Androgenetic alopecia (AGA) is a common progressive hair loss disorder driven by elevated dihydrotestosterone (DHT) levels, leading to follicular miniaturization. This study investigated sulforaphane-rich broccoli sprout extract (BSE) as a potential oral therapy for AGA. BSE exhibited dose-dependent proliferative and migratory effects on keratinocytes, dermal fibroblasts, and dermal papilla cells, showing greater in vitro activity than sulforaphane (SFN) and minoxidil under the tested conditions, while maintaining low cytotoxicity. In a testosterone-induced AGA mouse model, oral BSE significantly accelerated hair regrowth, with 20 mg/kg achieving 99% recovery by day 15, alongside increased follicle length, density, and hair weight. Mechanistically, BSE upregulated hepatic and dermal DHT-metabolizing enzymes (Akr1c21, Dhrs9) and activated Wnt/β-catenin signaling in the skin, suggesting dual actions via androgen metabolism modulation and follicular regeneration. Pharmacokinetic analysis revealed prolonged SFN plasma exposure following BSE administration, and in silico docking showed strong binding affinities of key BSE constituents to Akr1c2 and β-catenin. No systemic toxicity was observed in liver histology. These findings indicate that BSE may serve as a safe, effective, and multitargeted natural therapy for AGA. Further clinical studies are needed to validate its efficacy in human populations.

Background/Objectives: This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through a metronomic schedule using a transporter-targeted nanoemulsion (NE), with the goal of improving antitumor efficacy and immune modulation. Methods: AT and DT were co-encapsulated in a NE system (AT/DT-NE#E) incorporating deoxycholic acid–DOTAP (D-TAP), biotin-conjugated phospholipid (Biotin-PE), and d-α-tocopherol polyethylene glycol succinate (TPGS) to exploit bile acid and multivitamin transport pathways and inhibit P-glycoprotein efflux. The optimized NE was characterized physicochemically and evaluated for permeability in artificial membranes and Caco-2/HT29-MTX-E12 monolayers. Pharmacokinetics, tumor suppression, and immune cell infiltration were assessed in vivo using rat and CT26.CL25 mouse models. Results: AT/DT-NE#E showed enhanced permeability of AT and DT by 45.7- and 43.1-fold, respectively, across intestinal cell models and improved oral bioavailability by 118% and 376% compared to free drugs. In vivo, oral metronomic AT/DT-NE#E reduced tumor volume by 65.2%, outperforming intravenous AT/DT. Combination with anti-PD1 therapy achieved a 942% increase in tumor suppression over the control, accompanied by marked increases in tumor-infiltrating CD45⁺, CD4⁺CD3⁺, and CD8⁺CD3⁺ T cells. Conclusions: Oral metronomic administration of AT/DT via a dual-transporter-targeted NE significantly improves drug absorption, tumor inhibition, and immune response. This strategy presents a safe and effective approach for colon cancer therapy, particularly when combined with immunotherapy.

Topical and transdermal dosage forms can localize therapy or provide controlled systemic exposure, but translation is limited by the selective stratum corneum (SC) barrier and post-application changes in formulation. Existing reviews often address individual enhancers or carriers without integrating drug properties, vehicle microstructure, post-application transformation, quality of evidence, and product development constraints. This review fills that gap by comparing passive formulations, chemical permeation enhancers, vesicular and lipid-based carriers, supersaturating systems, and physical barrier bypass technologies within a skin barrier-informed framework. Increased permeation alone does not establish translational value. Passive delivery remains most feasible for potent, moderately lipophilic small molecules. Chemical enhancers are scalable but limited by irritation and drug-dependent compatibility; nanocarriers may improve solubilization and cutaneous deposition but often lack human confirmation; and physical methods broaden delivery to macromolecules while adding device, manufacturing, usability, and regulatory burdens. Solvent evaporation, residual film composition, supersaturation, precipitation, and drug–vehicle affinity further determine the effective post-application driving force. Accordingly, we propose an evidence-ranked framework linking payload properties and target compartment to mechanism, safety, clinical readiness, and regulatory complexity. It distinguishes mechanistic promise from clinically demonstrated delivery and identifies the evidence needed to advance reproducible topical and transdermal products.

Breast cancer treatment remains challenging due to therapeutic resistance and the limited availability of effective molecular targets. We investigated the anticancer effects of sulforaphane (SFN) and broccoli sprout extract (BSE), an SFN-enriched phytochemical formulation, in MCF7 and MDA-MB-231 breast cancer cells. Cell viability, colony formation, and apoptotic responses were evaluated using standard in vitro assays, and underlying mechanisms were examined by flow cytometry and Western blot analysis. BSE and SFN reduced cell viability in a dose-dependent manner, suppressed anchorage-independent growth, and induced apoptosis associated with increased reactive oxygen species (ROS) generation and activation of c-Jun N-terminal kinase and p38 MAPK signaling pathways. These effects were accompanied by mitochondrial depolarization, G2/M cell cycle arrest, and caspase activation. Pharmacokinetic analysis in rats demonstrated that oral administration of BSE resulted in sustained, dose-dependent systemic exposure to SFN. Consistent with these findings, oral BSE significantly inhibited tumor growth in breast cancer xenograft models. Collectively, these results indicate that BSE exerts anticancer effects through coordinated modulation of ROS-associated MAPK signaling, mitochondrial dysfunction, and apoptotic pathways, and may serve as a promising orally administered SFN-containing phytochemical formulation that may function as a delivery matrix for breast cancer management.