Co-Encapsulation of Mitoxantrone and β-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia
Identifieur interne : 000183 ( an2020/Analysis ); précédent : 000182; suivant : 000184Co-Encapsulation of Mitoxantrone and β-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia
Auteurs : Kambere Amerigos Daddy J. C. ; Minglei Chen ; Faisal Raza ; Yanyu Xiao ; Zhigui Su ; Qineng PingSource :
- Pharmaceutics [ 1999-4923 ] ; 2020.
Abstract
Multidrug resistance (MDR) due to P-glycoprotein (P-gp) overexpression is a major obstacle to successful leukemia chemotherapy. The combination of anticancer chemotherapy with a chemosensitizer of P-gp inhibitor is promising to overcome MDR, generate synergistic effects, and maximize the treatment effect. Herein, we co-encapsulated a chemotherapeutic drug of mitoxantrone (MTO) and a P-gp inhibitor of β-elemene (βE) in solid lipid nanoparticles (MTO/βE-SLNs) for reversing MDR in leukemia. The MTO/βE-SLNs with about 120 nm particle size possessed good colloidal stability and sustained release behavior. For the cellular uptake study, doxorubicin (DOX) was used as a fluorescence probe to construct SLNs. The results revealed that MTO/βE-SLNs could be effectively internalized by both K562/DOX and K562 cells through the pathway of caveolate-mediated endocytosis. Under the optimized combination ratio of MTO and βE, the in vitro cytotoxicity study indicated that MTO/βE-SLNs showed a better antitumor efficacy in both K562/DOX and K562 cells than other MTO formulations. The enhanced cytotoxicity of MTO/βE-SLNs was due to the increased cellular uptake and blockage of intracellular ATP production and P-gp efflux by βE. More importantly, the in vivo studies revealed that MTO/βE-SLNs could significantly prolong the circulation time and increase plasma half-life of both MTO and βE, accumulate into tumor and exhibit a much higher anti-leukemia effect with MDR than other MTO formulations. These findings suggest MTO/βE-SLNs as a potential combined therapeutic strategy for overcoming MDR in leukemia.
Url:
DOI: 10.3390/pharmaceutics12020191
PubMed: 32102214
PubMed Central: 7076650
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Co-Encapsulation of Mitoxantrone and β-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia</title><author><name sortKey="Amerigos Daddy J C, Kambere" sort="Amerigos Daddy J C, Kambere" uniqKey="Amerigos Daddy J C K" first="Kambere" last="Amerigos Daddy J. C.">Kambere Amerigos Daddy J. C.</name></author><author><name sortKey="Chen, Minglei" sort="Chen, Minglei" uniqKey="Chen M" first="Minglei" last="Chen">Minglei Chen</name></author><author><name sortKey="Raza, Faisal" sort="Raza, Faisal" uniqKey="Raza F" first="Faisal" last="Raza">Faisal Raza</name></author><author><name sortKey="Xiao, Yanyu" sort="Xiao, Yanyu" uniqKey="Xiao Y" first="Yanyu" last="Xiao">Yanyu Xiao</name></author><author><name sortKey="Su, Zhigui" sort="Su, Zhigui" uniqKey="Su Z" first="Zhigui" last="Su">Zhigui Su</name></author><author><name sortKey="Ping, Qineng" sort="Ping, Qineng" uniqKey="Ping Q" first="Qineng" last="Ping">Qineng Ping</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">32102214</idno><idno type="pmc">7076650</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7076650</idno><idno type="RBID">PMC:7076650</idno><idno type="doi">10.3390/pharmaceutics12020191</idno><date when="2020">2020</date><idno type="wicri:Area/Pmc/Corpus">000794</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000794</idno><idno type="wicri:Area/Pmc/Curation">000794</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000794</idno><idno type="wicri:Area/Pmc/Checkpoint">000171</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000171</idno><idno type="wicri:Area/Ncbi/Merge">000F65</idno><idno type="wicri:Area/Ncbi/Curation">000F65</idno><idno type="wicri:Area/Ncbi/Checkpoint">000F65</idno><idno type="wicri:Area/Main/Merge">000183</idno><idno type="wicri:Area/Main/Curation">000183</idno><idno type="wicri:Area/Main/Exploration">000183</idno><idno type="wicri:Area/an2020/Extraction">000183</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Co-Encapsulation of Mitoxantrone and β-Elemene in Solid Lipid Nanoparticles to Overcome Multidrug Resistance in Leukemia</title><author><name sortKey="Amerigos Daddy J C, Kambere" sort="Amerigos Daddy J C, Kambere" uniqKey="Amerigos Daddy J C K" first="Kambere" last="Amerigos Daddy J. C.">Kambere Amerigos Daddy J. C.</name></author><author><name sortKey="Chen, Minglei" sort="Chen, Minglei" uniqKey="Chen M" first="Minglei" last="Chen">Minglei Chen</name></author><author><name sortKey="Raza, Faisal" sort="Raza, Faisal" uniqKey="Raza F" first="Faisal" last="Raza">Faisal Raza</name></author><author><name sortKey="Xiao, Yanyu" sort="Xiao, Yanyu" uniqKey="Xiao Y" first="Yanyu" last="Xiao">Yanyu Xiao</name></author><author><name sortKey="Su, Zhigui" sort="Su, Zhigui" uniqKey="Su Z" first="Zhigui" last="Su">Zhigui Su</name></author><author><name sortKey="Ping, Qineng" sort="Ping, Qineng" uniqKey="Ping Q" first="Qineng" last="Ping">Qineng Ping</name></author></analytic><series><title level="j">Pharmaceutics</title><idno type="eISSN">1999-4923</idno><imprint><date when="2020">2020</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Multidrug resistance (MDR) due to P-glycoprotein (P-gp) overexpression is a major obstacle to successful leukemia chemotherapy. The combination of anticancer chemotherapy with a chemosensitizer of P-gp inhibitor is promising to overcome MDR, generate synergistic effects, and maximize the treatment effect. Herein, we co-encapsulated a chemotherapeutic drug of mitoxantrone (MTO) and a P-gp inhibitor of β-elemene (βE) in solid lipid nanoparticles (MTO/βE-SLNs) for reversing MDR in leukemia. The MTO/βE-SLNs with about 120 nm particle size possessed good colloidal stability and sustained release behavior. For the cellular uptake study, doxorubicin (DOX) was used as a fluorescence probe to construct SLNs. The results revealed that MTO/βE-SLNs could be effectively internalized by both K562/DOX and K562 cells through the pathway of caveolate-mediated endocytosis. Under the optimized combination ratio of MTO and βE, the in vitro cytotoxicity study indicated that MTO/βE-SLNs showed a better antitumor efficacy in both K562/DOX and K562 cells than other MTO formulations. The enhanced cytotoxicity of MTO/βE-SLNs was due to the increased cellular uptake and blockage of intracellular ATP production and P-gp efflux by βE. More importantly, the in vivo studies revealed that MTO/βE-SLNs could significantly prolong the circulation time and increase plasma half-life of both MTO and βE, accumulate into tumor and exhibit a much higher anti-leukemia effect with MDR than other MTO formulations. These findings suggest MTO/βE-SLNs as a potential combined therapeutic strategy for overcoming MDR in leukemia.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Enache, M" uniqKey="Enache M">M. Enache</name></author><author><name sortKey="Toader, A M" uniqKey="Toader A">A.M. Toader</name></author><author><name sortKey="Enache, M I" uniqKey="Enache M">M.I. Enache</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Filipczak, N" uniqKey="Filipczak N">N. 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C.</name><name sortKey="Chen, Minglei" sort="Chen, Minglei" uniqKey="Chen M" first="Minglei" last="Chen">Minglei Chen</name><name sortKey="Ping, Qineng" sort="Ping, Qineng" uniqKey="Ping Q" first="Qineng" last="Ping">Qineng Ping</name><name sortKey="Raza, Faisal" sort="Raza, Faisal" uniqKey="Raza F" first="Faisal" last="Raza">Faisal Raza</name><name sortKey="Su, Zhigui" sort="Su, Zhigui" uniqKey="Su Z" first="Zhigui" last="Su">Zhigui Su</name><name sortKey="Xiao, Yanyu" sort="Xiao, Yanyu" uniqKey="Xiao Y" first="Yanyu" last="Xiao">Yanyu Xiao</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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