{"title":"Design and optimization of DPC-crosslinked HPβCD nanosponges for entrectinib oral delivery: formulation, characterization, and pharmacokinetic studies","authors":"Konda Sri Chaya Reddy, Darna Bhikshapathi","doi":"10.1186/s43094-024-00680-8","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>In advanced or metastatic cancers characterized by specific genetic alterations, heightened growth and resistance to conventional therapies are common. Targeted treatments like entrectinib (ENT) precisely inhibit aberrant signaling pathways, potentially enhancing outcomes. The objective of this research is to develop and enhance the effectiveness of entrectinib-loaded nanosponge formulations by utilizing hydroxypropyl-β-cyclodextrin (HPβCD) to improve its oral bioavailability.</p><h3>Results</h3><p>The study employed surface response methodology and Design-Expert® software to optimize key formulation variables such as the molar concentration ratio of the polymer and cross-linker, as well as process variables such as stirring speed and duration. Optimization focused on particle size, polydispersity index, and percentage entrapment efficiency. Validation methods encompassed Fourier transform spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), in vitro release studies, and in vivo studies.</p><p>After optimization, ENT-loaded HPβCD NSPs were formulated with a molar ratio (P:CL) of 0.800 mg, stirred at 3000 rpm for 420 min, achieving a desirability of 0.926. Predicted values for PS (particle size), PdI (polydispersity index), and EE % (entrapment efficiency) were 146.98 nm, 0.263, and 88.29%, respectively. The optimized formulation showed a mean size of 151.8 ± 5.6 nm, PDI of 0.233 ± 0.049, and EE of 87.36 ± 1.61%. Further validation through various analyses confirmed the optimization's efficacy, with notable improvements demonstrated in AUC0-t (6.30-fold) and Cmax (4.10 times) compared to the free drug.</p><h3>Conclusion</h3><p>The findings of the study indicated that nanosponges exhibit promise as an effective carrier for delivering entrectinib, addressing for advance tumor effectively by enhancing release and bioavailability in the treatment of cancer.</p></div>","PeriodicalId":577,"journal":{"name":"Future Journal of Pharmaceutical Sciences","volume":"10 1","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://fjps.springeropen.com/counter/pdf/10.1186/s43094-024-00680-8","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Future Journal of Pharmaceutical Sciences","FirstCategoryId":"1085","ListUrlMain":"https://link.springer.com/article/10.1186/s43094-024-00680-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Background
In advanced or metastatic cancers characterized by specific genetic alterations, heightened growth and resistance to conventional therapies are common. Targeted treatments like entrectinib (ENT) precisely inhibit aberrant signaling pathways, potentially enhancing outcomes. The objective of this research is to develop and enhance the effectiveness of entrectinib-loaded nanosponge formulations by utilizing hydroxypropyl-β-cyclodextrin (HPβCD) to improve its oral bioavailability.
Results
The study employed surface response methodology and Design-Expert® software to optimize key formulation variables such as the molar concentration ratio of the polymer and cross-linker, as well as process variables such as stirring speed and duration. Optimization focused on particle size, polydispersity index, and percentage entrapment efficiency. Validation methods encompassed Fourier transform spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), in vitro release studies, and in vivo studies.
After optimization, ENT-loaded HPβCD NSPs were formulated with a molar ratio (P:CL) of 0.800 mg, stirred at 3000 rpm for 420 min, achieving a desirability of 0.926. Predicted values for PS (particle size), PdI (polydispersity index), and EE % (entrapment efficiency) were 146.98 nm, 0.263, and 88.29%, respectively. The optimized formulation showed a mean size of 151.8 ± 5.6 nm, PDI of 0.233 ± 0.049, and EE of 87.36 ± 1.61%. Further validation through various analyses confirmed the optimization's efficacy, with notable improvements demonstrated in AUC0-t (6.30-fold) and Cmax (4.10 times) compared to the free drug.
Conclusion
The findings of the study indicated that nanosponges exhibit promise as an effective carrier for delivering entrectinib, addressing for advance tumor effectively by enhancing release and bioavailability in the treatment of cancer.
期刊介绍：
Future Journal of Pharmaceutical Sciences (FJPS) is the official journal of the Future University in Egypt. It is a peer-reviewed, open access journal which publishes original research articles, review articles and case studies on all aspects of pharmaceutical sciences and technologies, pharmacy practice and related clinical aspects, and pharmacy education. The journal publishes articles covering developments in drug absorption and metabolism, pharmacokinetics and dynamics, drug delivery systems, drug targeting and nano-technology. It also covers development of new systems, methods and techniques in pharmacy education and practice. The scope of the journal also extends to cover advancements in toxicology, cell and molecular biology, biomedical research, clinical and pharmaceutical microbiology, pharmaceutical biotechnology, medicinal chemistry, phytochemistry and nutraceuticals.
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