Work

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

Year: 2025

Type: article

Abstract: 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).

Source: Journal of Pharmacology and Pharmacotherapeutics

DOI: 10.1177/0976500x251327444