ArticleBMC pharmacology & toxicology2026
In-vitro pharmacological and cytotoxic evaluation of genipin-crosslinked human serum albumin nanoparticles loaded with methyltestosterone in MCF-7 breast cancer cells.
Article in BMC pharmacology & toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundBreast cancer remains one of the leading causes of cancer-related mortality among women worldwide. Although methyltestosterone (MT) has demonstrated therapeutic potential in hormone-responsive breast cancer, its clinical application may be limited by poor aqueous solubility and non-specific distribution. Albumin-based nanocarriers may enhance drug stability and intracellular availability. This study aimed to develop genipin-crosslinked human serum albumin (HSA) nanoparticles loaded with MT and to evaluate their physicochemical properties, release behavior, and in-vitro pharmacological and cytotoxic effects in MCF-7 breast cancer cells.
methodsMT-loaded HSA nanoparticles were prepared using the desolvation method followed by genipin crosslinking. Particle size, polydispersity index (PDI), and zeta potential were determined by dynamic light scattering (DLS), while morphology and crystallinity were evaluated using SEM and XRD analysis. Drug loading (DL) and encapsulation efficiency (EE) were quantified spectrophotometrically. In-vitro release was assessed under different pH conditions (5.5, 6.8, and 7.4). Cytotoxicity and pharmacological activity were evaluated in MCF-7 cells using MTT, LDH, and TUNEL assays. Statistical analysis was performed using one-way ANOVA (p < 0.05).
resultsThe formulated MT-HSA nanoparticles exhibited a mean diameter of 83 nm (PDI 0.25) and a zeta potential of - 16.3 mV, indicating uniform nanoscale distribution and moderate colloidal stability. Encapsulation efficiency and drug loading were 77% and 11%, respectively. Sustained and pH-dependent drug release was observed over 100 h, with higher release under acidic conditions (83% at pH 5.5). MT-HSA nanoparticles significantly reduced MCF-7 cell viability compared with free MT (p < 0.05), accompanied by increased LDH release and higher apoptotic index in TUNEL assays. Unloaded HSA nanoparticles showed negligible cytotoxicity. The formulation remained physically stable for two months at 4 °C.
conclusionsGenipin-crosslinked MT-HSA nanoparticles demonstrated improved in-vitro pharmacological efficacy, enhanced cytotoxic and pro-apoptotic activity compared with free methyltestosterone, and favorable carrier biocompatibility. These findings support albumin-based nanoencapsulation as a promising strategy for optimizing steroid-based therapy in hormone-responsive breast cancer, although further in-vivo studies are required to confirm translational potential.
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