Characterization of novel multifunctional cationic polymeric liposomes formed from octadecyl quaternized carboxymethyl chitosan/cholesterol and drug encapsulation

摘要

The design and construction of effective delivery vectors for drugs is very important. We have discovered that octadecyl quaternized carboxymethyl chitosan (OQCMC) in combination with cholesterol (Chol) could form stable vesicles with structure similar to that of conventional liposomes prepared from phosphatidylcholine/cholesterol (PC/ Chol). Compared to conventional liposomes, our polymeric liposomes formed by OQCMC/Chol have many excellent features, such as good physical and thermal stability, excellent solubility in water, and high effectiveness in drug encapsulation. Trans-activating transcriptional activator protein (TAT peptide) could be connected on the surface of cationic polymeric liposomes by using cross-linking reagent N-hydroxysuccinimidyl-3-(2-pyridyldithio) propionate (SPDP). Also, oil-soluble magnetic nanoparticles were used to verify the bilayer structure of the polymeric liposomes and their ability to solublize hydrophobic materials. Using different preparation methods, OQCMC/Chol could easily be made into nanoscale particles by encapsulating both hydrophilic and hydrophobic components. We have successfully prepared polymeric liposomes encapsulating quantum dots (QDs), superparamagnetic nanoparticles, or both. Vincristine was also encapsulated in the polymeric liposomes with high drug encapsulation efficiency (90.1 %). Vincristine-loaded magnetic polymeric liposomes were stable in aqueous solution and exhibited slow, steady release action over 2 weeks under physiologic pH (7.4). This allows the use of multifunctional cationic polymeric liposomes, such as those developed here from modified chitosan, in various applications such as cancer diagnosis and treatment.