{"title":"冷冻干燥负载异烟肼聚ε-己内酯纳米颗粒的制备与优化。","authors":"Eknath Kole, Yuvraj Pawara, Atul Chaudhari, Aniruddha Chatterjee, Jitendra Naik","doi":"10.5599/admet.2774","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Microfluidic nanoprecipitation followed by freeze-drying would yield uniformly sized, stable nanoparticles by preserving their physicochemical property without compromising therapeutic performance. The isoniazid (INH)-loaded poly-<i>ε</i>-caprolactone (PCL) nanoparticles could be developed using a microfluidic technique for the management of tuberculosis.</p><p><strong>Experimental approach: </strong>The INH-loaded nanoparticles were fabricated via a microreactor-assisted nanoprecipitation method and optimization using a design of experiments factorial design approach. The resulting INH-PCL nanoformulation was characterized for particle size, polydispersity index (PDI), zeta potential (surface charge), Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis and field emission scanning electron microscope.</p><p><strong>Key results: </strong>The optimized nanoparticles exhibited an average particle size (248.4 ± 5.372 nm) and high encapsulation efficiency (82.26 ± 4.36 %). Thermal and spectroscopic analyses confirmed the absence of drug-polymer interactions, ensuring formulation integrity; stability studies under accelerated conditions demonstrated negligible changes in particle size, PDI, and zeta potential over the period of 6 months, indicating robust colloidal stability. A scanning electron microscopy study revealed rod-shaped nanoparticles with smooth surfaces. Lyophilization (freeze-drying) enhanced long-term stability, yielding a readily re-dispersible powder (reconstitution index ~1.066). Following diffusion-controlled kinetics, in vitro drug release studies in phosphate buffer saline (pH 7.4) showed sustained drug release (92.45 % cumulative release over 48 h).</p><p><strong>Conclusion: </strong>Our results confirm that the INH-loaded PCL nanoformulation combines excellent stability, high drug-loading capacity, and sustained release, key attributes of effective tuberculosis therapy.</p>","PeriodicalId":7259,"journal":{"name":"ADMET and DMPK","volume":"13 4","pages":"2774"},"PeriodicalIF":4.3000,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335300/pdf/","citationCount":"0","resultStr":"{\"title\":\"Fabrication and optimization of freeze-dried isoniazid-loaded poly-<i>ε</i>-caprolactone nanoparticles.\",\"authors\":\"Eknath Kole, Yuvraj Pawara, Atul Chaudhari, Aniruddha Chatterjee, Jitendra Naik\",\"doi\":\"10.5599/admet.2774\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Microfluidic nanoprecipitation followed by freeze-drying would yield uniformly sized, stable nanoparticles by preserving their physicochemical property without compromising therapeutic performance. The isoniazid (INH)-loaded poly-<i>ε</i>-caprolactone (PCL) nanoparticles could be developed using a microfluidic technique for the management of tuberculosis.</p><p><strong>Experimental approach: </strong>The INH-loaded nanoparticles were fabricated via a microreactor-assisted nanoprecipitation method and optimization using a design of experiments factorial design approach. The resulting INH-PCL nanoformulation was characterized for particle size, polydispersity index (PDI), zeta potential (surface charge), Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis and field emission scanning electron microscope.</p><p><strong>Key results: </strong>The optimized nanoparticles exhibited an average particle size (248.4 ± 5.372 nm) and high encapsulation efficiency (82.26 ± 4.36 %). Thermal and spectroscopic analyses confirmed the absence of drug-polymer interactions, ensuring formulation integrity; stability studies under accelerated conditions demonstrated negligible changes in particle size, PDI, and zeta potential over the period of 6 months, indicating robust colloidal stability. A scanning electron microscopy study revealed rod-shaped nanoparticles with smooth surfaces. Lyophilization (freeze-drying) enhanced long-term stability, yielding a readily re-dispersible powder (reconstitution index ~1.066). Following diffusion-controlled kinetics, in vitro drug release studies in phosphate buffer saline (pH 7.4) showed sustained drug release (92.45 % cumulative release over 48 h).</p><p><strong>Conclusion: </strong>Our results confirm that the INH-loaded PCL nanoformulation combines excellent stability, high drug-loading capacity, and sustained release, key attributes of effective tuberculosis therapy.</p>\",\"PeriodicalId\":7259,\"journal\":{\"name\":\"ADMET and DMPK\",\"volume\":\"13 4\",\"pages\":\"2774\"},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2025-07-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12335300/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ADMET and DMPK\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5599/admet.2774\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ADMET and DMPK","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5599/admet.2774","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Fabrication and optimization of freeze-dried isoniazid-loaded poly-ε-caprolactone nanoparticles.
Background: Microfluidic nanoprecipitation followed by freeze-drying would yield uniformly sized, stable nanoparticles by preserving their physicochemical property without compromising therapeutic performance. The isoniazid (INH)-loaded poly-ε-caprolactone (PCL) nanoparticles could be developed using a microfluidic technique for the management of tuberculosis.
Experimental approach: The INH-loaded nanoparticles were fabricated via a microreactor-assisted nanoprecipitation method and optimization using a design of experiments factorial design approach. The resulting INH-PCL nanoformulation was characterized for particle size, polydispersity index (PDI), zeta potential (surface charge), Fourier-transform infrared spectroscopy, differential scanning calorimetry, X-ray diffraction analysis and field emission scanning electron microscope.
Key results: The optimized nanoparticles exhibited an average particle size (248.4 ± 5.372 nm) and high encapsulation efficiency (82.26 ± 4.36 %). Thermal and spectroscopic analyses confirmed the absence of drug-polymer interactions, ensuring formulation integrity; stability studies under accelerated conditions demonstrated negligible changes in particle size, PDI, and zeta potential over the period of 6 months, indicating robust colloidal stability. A scanning electron microscopy study revealed rod-shaped nanoparticles with smooth surfaces. Lyophilization (freeze-drying) enhanced long-term stability, yielding a readily re-dispersible powder (reconstitution index ~1.066). Following diffusion-controlled kinetics, in vitro drug release studies in phosphate buffer saline (pH 7.4) showed sustained drug release (92.45 % cumulative release over 48 h).
Conclusion: Our results confirm that the INH-loaded PCL nanoformulation combines excellent stability, high drug-loading capacity, and sustained release, key attributes of effective tuberculosis therapy.
期刊介绍:
ADMET and DMPK is an open access journal devoted to the rapid dissemination of new and original scientific results in all areas of absorption, distribution, metabolism, excretion, toxicology and pharmacokinetics of drugs. ADMET and DMPK publishes the following types of contributions: - Original research papers - Feature articles - Review articles - Short communications and Notes - Letters to Editors - Book reviews The scope of the Journal involves, but is not limited to, the following areas: - physico-chemical properties of drugs and methods of their determination - drug permeabilities - drug absorption - drug-drug, drug-protein, drug-membrane and drug-DNA interactions - chemical stability and degradations of drugs - instrumental methods in ADMET - drug metablic processes - routes of administration and excretion of drug - pharmacokinetic/pharmacodynamic study - quantitative structure activity/property relationship - ADME/PK modelling - Toxicology screening - Transporter identification and study