Corticosteroid-loaded chitosan-based in-situ forming gel combined with microneedle technology for improvement of burn eschar wound healing.

Burn is one of the most common skin injuries and accounts for 300,000 deaths annually. Debridement and antibiotic therapy are major burn treatments, however, as debridement is not always possible and many drugs have poor penetration into necrotic tissue, permeation enhancement is acquired. Another challenge is the short duration of topically applied drugs. This study aims to address both problems by combining in-situ forming gels and microneedles. A chitosan-based in-situ forming gel of hydrocortisone was applied to human burn eschar using microneedles. The formulation was optimized using Design-Expert software. Formulation characterization was done in terms of gelling time and temperature, thermal analysis, release phenomenon, rheology, texture analysis, and stability. Finally, animal studies on mice burn wound treatment were conducted. Results showed that optimized formulation controlled the drug release, and wherever microneedle was used, drug permeation and flux increased (P-value < 0.05). In all ex-vivo and in-vivo stages, gel plus microneedle (length of 1.5 mm and application mode of 2) produced the best results concerning increased flux and faster recovery of burn eschar. In conclusion, the in-situ forming gel with appropriate texture, quality, and stability in combination with microneedle can be a good candidate for the controlled release of drugs in third-degree burn eschars.

Protein-based microneedles for biomedical applications: A systematic review.

Microneedles are minimally-invasive devices with the unique capability of bypassing physiological barriers. Hence, they are widely used for different applications from drug/vaccine delivery to diagnosis and cosmetic fields. Recently, natural biopolymers (particularly carbohydrates and proteins) have garnered attention as safe and biocompatible materials with tailorable features for microneedle construction. Several review articles have dealt with carbohydrate-based microneedles. This review aims to highlight the less-noticed role of proteins through a systematic search strategy based on the PRISMA guideline from international databases of PubMed, Science Direct, Scopus, and Google Scholar. Original English articles with the keyword "microneedle(s)" in their titles along with at least one of the keywords "biopolymers, silk, gelatin, collagen, zein, keratin, fish-scale, mussel, and suckerin" were collected and those in which the proteins undertook a structural role were screened. Then, we focused on the structures and applications of protein-based microneedles. Also, the unique features of some protein biopolymers that make them ideal for microneedle construction (e.g., excellent mechanical strength, self-adhesion, and self-assembly), as well as the challenges associated with them were reviewed. Altogether, the proteins identified so far seem not only promising for the fabrication of "better" microneedles in the future but also inspiring for designing biomimetic structural biopolymers with ideal characteristics.

Controlled-release in-situ gel forming formulation of tramadol containing chitosan-based pro-nanogels.

Chronic pain is one of the most prevalent health problems worldwide. Tramadol is a synthetic semi-opioid analgesic, interacting with serotonergic, adrenergic and opioid receptors to reduce the pain but its short half-life in vivo may reduce patient compliance in case of chronic pains. To overcome this problem, novel drug delivery systems have been investigated. This study focuses on a chitosan based thermoresponsive in-situ gel forming formulation intended to subcutaneous injection. To evaluate further drug release, a reversed phase high performance liquid chromatography method was developed. Then two formulations (with and without TPP) were optimized by D-optimal plan using Design-Expert statistical software and were characterized in terms of morphology, release phenomenon, texture, swelling and stability as well as in vivo response. AFM images show approximately spherical nanocavities in the homogenous TPP containing gel structure, which explain the different patterns of drug release between the two formulations. This implies that changing TPP concentration can control formation of these cavities and hence drug release rate and kinetics. Not present in the sol state, nanostructures lead to emerge of a new concept: pro-nanogels. Finally, the formulations with proper texture qualities, stability and rapid sol-gel transition in vivo could be a candidate for controlled release of therapeutic agents following subcutaneous injection.