کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1427579 986869 2006 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis and characterization of novel poly(ethylene glycol)-lipid conjugates suitable for use in drug delivery
موضوعات مرتبط
مهندسی و علوم پایه مهندسی مواد بیومتریال
پیش نمایش صفحه اول مقاله
Synthesis and characterization of novel poly(ethylene glycol)-lipid conjugates suitable for use in drug delivery
چکیده انگلیسی

Liposomal formulations have been used to encapsulate and deliver a wide variety of therapeutic and diagnostic agents. Their circulation can be prolonged by the addition of neutral, hydrophilic polymers such as poly(ethylene glycol) (PEG) to the outer surface. An extended circulation lifetime allows them to take advantage of the enhanced permeability and retention effect (EPR), resulting in increased delivery to target sites. Incorporation of PEG also prevents aggregation and aids in the formation of uniform, small mono-disperse particles. This is often accomplished with the use of PEG-lipid conjugates, PEG molecules with a hydrophobic domain to anchor them into the liposomal bilayer upon formulation.Here we present data showing that some commonly used PEG-lipids are chemically unstable due to the presence of carboxylic ester bonds. This instability limits their utility in aqueous environments common to many liposomal preparations. To address this problem, we designed and synthesized three alternative PEG-lipids. Using SPLP (PEG-stabilized liposomal vesicles encapsulating plasmid DNA) as a model system, we investigated the properties of the novel PEG-lipids. An accelerated stability study was conducted at 37 °C for 42 days to confirm chemical stability and an in vivo model was used to assess the pharmacokinetics, toxicity and activity of the SPLP. We show that the novel PEG-lipids are more stable in liposomal formulation, less toxic upon systemic administration, and accordingly, are suitable replacements for the PEG-lipids described previously.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Controlled Release - Volume 112, Issue 2, 15 May 2006, Pages 280–290
نویسندگان
, , , , ,