Polymersome für die medizinische Anwendung : Vesikel basierend auf Aktivester-Blockcopolymeren und Blockcopolypeptiden als Wirkstoffträger in der Nanomedizin
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Abstract
The objective of this work was the development of polymersomes based on P(PFPMA)-b-P(LMA) active ester polymers as well as vesicles from the block co-polypept(o)id P(Glu(OBn))-b-P(Sar) and to evaluate their applicability as nano-sized drug delivery vehicles. Those polymers were contemplated to be versatilely functionalizable and biocompatible materials as an alternative to polyethylene glycol.
Vesicle formation was achieved by aminolysis of the active ester repeating units using 2,3-dihydroxypropylamine (DHPA) to form P(DHPMA). In contrast, the ag-gre¬gation of polymers based on widely-used, but less hydrophilic P(HPMA) did not yield vesicles. The polymersomes proved to be highly stable and were loaded with hydrophilic cargo by Dual Centrifugation with efficiencies as high as 35 %. Further¬more, the polymers were equipped with several types of functional groups that can play an important role in drug delivery. For example, a mannose targeting ligand was attached and a hydrolyzable monomer was copolymerized as a pH-dependent stimulus for vesicle disintegration.
Cell assays confirmed that the new type of P(DHPMA) polymers were nontoxic, with cell viabilities comparable to P(HPMA). The corresponding blockcopolymer vesicles, too, did not cause any cytotoxic effects even at high concentrations. Fur-ther¬more, no aggregation induced by protein adsorption did occur in human blood serum. Moreover, vesicles labeled with the mannose ligand displayed a significantly increased cell uptake compared to non-mannosylated polymersomes.
As for P(Glu(OBn))-b-P(Sar), only aggregates of micellar morphology had been reported so far. This work describes the first successful formation of vesicles from this material. They, too, were loaded with hydrophilic cargo at high efficiencies. Additionally, their potential to serve as a carrier for CpG oligonucleotides was confirmed by the activation of dendritic cells and the proliferation of T-cells.
The obtained results verify the applicability of both polymer systems to form readi¬ly functionalizable and biocompatible vesicles. They demonstrate P(DHPMA)-b-P(LMA) and P(Glu(OBn))-b-P(Sar) to be promising carriers of water-soluble drugs without requiring any substance-specific ligation chemistry.