Encapsulation of progesterone in reishi mushroom composite for optimized hormone replacement and targeted anticancer therapy

Conventional hormone replacement therapy (HRT) and hormone-dependent cancer treatments face significant challenges, including poor bioavailability, rapid metabolism, and adverse side effects of progesterone, as well as limited targeting efficiency and systemic toxicity. To address these issues, this study develops an innovative progesterone-reishi mushroom (<i>Ganoderma lucidum</i>) composite, leveraging the natural bioactive properties of reishi mushrooms to enhance therapeutic efficacy. The composite was prepared by encapsulating progesterone within the reishi mushroom matrix, achieving a high loading efficiency of 98.10%. Characterization using FTIR, SEM, XRD, and UV-Vis confirmed successful encapsulation and interaction between progesterone and the mushroom matrix. <i>In vitro</i> release studies demonstrated a sustained and controlled release profile, with 88.25% of progesterone released over 48 hours, compared to the rapid and complete release of free progesterone within 2-4 hours. Kinetic modeling revealed a non-Fickian diffusion mechanism, indicating a synergistic interaction between the hormone and the mushroom matrix. <i>In vitro</i> cytotoxicity assays on MCF-7 breast cancer cells showed that the composite exhibited enhanced anticancer activity, with an IC₅₀ of 81.11 μg mL^-1, significantly lower than free progesterone (IC₅₀ = 123.12 μg mL^-1). Molecular docking studies highlighted the strong binding affinities of ganoderic acid A (a bioactive compound from reishi mushrooms) and progesterone with key receptors (PCL-2, PI3K, PR, ERα), suggesting potential synergistic effects in hormone regulation and cancer inhibition. Antimicrobial assays revealed the composite's potent activity against Gram-positive pathogens, such as <i>Streptococcus agalactiae</i> (MIC = 41.60 μg mL^-1) and <i>Staphylococcus aureus</i> (MIC = 52.10 μg mL^-1), with bactericidal effects (MBC/MIC < 4). Accelerated stability testing (40 ± 2 °C/75 ± 5% RH, 6 months) showed >94% progesterone retention, sustained release, stable colloidal properties, and minimal loss of antimicrobial activity against bacteria and <i>Candida albicans</i>, confirming its stability and efficacy. This research demonstrates the promise of combining natural bioactive compounds with synthetic hormones for targeted, effective therapies. The progesterone-reishi mushroom composite offers a dual-action approach, integrating hormonal regulation with anticancer and antimicrobial properties, paving the way for novel treatments in women's health and cancer therapy.