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Article: Interplay between Amphiphilic Stabilizers and Cholesterol in the Stabilization of Itraconazole Nanoparticles Prepared by Flash Nanoprecipitation

TitleInterplay between Amphiphilic Stabilizers and Cholesterol in the Stabilization of Itraconazole Nanoparticles Prepared by Flash Nanoprecipitation
Authors
KeywordsAmphiphilic stabilizers
Cholesterol
Flash nanoprecipitation
Itraconazole nanoparticles
Physical stability
Solubility parameter
Issue Date2018
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/mpohbp/index.html
Citation
Molecular Pharmaceutics, 2018, v. 16 n. 1, p. 195-204 How to Cite?
AbstractWhile flash nanoprecipitation (FNP) has proven to be an extremely rapid and highly efficient nanoparticle fabrication process for hydrophobic drugs, physical instability associated with nonequilibrium molecular orientation of amphiphilic stabilizers (ASs) in nanoparticles remains a major snag in the general application of this nanotechnology, particularly for a drug with ACDLog P in the range of ∼2–9. This study was aimed at elucidating the costabilizing role of cholesterol (CLT) in the FNP of AS-stabilized nanoparticles of itraconazole (ITZ), a model drug with an ACDLog P of 4.35 ± 1.22 and log P of 5.66. The presence of CLT was shown to reduce the initial particle size and markedly improve the short-term storage stability of ITZ nanoparticles. The stability-enhancement by CLT can be linked to its higher miscibility or stronger interaction with the AS hydrophobic moiety than with ITZ (as reflected by the absolute differences of their solubility parameter values). Surface analyses employing X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) suggest that, through the coprecipitation of CLT with ITZ to form a mixed hydrophobic drug core, the CLT molecules that are exposed on the core surface serve to afford a stronger and more timely surface anchorage of the AS hydrophobic moieties, thereby facilitating the rearrangement of AS molecules toward the stable micelle-like structure. The present findings offer a mechanistic insight into the interplay between amphiphilic stabilizer and costabilizer in enhancing the physical stability of drug nanoparticles and may carry important implications for the development of more stable and efficacious nanoparticle therapeutics.
Persistent Identifierhttp://hdl.handle.net/10722/266098
ISSN
2017 Impact Factor: 4.556
2015 SCImago Journal Rankings: 1.681
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorWan, KY-
dc.contributor.authorWong, SN-
dc.contributor.authorWong, KW-
dc.contributor.authorChow, SF-
dc.contributor.authorChow, AHL-
dc.date.accessioned2018-12-17T02:16:47Z-
dc.date.available2018-12-17T02:16:47Z-
dc.date.issued2018-
dc.identifier.citationMolecular Pharmaceutics, 2018, v. 16 n. 1, p. 195-204-
dc.identifier.issn1543-8384-
dc.identifier.urihttp://hdl.handle.net/10722/266098-
dc.description.abstractWhile flash nanoprecipitation (FNP) has proven to be an extremely rapid and highly efficient nanoparticle fabrication process for hydrophobic drugs, physical instability associated with nonequilibrium molecular orientation of amphiphilic stabilizers (ASs) in nanoparticles remains a major snag in the general application of this nanotechnology, particularly for a drug with ACDLog P in the range of ∼2–9. This study was aimed at elucidating the costabilizing role of cholesterol (CLT) in the FNP of AS-stabilized nanoparticles of itraconazole (ITZ), a model drug with an ACDLog P of 4.35 ± 1.22 and log P of 5.66. The presence of CLT was shown to reduce the initial particle size and markedly improve the short-term storage stability of ITZ nanoparticles. The stability-enhancement by CLT can be linked to its higher miscibility or stronger interaction with the AS hydrophobic moiety than with ITZ (as reflected by the absolute differences of their solubility parameter values). Surface analyses employing X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM) suggest that, through the coprecipitation of CLT with ITZ to form a mixed hydrophobic drug core, the CLT molecules that are exposed on the core surface serve to afford a stronger and more timely surface anchorage of the AS hydrophobic moieties, thereby facilitating the rearrangement of AS molecules toward the stable micelle-like structure. The present findings offer a mechanistic insight into the interplay between amphiphilic stabilizer and costabilizer in enhancing the physical stability of drug nanoparticles and may carry important implications for the development of more stable and efficacious nanoparticle therapeutics.-
dc.languageeng-
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/mpohbp/index.html-
dc.relation.ispartofMolecular Pharmaceutics-
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in Molecular Pharmaceutics, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/acs.molpharmaceut.8b00945-
dc.subjectAmphiphilic stabilizers-
dc.subjectCholesterol-
dc.subjectFlash nanoprecipitation-
dc.subjectItraconazole nanoparticles-
dc.subjectPhysical stability-
dc.subjectSolubility parameter-
dc.titleInterplay between Amphiphilic Stabilizers and Cholesterol in the Stabilization of Itraconazole Nanoparticles Prepared by Flash Nanoprecipitation-
dc.typeArticle-
dc.identifier.emailChow, SF: asfchow@hku.hk-
dc.identifier.authorityChow, SF=rp02296-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1021/acs.molpharmaceut.8b00945-
dc.identifier.pmid30525643-
dc.identifier.scopuseid_2-s2.0-85059358212-
dc.identifier.hkuros296471-
dc.identifier.volume16-
dc.identifier.issue1-
dc.identifier.spage195-
dc.identifier.epage204-
dc.identifier.isiWOS:000455288900017-
dc.publisher.placeUnited States-

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