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Degradable PEG-folate coated poly(DMAEA-co-BA)phosphazene-based polyplexes exhibit receptor-specific gene expression.

J Luten¹, M J van Steenbergen, M C Lok

¹Department of Pharmaceutics, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of Pharmaceutical Sciences, Utrecht University, P.O. Box 80.082, 3508 TB Utrecht, The Netherlands.

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences

|January 22, 2008

Summary

Researchers developed a new biodegradable polyphosphazene for targeted delivery. Folate-coated nanoparticles showed enhanced transfection in cancer cells, with improved biocompatibility for potential in vivo applications.

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Area of Science:

Biomaterials Science
Nanotechnology
Gene Delivery

Background:

Development of cationic biodegradable polyphosphazenes with primary and tertiary amine side groups.
Modification of polyphosphazene-based polyplexes with polyethylene glycol (PEG) and PEG-folate for nanoparticle formulation.

Purpose of the Study:

To evaluate the transfection efficiency and biocompatibility of novel polyphosphazene-based polyplexes.
To investigate the role of folate receptor-mediated targeting in enhancing gene delivery.
To assess the hemocompatibility of the developed polyplexes for in vivo applications.

Main Methods:

Synthesis of poly(2-dimethylaminoethylamine-co-diaminobutane)phosphazene (poly(DMAEA-co-BA)phosphazene).
Coupling of PEG and PEG-folate to polyplexes.
In vitro cell culture experiments (transfection assays, cytotoxicity, confocal microscopy) and erythrocyte aggregation tests.

Main Results:

Small, near-neutral polyplexes (100-120 nm) were formed with low cytotoxicity.
PEG-folate coated polyplexes exhibited a 3-fold higher transfection efficiency in OVCAR 3 cells compared to PEGylated polyplexes.
Targeted polyplexes showed folate receptor-dependent uptake and significantly improved hemocompatibility compared to uncoated polyplexes.

Conclusions:

Targeted delivery using folate-functionalized poly(DMAEA-co-BA)phosphazene polyplexes enhances transfection efficiency.
The improved hemocompatibility of PEGylated and folate-targeted polyplexes suggests suitability for in vivo gene delivery applications.