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Vulvovaginal atrophy (VVA), a component of the Genitourinary Syndrome of Menopause, affects the majority of postmenopausal women and those receiving adjuvant endocrine therapy for breast cancer. While topical estrogen therapy is effective, it is contraindicated in women with estrogen receptor-positive breast cancer. Tamoxifen, a selective estrogen receptor modulator, exerts estrogen-like agonistic effects on vaginal epithelium while antagonising breast tissue, making it a promising candidate for local non-hormonal VVA management. This study aimed to develop and characterize two vaginal formulation platforms. A liposomes-in-chitosan-hydrogel (LiH) system and a thermosensitive poloxamer/HPMC gel; using fenofibrate as a physicochemically representative model drug.

Fenofibrate-loaded liposomes were prepared by thin lipid film hydration and extrusion, yielding particles in the 175–215 nm range with low polydispersity and entrapment efficiencies consistently exceeding 85% over two weeks, confirmed by a validated HPLC method. Four gel combinations were prepared at two chitosan concentrations (2.5% and 3.0% w/w) and two liposome loadings (10% and 20% w/w) and assessed visually over three weeks. The 2.5% chitosan gel with 20% liposome loading demonstrated the greatest macroscopic stability and was selected as the candidate formulation. Preliminary Franz cell release data indicated progressive cumulative release of approximately 25% over 6 hours from cells containing liposomes, compared to 2.5% from control, with significant drug retention (~31%) observed in the cellulose acetate membrane. The thermosensitive poloxamer/HPMC gel exhibited sol-gel transition between 22–25°C, confirming thermosensitive behaviour, and demonstrated syringeability and mucoadhesion to bovine vaginal tissue at 37°C.

These results establish a feasible manufacturing and characterization framework for both formulation platforms, providing a foundation for transition to tamoxifen and subsequent ex vivo and in vivo evaluation.