Formulation and Evaluation of Bosentan Monohydrate-loaded Liposome-based Dissolving Microneedle Array Patches

Background: Pulmonary arterial hypertension is controlled by the dual endothelin receptor antagonist bosentan monohydrate. Recent advances in microneedle technology offer controlled, prolonged drug release. Objectives: This study formulated and evaluated a bosentan monohydrate-loaded liposome-based dissolved microneedles (MNs) array patch. Materials and Methods: Bosentan monohydrate liposomes were prepared using the ethanol injection method and incorporated into microneedle patches. The dissolving microneedles (DMNs) were prepared by using a two-step casting method. The first 3D computer-aided design (CAD)-designed master mold for the MNs was fabricated using SLA 3D printing and replicated using polydimethylsiloxane (PDMS). The mold was filled with a mixture of polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP-K30), PEG-400, and bosentan-loaded liposomes, then centrifuged and dried. Optimization using response surface methodology (RSM) focused on particle size, zeta potential (ZP), and entrapment efficiency (EE). Results: The optimized liposomes had an average size of 238.06 nm, a ZP of −34.33 mV, and an EE of 75.3%. Morphological analyses via microscopy and scanning electron microscopy (SEM) confirmed spherical liposomes with smooth surfaces. Drug release studies indicated a controlled release over time, reaching approximately 90% cumulative drug release (CDR) at 600 min. Kinetic modeling showed a zero-order release pattern. Mechanical testing of the MNs demonstrated a fracture point at 0.42 N, ensuring adequate strength for skin penetration. Ex vivo tests on rat skin confirmed nearly 100% penetration of the 15 × 15 microneedle array. Conclusion: The study concludes that the optimized formulation of liposomal-loaded DMNs is easy to administer, non-invasive, and biodegradable, offering a promising approach for controlled drug release in managing pulmonary hypertension (PH).