Effect of particle size on in vivo performances of long-acting injectable drug suspension
DC Field | Value | Language |
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dc.contributor.author | Ho, M.J. | - |
dc.contributor.author | Jeong, M.Y. | - |
dc.contributor.author | Jeong, H.T. | - |
dc.contributor.author | Kim, M.S. | - |
dc.contributor.author | Park, H.J. | - |
dc.contributor.author | Kim, D.Y. | - |
dc.contributor.author | Lee, H.C. | - |
dc.contributor.author | Song, W.H. | - |
dc.contributor.author | Kim, C.H. | - |
dc.contributor.author | Lee, C.H. | - |
dc.contributor.author | Choi, Y.W. | - |
dc.contributor.author | Choi, Y.S. | - |
dc.contributor.author | Han, Y.T. | - |
dc.contributor.author | Kang, M.J. | - |
dc.date.accessioned | 2022-01-25T02:40:33Z | - |
dc.date.available | 2022-01-25T02:40:33Z | - |
dc.date.issued | 2022-01 | - |
dc.identifier.issn | 0168-3659 | - |
dc.identifier.issn | 1873-4995 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/54305 | - |
dc.description.abstract | Herein, entecavir-3-palmitate (EV-P), an ester prodrug of entecavir (EV), was employed as a model drug, and the effect of drug particle size on in vivo pharmacokinetic profiles and local inflammatory responses, and those associations were evaluated following intramuscular (IM) injection. EV-P crystals with different median diameters (0.8, 2.3, 6.3, 15.3 and 22.6 μm) were prepared using the anti-solvent crystallization method, with analogous surface charges (−10.7 ~ −4.7 mV), and crystallinity (melting point, 160–170 °C). EV-P particles showed size-dependent in vitro dissolution profiles under sink conditions, exhibiting a high correlation between the median diameter and Hixon-Crowell's release rate constant (r2 = 0.94). Following IM injection in rats (1.44 mg/kg as EV), the pharmacokinetic profile of EV exhibited marked size-dependency; 0.8 μm-sized EV-P particles about 1.6-, 3.6-, and 5.6-folds higher systemic exposure, compared to 6.3, 15.3, and 22.6 μm-sized particles, respectively. This pharmacokinetic pattern, depending on particle size, was also highly associated with histopathological responses in the injected tissue. The smaller EV-P particles (0.8 or 2.3 μm) imparted the larger inflammatory lesion after 3 days, lower infiltration of inflammatory cells, and thinner fibroblastic bands around depots after 4 weeks. Conversely, severe fibrous isolation with increasing particle size augmented the drug remaining at injection site over 4 weeks, impeding the dissolution and systemic exposure. These findings regarding the effects of formulation variable on the in vivo behaviors of long-acting injectable suspension, provide constructive knowledge toward the improved design in poorly water-soluble compounds. © 2021 | - |
dc.format.extent | 15 | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Elsevier B.V. | - |
dc.title | Effect of particle size on in vivo performances of long-acting injectable drug suspension | - |
dc.type | Article | - |
dc.identifier.doi | 10.1016/j.jconrel.2021.12.011 | - |
dc.identifier.bibliographicCitation | Journal of Controlled Release, v.341, pp 533 - 547 | - |
dc.description.isOpenAccess | N | - |
dc.identifier.wosid | 000734883000006 | - |
dc.identifier.scopusid | 2-s2.0-85121213559 | - |
dc.citation.endPage | 547 | - |
dc.citation.startPage | 533 | - |
dc.citation.title | Journal of Controlled Release | - |
dc.citation.volume | 341 | - |
dc.type.docType | Article | - |
dc.publisher.location | 네델란드 | - |
dc.subject.keywordAuthor | Drug crystalline suspension | - |
dc.subject.keywordAuthor | Entecavir-3-palmitate | - |
dc.subject.keywordAuthor | Local inflammation | - |
dc.subject.keywordAuthor | Long-acting injectable | - |
dc.subject.keywordAuthor | Macrophage | - |
dc.subject.keywordAuthor | Particle size | - |
dc.subject.keywordAuthor | Pharmacokinetics | - |
dc.subject.keywordPlus | POLYETHYLENE PARTICLES | - |
dc.subject.keywordPlus | CELLULAR INTERNALIZATION | - |
dc.subject.keywordPlus | MACROPHAGES | - |
dc.subject.keywordPlus | RELEASE | - |
dc.subject.keywordPlus | PHAGOCYTOSIS | - |
dc.subject.keywordPlus | NANOPARTICLES | - |
dc.subject.keywordPlus | RAT | - |
dc.subject.keywordPlus | PHARMACOKINETICS | - |
dc.subject.keywordPlus | MICROSUSPENSION | - |
dc.subject.keywordPlus | MICROSPHERES | - |
dc.relation.journalResearchArea | Chemistry | - |
dc.relation.journalResearchArea | Pharmacology & Pharmacy | - |
dc.relation.journalWebOfScienceCategory | Chemistry, Multidisciplinary | - |
dc.relation.journalWebOfScienceCategory | Pharmacology & Pharmacy | - |
dc.description.journalRegisteredClass | scopus | - |
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