(135d) Fully Bioresorbable Polymeric Vesicles for Therapeutic Applications

Polymersomes (polymer vesicles) have been shown to possess a number of attractive biomaterial properties compared to liposomes (phospholipid vesicles), including prolonged circulation times, increased mechanical stability, as well as the unique ability to incorporate numerous large hydrophobic molecules within their thick lamellar membranes and hydrophilic molecules within their core. We have previously shown the ability to generate two types of self-assembled nano-sized vesicles ranging in size from 100's of nanometers to 10's of microns; one type comprised of a biocompatible diblock copolymer consisting of polyethyleneoxide (PEO) and polybutadine (PBD) and a second fully-bioresorbable vesicle consisting of two FDA-approved building blocks: polyethyleneoxide (PEO) and polycaprolactone (PCL). In addition, we have successfully loaded imaging agents, such as porphyrin-based near infrared (NIR) fluorophores, and therapeutics such as doxorubicin, an anti-neoplastic agent, into these polymersomes and tracked their release in situ and in vivo.

NIR-emissive polymersomes, loaded with porphyrin, can be used for biodistribution studies, to track the location of the polymersomes, and potentially for diagnostic studies. Here, we utilize NIR-emissive polymersomes to determine polymersome biodistribution in tumor bearing mice using a noninvasive small animal optical imaging instrument which detects the NIR fluorescence signal. Passive accumulation of NIR-emissive polymersomes in tumor tissues of mice, as well as other organs, is evidenced. Using porphyrin polymersomes for biodistribution studies will greatly decrease the number of animals required since the location of the polymersomes can be determined without sacrificing animals at multiple time points to perform histology on the excised organs.

Doxorubicin, an anti-neoplastic agent, was encapsulated to serve as a model system for the release of a physiologically relevant compound from the PEO-b-PCL polymersomes. While the kinetics of the release varied at pH 7.4 and pH 5, an initial burst release phase was observed for both pH's followed by a more controlled pH dependent release. The therapeutic potential of doxorubicin loaded polymersomes is shown; drug loaded bioresorbable polymersomes were administered in vivo and their capability to retard tumor growth was assessed using such metrics as tumor size and body weight. Doxorubicin loaded polymersomes were able to retard tumor growth in a live animal on a par with the commercially available DOXIL, liposomal doxorubicin. Furthermore, mouse weights remained within +/-1.5g, for all treatment groups throughout the study. Therefore, this study highlights the enormous promise for polymersomes as in vivo imaging and drug delivery agents.