Urea-Based Patches with Controlled Release for Potential Atopic Dermatitis Treatment

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Abstract

Skin diseases such as atopic dermatitis (AD) are widespread and affect people all over the world. Current treatments for dry and itchy skin are mostly focused on pharmaceutical solutions, while supportive therapies such as ointments bring immediate relief. Electrospun membranes are commonly used as a drug delivery system, as they have a high surface to volume area, resulting in high loading capacity. Within this study we present the manufacturing strategies of skin patches using polymer membranes with active substances for treating various skin problems. Here, we manufactured the skin patches using electrospun poly(vinyl butyral-co-vinyl alcohol-co-vinyl acetate) (PVB) fibers blended and electrosprayed with urea. The highest cumulative release of urea was obtained from the PVB patches manufactured via blend electrospinning with 5% of the urea incorporated in the fiber. The maximum concentration of released urea was acquired after 30 min, which was followed up by 6 h of constant release level. The simultaneous electrospinning and electrospraying limited the urea deposition and resulted in the lowest urea incorporation followed by the low release level. The urea-based patches, manufactured via blend electrospinning, exhibited a great potential as overnight treatment for various skin problems and their development can bring new trends to the textile-based therapies for AD.

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Normal keratinization in a spontaneously immortalized aneuploid human keratinocyte cell line

J. Hornung, P. Boukamp, K Markham … (1988)

In contrast to mouse epidermal cells, human skin keratinocytes are rather resistant to transformation in vitro. Immortalization has been achieved by SV40 but has resulted in cell lines with altered differentiation. We have established a spontaneously transformed human epithelial cell line from adult skin, which maintains full epidermal differentiation capacity. This HaCaT cell line is obviously immortal (greater than 140 passages), has a transformed phenotype in vitro (clonogenic on plastic and in agar) but remains nontumorigenic. Despite the altered and unlimited growth potential, HaCaT cells, similar to normal keratinocytes, reform an orderly structured and differentiated epidermal tissue when transplanted onto nude mice. Differentiation- specific keratins (Nos. 1 and 10) and other markers (involucrin and filaggrin) are expressed and regularly located. Thus, HaCaT is the first permanent epithelial cell line from adult human skin that exhibits normal differentiation and provides a promising tool for studying regulation of keratinization in human cells. On karyotyping this line is aneuploid (initially hypodiploid) with unique stable marker chromosomes indicating monoclonal origin. The identity of the HaCaT line with the tissue of origin was proven by DNA fingerprinting using hypervariable minisatellite probes. This is the first demonstration that the DNA fingerprint pattern is unaffected by long- term cultivation, transformation, and multiple chromosomal alterations, thereby offering a unique possibility for unequivocal identification of human cell lines. The characteristics of the HaCaT cell line clearly document that spontaneous transformation of human adult keratinocytes can occur in vitro and is associated with sequential chromosomal alterations, though not obligatorily linked to major defects in differentiation.

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Current strategies for sustaining drug release from electrospun nanofibers.

Shih-Feng Chou, Daniel H. Carson, Kim Woodrow (2015)

Electrospun drug-eluting fibers are emerging as a novel dosage form for multipurpose prevention against sexually transmitted infections, including HIV, and unintended pregnancy. Previous work from our lab and others show the versatility of this platform to deliver large doses of physico-chemically diverse agents. However, there is still an unmet need to develop practical fiber formulations for water-soluble small molecule drugs needed at high dosing due to intrinsic low potency or desire for sustained prevention. To date, most sustained release fibers have been restricted to the delivery of biologics or hydrophobic small molecules at low drug loading of typically <1 wt.%, which is often impractical for most clinical applications. For hydrophilic small molecule drugs, their high aqueous solubility and poor partitioning and incompatibility with insoluble polymers make long-term release even more challenging. Here we investigate several existing strategies to sustain release of hydrophilic small molecule drugs that are highly-loaded in electrospun fibers. In particular, we investigate what is known about the design constraints required to realize multi-day release from fibers fabricated from uniaxial and coaxial electrospinning.

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Composite poly(vinyl alcohol)/poly(vinyl acetate) electrospun nanofibrous mats as a novel wound dressing matrix for controlled release of drugs

Marziyeh Jannesari, Jaleh Varshosaz, Mohammad Morshed … (2011)

The aim of this study was to develop novel biomedicated nanofiber electrospun mats for controlled drug release, especially drug release directly to an injury site to accelerate wound healing. Nanofibers of poly(vinyl alcohol) (PVA), poly(vinyl acetate) (PVAc), and a 50:50 composite blend, loaded with ciprofloxacin HCl (CipHCl), were successfully prepared by an electrospinning technique for the first time. The morphology and average diameter of the electrospun nanofibers were investigated by scanning electron microscopy. X-ray diffraction studies indicated an amorphous distribution of the drug inside the nanofiber blend. Introducing the drug into polymeric solutions significantly decreased solution viscosities as well as nanofiber diameter. In vitro drug release evaluations showed that both the kind of polymer and the amount of drug loaded greatly affected the degree of swelling, weight loss, and initial burst and rate of drug release. Blending PVA and PVAc exhibited a useful and convenient method for electrospinning in order to control the rate and period of drug release in wound healing applications. Also, the thickness of the blend nanofiber mats strongly influenced the initial release and rate of drug release.