Hydrogel-based drug delivery system designed for chemotherapy-induced alopecia

Abstract

Chemotherapy-induced alopecia (CIA) is a common side effect of many chemotherapeutic anticancer treatments. The only CIA treatment used clinically is a hypothermic cap over the scalp which works through cutaneous vasoconstriction. However, these caps are expensive, often extremely painful, logistically challenging and bulky, and may produce heterogeneous results. In this study, we developed a new bioengineered hydrogel to treat hair follicles during chemotherapy. We physically and chemically characterized Lidocaine (LID) and adrenalone (ADR)-loaded hydrogels and then assessed them using various methods including electron microscopy, rheology, and optical analyses. These studies quantitatively demonstrated desirable hydrogel porosity, rheology/viscosity, thickness, and swelling behavior for topical application. In vitro release studies revealed a biphasic drug release pattern wherein the primary release phase length depended on hydrogel thickness. In vivo murine experiments indicated no ADR and only small amounts of released LID entered blood vessels after topical application based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses, matching the matrix-assisted laser desorption/ionization (MALDI) MS imaging results on drug penetration in skin tissues. Upon hydrogel application, Flemish giant rabbit skin showed significant blood vessel constriction, the primary mechanism-of-action to reduce CIA, suggesting that our hydrogels are likely to be efficacious in avoiding CIA. LID and ADR hydrogels reduced blood vessel diameters by ~39 % and 21 %, respectively. This study thus demonstrates the potential to alleviate CIA using clinically translatable hydrogels.