{"title":"帕金森病三室微载体药物形状及控释优化设计的仿生方法","authors":"Nidhi Gupta, Debarghya Saha, Vikramsingh Thakur, Shreyash Santosh Yadav, Sandeep Jat, Pramod Kumar, Ashok Kumar Datusalia, Bhabani K. Satapathy* and Sampa Saha*, ","doi":"10.1021/acsabm.4c0114910.1021/acsabm.4c01149","DOIUrl":null,"url":null,"abstract":"<p >Inspired by the intricate cellular morphology and the discoid shape of red blood cells (RBCs), biomimetic tricompartmental microcarriers (TCM) with controlled release profiles were engineered using an electrohydrodynamic-<i>co</i>-jetting technique for efficient management of Parkinson’s disease (PD). While jetting, Levodopa (LD), CD (Carbidopa), and ENT (Entacapone) (3 PD drugs) were directly encapsulated in the three individual compartments of the TCM used for oral administration. The optimal shape and controlled release profiles were obtained by employing the Taguchi orthogonal L9 design-of-experiment approach by systematically varying the processing parameters, i.e., solvent ratio, polymer concentration, and flow rate. The “smaller-the-better” norm for the S/N ratio demonstrated the solvent ratio (DMF content) and polymer concentration as the most influential parameters in ensuring the RBC shape and controlling the release of drugs. Analysis of variance and response surface methodology approach provided insights into the optimal influence of control factors on the response variables. Confirmation experiments further validated the optimized microparticles (<i>P</i><sub>optimized</sub>), demonstrating an error of only ∼0.13% in aspect ratio deviation (AR<sub>DEV</sub>) and ∼19% (within the tolerance limit) in release factor (RF) from the predicted experiment. Moreover, <i>P</i><sub>optimized</sub> exhibits ∼100% encapsulation efficiency of all three PD drugs, with the cumulative release of ∼100% LD, ∼97% CD, and ∼65% ENT within 5 h of the <i>in vitro</i> study. In addition, <i>in vivo</i> studies such as pharmacokinetics (using healthy rats) and pharmacodynamics [using the MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected PD-induced mice model] showed that the TCM can effectively control the release of LD (primary drug) for a prolonged period, thereby promising sustained drug delivery and improved therapeutics outcomes.</p>","PeriodicalId":2,"journal":{"name":"ACS Applied Bio Materials","volume":"8 1","pages":"252–270 252–270"},"PeriodicalIF":4.7000,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Biomimetic Approach for Optimal Designing of the Shape and Controlled Release of Therapeutics from Tricompartmental Microcarriers for Managing Parkinson’s Disease\",\"authors\":\"Nidhi Gupta, Debarghya Saha, Vikramsingh Thakur, Shreyash Santosh Yadav, Sandeep Jat, Pramod Kumar, Ashok Kumar Datusalia, Bhabani K. Satapathy* and Sampa Saha*, \",\"doi\":\"10.1021/acsabm.4c0114910.1021/acsabm.4c01149\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p >Inspired by the intricate cellular morphology and the discoid shape of red blood cells (RBCs), biomimetic tricompartmental microcarriers (TCM) with controlled release profiles were engineered using an electrohydrodynamic-<i>co</i>-jetting technique for efficient management of Parkinson’s disease (PD). While jetting, Levodopa (LD), CD (Carbidopa), and ENT (Entacapone) (3 PD drugs) were directly encapsulated in the three individual compartments of the TCM used for oral administration. The optimal shape and controlled release profiles were obtained by employing the Taguchi orthogonal L9 design-of-experiment approach by systematically varying the processing parameters, i.e., solvent ratio, polymer concentration, and flow rate. The “smaller-the-better” norm for the S/N ratio demonstrated the solvent ratio (DMF content) and polymer concentration as the most influential parameters in ensuring the RBC shape and controlling the release of drugs. Analysis of variance and response surface methodology approach provided insights into the optimal influence of control factors on the response variables. Confirmation experiments further validated the optimized microparticles (<i>P</i><sub>optimized</sub>), demonstrating an error of only ∼0.13% in aspect ratio deviation (AR<sub>DEV</sub>) and ∼19% (within the tolerance limit) in release factor (RF) from the predicted experiment. Moreover, <i>P</i><sub>optimized</sub> exhibits ∼100% encapsulation efficiency of all three PD drugs, with the cumulative release of ∼100% LD, ∼97% CD, and ∼65% ENT within 5 h of the <i>in vitro</i> study. In addition, <i>in vivo</i> studies such as pharmacokinetics (using healthy rats) and pharmacodynamics [using the MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected PD-induced mice model] showed that the TCM can effectively control the release of LD (primary drug) for a prolonged period, thereby promising sustained drug delivery and improved therapeutics outcomes.</p>\",\"PeriodicalId\":2,\"journal\":{\"name\":\"ACS Applied Bio Materials\",\"volume\":\"8 1\",\"pages\":\"252–270 252–270\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2024-12-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"ACS Applied Bio Materials\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://pubs.acs.org/doi/10.1021/acsabm.4c01149\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"MATERIALS SCIENCE, BIOMATERIALS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"ACS Applied Bio Materials","FirstCategoryId":"1085","ListUrlMain":"https://pubs.acs.org/doi/10.1021/acsabm.4c01149","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"MATERIALS SCIENCE, BIOMATERIALS","Score":null,"Total":0}
Biomimetic Approach for Optimal Designing of the Shape and Controlled Release of Therapeutics from Tricompartmental Microcarriers for Managing Parkinson’s Disease
Inspired by the intricate cellular morphology and the discoid shape of red blood cells (RBCs), biomimetic tricompartmental microcarriers (TCM) with controlled release profiles were engineered using an electrohydrodynamic-co-jetting technique for efficient management of Parkinson’s disease (PD). While jetting, Levodopa (LD), CD (Carbidopa), and ENT (Entacapone) (3 PD drugs) were directly encapsulated in the three individual compartments of the TCM used for oral administration. The optimal shape and controlled release profiles were obtained by employing the Taguchi orthogonal L9 design-of-experiment approach by systematically varying the processing parameters, i.e., solvent ratio, polymer concentration, and flow rate. The “smaller-the-better” norm for the S/N ratio demonstrated the solvent ratio (DMF content) and polymer concentration as the most influential parameters in ensuring the RBC shape and controlling the release of drugs. Analysis of variance and response surface methodology approach provided insights into the optimal influence of control factors on the response variables. Confirmation experiments further validated the optimized microparticles (Poptimized), demonstrating an error of only ∼0.13% in aspect ratio deviation (ARDEV) and ∼19% (within the tolerance limit) in release factor (RF) from the predicted experiment. Moreover, Poptimized exhibits ∼100% encapsulation efficiency of all three PD drugs, with the cumulative release of ∼100% LD, ∼97% CD, and ∼65% ENT within 5 h of the in vitro study. In addition, in vivo studies such as pharmacokinetics (using healthy rats) and pharmacodynamics [using the MPTP (methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-injected PD-induced mice model] showed that the TCM can effectively control the release of LD (primary drug) for a prolonged period, thereby promising sustained drug delivery and improved therapeutics outcomes.
期刊介绍:
ACS Applied Bio Materials is an interdisciplinary journal publishing original research covering all aspects of biomaterials and biointerfaces including and beyond the traditional biosensing, biomedical and therapeutic applications.
The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrates knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important bio applications. The journal is specifically interested in work that addresses the relationship between structure and function and assesses the stability and degradation of materials under relevant environmental and biological conditions.