Optimization and Transfollicular Delivery of Finasteride Loaded PLGA Nanoparticles Laden Carbopol Gel for Treatment of Hair Growth Stimulation

Background: One of the frequent side effects of cancer treatment is chemotherapyinduced alopecia (CIA). The psychological discomfort of hair loss may cause patients to stop receiving chemotherapy, lowering the therapy's effectiveness. Finasteride (FNS), a JAK inhibitor, has shown tremendous promise in therapeutic uses for treating baldness. Still, systemic side effects constrained its broad use in alopecia from oral treatment and a low absorption rate at the target site— PLGA-loaded nanoparticles (NPs) for topical delivery of FNS—to overcome these issues. Methods: The nano-precipitation process was used to make FNS-NPs. The independent variables (stabiliser and polymer) were PLGA (X1), P407 (X2), and sonication time (X3). Based on the point prediction method obtainable by the Box Behnken design software, the best FNS-NPs composition was selected. Entrapment efficiency, particle size, zeta potential, and polydispersity index were used to characterize the nanoparticles. Using Carbopol as a polymer, the ideal FNS-NPs composition was further transformed into a gel formulation. The prepared topical gel formulation (FNS-NPs gel) included gel characterization, Dynamic Light Scattering (DLS), Scanning Electron Microscopy (SEM), Powder X-ray Diffraction (PXRD), Differential Scanning Calorimetry (DSC), Fourier Transform Infrared Spectroscopy (FTIR), invitro and in vivo studies. Results: Optimized FNS-NPs (F13) had particle sizes of 175.26±3.85 nm, 0.241±0.11 PDI, 71.04±1.35 % EE, and -33.27±0.39 surface charges. There is no interaction between the drug and the excipients, according to FTIR studies. The FNS were visible in the X-ray diffractogram enclosed in a polymer matrix. The developed FNS-NPs gel formulation shows ideal drug content, viscosity, pH, and spreadability. According to the release and permeation investigation findings, FNS released slowly (68.73±0.94%) but significantly permeated the membrane more than before. In a dose- and time-dependent manner, the produced nanoparticles considerably (p≤0.05) increased FNS delivery compared to the FNS solution. The FNS-NPs gel therapy significantly increases the quantity and size of hair follicles dose-dependently. The effectiveness of the 1% FNSNPs gel and the 2% minoxidil solution were comparable. After 72 hours, the FNS-NPs gel showed no signs of skin irritation. The outcomes, therefore, showed that the trans follicular delivery mechanism of the FNS-NPs gel might stimulate hair growth. Conclusion: These findings imply that the innovative formulation that has been developed has several beneficial properties that make it suitable for FNS dermal delivery in the treatment of alopecia areata