Shell crosslinked nanoencapsulate were prepared via crosslinking reaction between double hydrophilic grafted copolymers poly(N-isopropyl acrylamide)-co-poly(L-lysine) (PNIPAm-co-PLLys) and natural crosslinking agent genipin. These shell crosslinked nanoencapsulate possess spherical structures and the hydrodynamic radiuses are about 18.5 nm to 37.7 nm. Drug-loaded shell crosslinked nanoencapsulate were applied as drug carriers. Model drug methotrexate (MTX) were loaded into polymeric nanoencapsulate with different loading ratios (polymer / MTX = 10 / 0.5 and 10 / 1.0), then crosslinking agent genipin was added into micelle solution to form drug-loaded shell crosslinked nanoencapsulate. Entrapment efficiency and drug loading content of the drug-loaded shell crosslinked nanoencapsulate are about 12.66 wt% to 20.1 wt% and 0.84 wt% to 1.28 wt%, respectively. In-vitro drug release experiments of drug-loaded shell crosslinked nanoencapsulate were carried out in pH 7.4 phosphate buffer solution at 37 °C. All of these samples possess burst release in initial 8 h, and final accumulate MTX release amounts are about 71% to 97%.
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