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

Q2 Agricultural and Biological Sciences Current Research in Pharmacology and Drug Discovery Pub Date : 2025-01-01 DOI:10.1016/j.crphar.2025.100213

Sunitha Sampathi , Nitiraj Kulkarni , D.V.R.N. Bhikshapathi , Jagadish V. Tawade , Nainaru Tarakaramu , Rzgar Farooq Rashid , Aziz Kubaev

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusion

IBR-loaded HPβCD NSPs offer a promising strategy for improved drug release and bioavailability, which could significantly benefit melanoma treatment.

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优化依鲁替尼的生物利用度：羟丙基-β-环糊精纳米海绵给药系统的配方和评估

本研究旨在以羟丙基β-环糊精（HPβCD）和1,1′-羰基二咪唑（CDI）为交联剂，制备含有IBR的纳米海绵（nsp），以提高IBR的口服生物利用度。IBR是一类低溶解度的II类药物。方法采用基于设计的方法，通过优化HPβCD与CDI的摩尔比、搅拌速率和搅拌时间，制备负载sibr的HPβCD- nsps。研究了合成的纳米颗粒（NSPs）的大小、潜力和药物的包裹性。通过x射线衍射分析、傅里叶变换红外光谱（FT-IR）和差示扫描量热法（DSC）进行表征，以评估相容性。进行了渗透性研究，随后进行了体外和体内评估。结果优化后的ibr负载的HPβCD NSPs平均粒径为145.6±6.8 nm， PDI为0.170±0.036，EE为71.04±2.40%。通过zeta尺寸、显微镜和光谱分析、释放研究和药代动力学评估进一步验证了该优化方案。与游离药物相比，HPβCD NSPs的AUC0-t（曲线下面积）提高了14.96倍，Cmax提高了6.45倍，表明其生物利用度有了显著提高。结论ibr负载的HPβCD NSPs具有改善药物释放和生物利用度的良好策略，可显著促进黑色素瘤的治疗。

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