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.

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.

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.

Effect of iron and silica nanoparticles’ size on in vitro human skin binding and penetration

This in vitro skin study determined absorption, diffusion, and binding rates of four [14C]-labeled nanoparticles (NPs): 12 nm Fe3O4, 32 nm Fe3O4@SiO2, 33 nm SiO2, and 78 nm SiO2 in each layer of human cadaver skin. In vitro microdialysis device and flow-through skin diffusion system were used to measure the binding affinity to the stratum corneum (SC) and permeability into/through skin layer of the four NPs with different physical–chemical properties, respectively, in short (30 min) and/or long (24 hours) exposures. Results show that NP size is an important factor affecting NP percutaneous absorption. The 12 nm Fe3O4 NPs reached the SC and viable epidermis; 32 nm Fe3O4@SiO2 core/shell NPs only reached SC. However, 33 nm and 78 nm silica NPs did not permeate SC. Similar patterns were observed for NP binding affinity to SC and dermatopharmacokinetic analysis using the tape stripping method. The binding affinity determination may be a useful method to efficiently screen skin penetration of NPs.