Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot
XiaoLi Shi,1 Xiao Lin,1 XiangWei Zheng,2 Yi Feng,2 Lan Shen1,2 1College of Chinese Materia Medica, 2Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Repu...
Guardado en:
| Autores principales: | , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Dove Medical Press
2014
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/e14ef93d59404ed3bfb2b57e75022afb |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:e14ef93d59404ed3bfb2b57e75022afb |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:e14ef93d59404ed3bfb2b57e75022afb2021-12-02T03:11:45ZInjectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot1178-2013https://doaj.org/article/e14ef93d59404ed3bfb2b57e75022afb2014-11-01T00:00:00Zhttp://www.dovepress.com/injectable-long-acting-systems-fornbspradix-ophiopogonis-polysaccharid-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 XiaoLi Shi,1 Xiao Lin,1 XiangWei Zheng,2 Yi Feng,2 Lan Shen1,2 1College of Chinese Materia Medica, 2Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China Background: Radix Ophiopogonis polysaccharide (ROP), a highly hydrophilic macromolecule, has a unique anti-ischemic action in the myocardium. One of the main problems with its use is its relatively short half-life in vivo. To solve this problem, injectable long-acting drug delivery systems, which combine mono-PEGylation (PEG, polyethylene glycol) with the in situ formation of poly(D,L-lactide-co-glycolide) copolymer (PLGA) depots, were tested in this study.Methods: Through a moderate coupling reaction between 20 kDa amino-terminated methoxy-PEG and excessive ROP with activated hydroxyls, a long-circulating and bioactive mono-PEGylated ROP was prepared and characterized. A reasonable and applicable range of PLGA formulations loaded with the mono-PEGylated ROP were prepared, characterized, and evaluated in vivo.Results: Relative to ROP, the half-life of which was only 0.5 hours, the conjugate alone, following subcutaneous administration, showed markedly prolonged retention in the systemic circulation, with a mean residence time in vivo of approximately 2.76 days. In combination with in situ-forming PLGA depots, the residence time of the conjugate in vivo was prolonged further. In particular, a long-lasting and steady plasma exposure for nearly a month was achieved by the formulation comprising 40% 30 kDa PLGA in N-methyl-2-pyrrolidone.Conclusion: Long-lasting and steady drug exposure could be achieved using mono-PEGylation in combination with in situ formation of PLGA depots. Such a combination with ROP would be promising for long-term prophylaxis and/or treatment of myocardial ischemia. For high-dose and highly hydrophilic macromolecular drugs like ROP, more than one preparation technology might be needed to achieve week-long or month-long delivery per dosing. Keywords: Radix Ophiopogonis polysaccharide, polyethylene glycol, poly(D,L-lactide-co-glycolide) copolymer, conjugation, in situ-forming systemShi XLLin XZheng XWFeng YShen LDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 5555-5563 (2014) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine (General) R5-920 |
| spellingShingle |
Medicine (General) R5-920 Shi XL Lin X Zheng XW Feng Y Shen L Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot |
| description |
XiaoLi Shi,1 Xiao Lin,1 XiangWei Zheng,2 Yi Feng,2 Lan Shen1,2 1College of Chinese Materia Medica, 2Engineering Research Center of Modern Preparation Technology of TCM of Ministry of Education, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China Background: Radix Ophiopogonis polysaccharide (ROP), a highly hydrophilic macromolecule, has a unique anti-ischemic action in the myocardium. One of the main problems with its use is its relatively short half-life in vivo. To solve this problem, injectable long-acting drug delivery systems, which combine mono-PEGylation (PEG, polyethylene glycol) with the in situ formation of poly(D,L-lactide-co-glycolide) copolymer (PLGA) depots, were tested in this study.Methods: Through a moderate coupling reaction between 20 kDa amino-terminated methoxy-PEG and excessive ROP with activated hydroxyls, a long-circulating and bioactive mono-PEGylated ROP was prepared and characterized. A reasonable and applicable range of PLGA formulations loaded with the mono-PEGylated ROP were prepared, characterized, and evaluated in vivo.Results: Relative to ROP, the half-life of which was only 0.5 hours, the conjugate alone, following subcutaneous administration, showed markedly prolonged retention in the systemic circulation, with a mean residence time in vivo of approximately 2.76 days. In combination with in situ-forming PLGA depots, the residence time of the conjugate in vivo was prolonged further. In particular, a long-lasting and steady plasma exposure for nearly a month was achieved by the formulation comprising 40% 30 kDa PLGA in N-methyl-2-pyrrolidone.Conclusion: Long-lasting and steady drug exposure could be achieved using mono-PEGylation in combination with in situ formation of PLGA depots. Such a combination with ROP would be promising for long-term prophylaxis and/or treatment of myocardial ischemia. For high-dose and highly hydrophilic macromolecular drugs like ROP, more than one preparation technology might be needed to achieve week-long or month-long delivery per dosing. Keywords: Radix Ophiopogonis polysaccharide, polyethylene glycol, poly(D,L-lactide-co-glycolide) copolymer, conjugation, in situ-forming system |
| format |
article |
| author |
Shi XL Lin X Zheng XW Feng Y Shen L |
| author_facet |
Shi XL Lin X Zheng XW Feng Y Shen L |
| author_sort |
Shi XL |
| title |
Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot |
| title_short |
Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot |
| title_full |
Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot |
| title_fullStr |
Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot |
| title_full_unstemmed |
Injectable long-acting systems for Radix Ophiopogonis polysaccharide based on mono-PEGylation and in situ formation of a PLGA depot |
| title_sort |
injectable long-acting systems for radix ophiopogonis polysaccharide based on mono-pegylation and in situ formation of a plga depot |
| publisher |
Dove Medical Press |
| publishDate |
2014 |
| url |
https://doaj.org/article/e14ef93d59404ed3bfb2b57e75022afb |
| work_keys_str_mv |
AT shixl injectablelongactingsystemsfornbspradixophiopogonispolysaccharidebasedonnbspmonopegylationandinsituformationofnbspanbspplgadepot AT linx injectablelongactingsystemsfornbspradixophiopogonispolysaccharidebasedonnbspmonopegylationandinsituformationofnbspanbspplgadepot AT zhengxw injectablelongactingsystemsfornbspradixophiopogonispolysaccharidebasedonnbspmonopegylationandinsituformationofnbspanbspplgadepot AT fengy injectablelongactingsystemsfornbspradixophiopogonispolysaccharidebasedonnbspmonopegylationandinsituformationofnbspanbspplgadepot AT shenl injectablelongactingsystemsfornbspradixophiopogonispolysaccharidebasedonnbspmonopegylationandinsituformationofnbspanbspplgadepot |
| _version_ |
1718401891710271488 |