{"title":"In vitro and in vivo evaluation of dual Clofazimine and Verapamil loaded PLGA nanoparticles.","authors":"Bhavneet Kaur, Maninder Kaur, Priyanca Ahlawat, Sadhna Sharma","doi":"10.1007/s12291-022-01062-8","DOIUrl":null,"url":null,"abstract":"<p><p>Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, combination of two drugs in a nanoformulation was prepared. Clofazimine targets type 2 NADH dehydrogenase of the electron transport chain, and Verapamil inhibits various mycobacterial efflux pumps. The nanotechnology approach was adopted to overcome limitations associated with administration of free form of drugs by using poly (D, L-lactic-co-glycolic acid) as a polymer. Nanoparticles were prepared by oil/water single emulsion solvent evaporation procedure and characterized by various techniques. The results thus highlighted that developed nanoparticles were spherical with nano range size (200-450 nm). Fourier transform infrared spectroscopy revealed successful encapsulation of drugs in developed nanoformulations. Drugs in combination showed higher encapsulation efficiency and percentage drug loading capacity as compared to individual drug nanoformulations. Also, reduced toxicity of nanoformulation was observed in hemolysis assay as compared to free drugs. <i>Ex-vivo</i> analysis demonstrated efficient uptake of rhodamine encapsulated nanoparticles by THP-1 cells, while <i>in-vivo</i> results revealed sustained drug release of nanoformulation as compared to free drugs in combination. Therefore, we were able to achieve development of a single nanoformulation encapsulating Clofazimine and Verapamil in combination. Based on these findings, future studies can be designed to explore the potential of co-encapsulated Clofazimine and Verapamil nanoparticles in management of tuberculosis.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s12291-022-01062-8.</p>","PeriodicalId":13280,"journal":{"name":"Indian Journal of Clinical Biochemistry","volume":"38 4","pages":"466-474"},"PeriodicalIF":1.5000,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10516816/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Indian Journal of Clinical Biochemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1007/s12291-022-01062-8","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/9/6 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Combination therapy may counter the risk caused by efflux pumps mediated resistance developed by mycobacteria with a concomitant increase of the bactericidal effect of anti-TB drugs. In the present study, combination of two drugs in a nanoformulation was prepared. Clofazimine targets type 2 NADH dehydrogenase of the electron transport chain, and Verapamil inhibits various mycobacterial efflux pumps. The nanotechnology approach was adopted to overcome limitations associated with administration of free form of drugs by using poly (D, L-lactic-co-glycolic acid) as a polymer. Nanoparticles were prepared by oil/water single emulsion solvent evaporation procedure and characterized by various techniques. The results thus highlighted that developed nanoparticles were spherical with nano range size (200-450 nm). Fourier transform infrared spectroscopy revealed successful encapsulation of drugs in developed nanoformulations. Drugs in combination showed higher encapsulation efficiency and percentage drug loading capacity as compared to individual drug nanoformulations. Also, reduced toxicity of nanoformulation was observed in hemolysis assay as compared to free drugs. Ex-vivo analysis demonstrated efficient uptake of rhodamine encapsulated nanoparticles by THP-1 cells, while in-vivo results revealed sustained drug release of nanoformulation as compared to free drugs in combination. Therefore, we were able to achieve development of a single nanoformulation encapsulating Clofazimine and Verapamil in combination. Based on these findings, future studies can be designed to explore the potential of co-encapsulated Clofazimine and Verapamil nanoparticles in management of tuberculosis.
Supplementary information: The online version contains supplementary material available at 10.1007/s12291-022-01062-8.
期刊介绍：
The primary mission of the journal is to promote improvement in the health and well-being of community through the development and practice of clinical biochemistry and dissemination of knowledge and recent advances in this discipline among professionals, diagnostics industry, government and non-government organizations. Indian Journal of Clinical Biochemistry (IJCB) publishes peer reviewed articles that contribute to the existing knowledge in all fields of Clinical biochemistry, either experimental or theoretical, particularly deal with the applications of biochemistry, molecular biology, genetics, biotechnology, and immunology to the diagnosis, treatment, monitoring and prevention of human diseases. The articles published also include those covering the analytical and molecular diagnostic techniques, instrumentation, data processing, quality assurance and accreditation aspects of the clinical investigations in which chemistry has played a major role, or laboratory animal studies with biochemical and clinical relevance.
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