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Optimizing ibrutinib bioavailability: Formulation and assessment of hydroxypropyl-β-cyclodextrin-based nanosponge delivery systems

Sunitha SampathiSchool of Pharmacy, Vishwakarma University, 411048, Pune, Maharashtra, IndiaNitiraj KulkarniDepartment of Mathematics, Vishwakarma University, Pune, Maharashtra, IndiaD. V. R. N. BhikshapathiTRR College of Pharmacy, Meerpet, Balapur, 500097, Hyderabad, Telangana, IndiaJagadish V. TawadeDepartment of Mathematics, Vishwakarma University, Pune, Maharashtra, IndiaNainaru TarakaramuDepartment of Mathematics, School of Liberal Arts and Sciences, Mohan Babu University, Sree Sainath Nagar, 517102, Tirupati, Andrapradesh, IndiaRzgar Farooq RashidDepartment of Medical Laboratory Science, College of Science, Knowledge University, 44001, Erbil, IraqAziz KubaevDepartment of Maxillofacial Surgery, Samarkand State Medical University, 18 Amir Temur Street, 140100, Samarkand, Uzbekistan

Current Research in Pharmacology and Drug Discoveryjournal2025en

ABI

Annotatsiya

The current research aims to improve the oral bioavailability of ibrutinib (IBR), a class II drug with low solubility, through the formulation of nanosponges (NSPs) that incorporate IBR, utilizing Hydroxypropyl β-cyclodextrin (HPβCD) and 1,1′-carbonyldiimidazole (CDI) as cross-linking agent. IBR-loaded HPβCD-NSPs were formulated by optimizing the molar proportion of HPβCD to CDI, as well as stirring rate and duration using a design-based methodology. The synthesized nanoparticles (NSPs) were examined for size, potential, and entrapment of drug. Characterization was performed by X-ray diffraction analysis, Fourier Transform Infrared Spectroscopy (FT-IR), and Differential Scanning Calorimetry (DSC), to assess compatibility. Permeability studies were conducted, followed by in vitro and in vivo assessments. The optimized IBR-loaded HPβCD NSPs demonstrated a mean particle size of 145.6 ± 6.8 nm, a PDI of 0.170 ± 0.036, and an EE of 71.04 ± 2.40%. Further validation through zeta sizing, microscopic and spectral analysis, release studies, and pharmacokinetic assessments confirmed the optimization. The HPβCD NSPs demonstrated 14.96 times higher AUC0-t (area under the curve) with a Cmax increase of 6.45 times compared to the free drug, indicating a substantial improvement in bioavailability. IBR-loaded HPβCD NSPs offer a promising strategy for improved drug release and bioavailability, which could significantly benefit melanoma treatment. • Developing IBR -loaded, HPβCD nanosponges to address the challenges in cancer therapy. • The optimized NSP’s formulation exhibited low PDI, high ZP, and encapsulation efficiency. • Porous nanostructure of NSPs improved therapeutic efficacy, extended drug release profiles. • Developing HPβCD-NSPs represent a promising platform for targeted cancer drug delivery. • Improving pharmacokinetics could reduce dosing frequency and enhance patient compliance.

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Chronic Lymphocytic Leukemia Research Advancements in Transdermal Drug Delivery Chronic Myeloid Leukemia Treatments

Identifikatorlar

DOI: 10.1016/j.crphar.2025.100213

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