Improving drug retention in liposomes by aging with the aid of glucose.

Zhang, Wenli, Falconer, James R., Baguley, Bruce C., Shaw, John P., Kanamala, Manju, Xu, Hongtao, Wang, Guangji, Liu, Jianping and Wu, Zimei (2016) Improving drug retention in liposomes by aging with the aid of glucose.. International Journal of Pharmaceutics, 505 1-2: 194-203. doi:10.1016/j.ijpharm.2016.03.044

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Author Zhang, Wenli
Falconer, James R.
Baguley, Bruce C.
Shaw, John P.
Kanamala, Manju
Xu, Hongtao
Wang, Guangji
Liu, Jianping
Wu, Zimei
Title Improving drug retention in liposomes by aging with the aid of glucose.
Journal name International Journal of Pharmaceutics   Check publisher's open access policy
ISSN 0378-5173
Publication date 2016-05-30
Sub-type Article (original research)
DOI 10.1016/j.ijpharm.2016.03.044
Open Access Status File (Author Post-print)
Volume 505
Issue 1-2
Start page 194
End page 203
Total pages 10
Place of publication Amsterdam, NX, Netherlands
Publisher Elsevier
Language eng
Abstract This paper describes a novel method to improve drug retention in liposomes for the poorly water-soluble (lipophilic) model drug asulacrine (ASL). ASL was loaded in the aqueous phase of liposomes and the effects of aging conditions and drug loading levels on drug retention were investigated using an in vitro bio-relevant drug release test established in this study. The status of intra-liposomal drug was investigated using differential scanning calorimetry (DSC) and cryo-transmission electron microscopy (cryo-TEM). Pharmacokinetics and venous tolerance of the formulations were simultaneously studied in rabbits following one-hour intravenous infusion via the ear vein. The presence of glucose during aging was found to be crucial to accelerate drug precipitation and to stabilize the liposomal membrane with high drug loading (8.9% over 4.5% w/w) as a prerequisite. Although no drug crystals were detected, DSC showed a lower phase-transition peak in the glucose-assisted aged ASL-liposomes, indicating interaction of phospholipids with the sugar. Cryo-TEM revealed more ‘coffee bean’ like drug precipitate in the ASL-liposomes aged in the glucose solution. In rabbits, these liposomes gave rise to a 1.9 times longer half-life than the fresh liposomes, with no venous irritation observed. Inducing and stabilizing drug precipitation in the liposome cores by aging in the presence of sugar provided an easy approach to improve drug retention in liposomes. The study also highlighted the importance of bio-relevance of in vitro release methods to predict in vivo drug release.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Pharmacy Publications
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Created: Fri, 22 Apr 2016, 23:10:32 EST by James Robert Falconer on behalf of School of Pharmacy