the NLCs formulation significantly increased the in vitro deposition of orobol into both Strat-M membranes and human cadaver skin compared with the other formulations. Additionally, the NLCs formulation did not cause significant skin irritation in clinical study. These results demonstrate that a shea butter-based NLC formulation could be a promising and safe carrier system for improving the stability of orobol and enhancing its topical skin delivery.

Scalp Micro-Pigmentation via Transcutaneous Implantation of Flexible Tissue Interlocking Biodegradable Microneedles

Alopecia, characterized by hair follicle blockage and hair loss, disrupts the normal cycle of hair growth. Although not a life-threatening condition, a growing body of evidence suggests that the psychological state of individuals experiencing alopecia can be highly influenced. Despite considerable research on hair loss treatment, interest in micro-pigmentation has increased in recent decades. Micropigmentation is an effective method to camouflage the visual contrast between the scalp and hair strands. However, the localization, intensity and dimension of microdots depend highly upon the physician performing the implantation. Incorrectly localized microdots within the skin may lead to patchy or faded micropigmentation. To overcome the limitations of conventional micro-pigmentation, we aimed to develop micro-pigment-encapsulated biodegradable microneedles (PBMs), capable of accurately implanting pigments below the epithelial-dermal junction of the scalp in a minimally invasive manner. A tissue interlocking microneedle technique was utilized to fabricate double-layered PBMs over a biodegradable flexible sheet, which could be washed off post-implantation. We confirmed that the intensity, dimension and insertion depth of 1,000 μm-long PBMs was maintained on pig cadaver skin over time. This study suggested that the developed PBMs would serve as an attractive platform for scalp micro-pigmentation in the future.