Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle
Yanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd,...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2012-12-01
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| Series: | International Journal of Nanomedicine |
| Online Access: | http://www.dovepress.com/improvement-of-in-vivo-efficacy-of-recombinant-human-erythropoietin-by-a11817 |
| _version_ | 1818433406422220800 |
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| author | Shi YN Huang W Liang RC Sun KX Zhang FX Liu WH Li YX |
| author_facet | Shi YN Huang W Liang RC Sun KX Zhang FX Liu WH Li YX |
| author_sort | Shi YN |
| collection | DOAJ |
| description | Yanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd, Yantai, China; 3School of Pharmacy, Yantai University, Yantai, China*These authors contributed equally to this workAbstract: To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO), rhEPO was successfully formulated into poly(ethylene glycol)–poly(d,l-lactide) (PEG–PLA) di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3) and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.Keywords: rhEPO, PEG–PLA micelle, in vitro, pharmacokinetics, pharmacodynamics |
| first_indexed | 2024-12-14T16:20:35Z |
| format | Article |
| id | doaj.art-002c171b43954946822879cc63ad2285 |
| institution | Directory Open Access Journal |
| issn | 1176-9114 1178-2013 |
| language | English |
| last_indexed | 2024-12-14T16:20:35Z |
| publishDate | 2012-12-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | International Journal of Nanomedicine |
| spelling | doaj.art-002c171b43954946822879cc63ad22852022-12-21T22:54:48ZengDove Medical PressInternational Journal of Nanomedicine1176-91141178-20132012-12-012013default111Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelleShi YNHuang WLiang RCSun KXZhang FXLiu WHLi YXYanan Shi,1,2,* Wan Huang,1,* Rongcai Liang,1–3 Kaoxiang Sun,2,3 Fangxi Zhang,2,3 Wanhui Liu,2,3 Youxin Li1–31College of Life Science, Jilin University, Changchun, China; 2State Key Laboratory of Long-acting and Targeting Drug Delivery System, Luye Pharmaceutical Co, Ltd, Yantai, China; 3School of Pharmacy, Yantai University, Yantai, China*These authors contributed equally to this workAbstract: To improve the pharmacokinetics and stability of recombinant human erythropoietin (rhEPO), rhEPO was successfully formulated into poly(ethylene glycol)–poly(d,l-lactide) (PEG–PLA) di-block copolymeric micelles at diameters ranging from 60 to 200 nm with narrow polydispersity indices (PDIs; PDI < 0.3) and trace amount of protein aggregation. The zeta potential of the spherical micelles was in the range of −3.78 to 4.65 mV and the highest encapsulation efficiency of rhEPO in the PEG–PLA micelles was about 80%. In vitro release profiles indicated that the stability of rhEPO in the micelles was improved significantly and only a trace amount of aggregate was found. Pharmacokinetic studies in rats showed highly enhanced plasma retention time of the rhEPO-loaded PEG-PLA micelles in comparison with the native rhEPO group. Increased hemoglobin concentrations were also found in the rat study. Native polyacrylamide gel electrophoresis results demonstrated that rhEPO was successfully encapsulated into the micelles, which was stable in phosphate buffered saline with different pHs and concentrations of NaCl. Therefore, PEG–PLA micelles can be a potential protein drug delivery system.Keywords: rhEPO, PEG–PLA micelle, in vitro, pharmacokinetics, pharmacodynamicshttp://www.dovepress.com/improvement-of-in-vivo-efficacy-of-recombinant-human-erythropoietin-by-a11817 |
| spellingShingle | Shi YN Huang W Liang RC Sun KX Zhang FX Liu WH Li YX Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle International Journal of Nanomedicine |
| title | Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle |
| title_full | Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle |
| title_fullStr | Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle |
| title_full_unstemmed | Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle |
| title_short | Improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in PEG–PLA micelle |
| title_sort | improvement of in vivo efficacy of recombinant human erythropoietin by encapsulation in peg amp ndash pla micelle |
| url | http://www.dovepress.com/improvement-of-in-vivo-efficacy-of-recombinant-human-erythropoietin-by-a11817 |
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