Search

Abstract: This research is aimed to develop a nanomicelle delivery system in order to enhance the solubility and stability of camptothecin (CPT) in aqueous media. In this case, α,β-poly[(N-carboxybutyl)-l-aspartamide] (PBAsp)–CPT was conjugated by the esterification between PBAsp and 20-OH of CPT, and hence used to fabricate nanomicelles with a particle size between the pore size of blood capillary in normal tissue and that in tumor tissue. It was worthy of note that the drug-loaded system of PBAsp–CPT nanomicelle improved the solubility and stability of CPT in aqueous media. However, with an increase of the CPT loading in PBAsp–CPT, the solubility sharply decreased. Meanwhile, the sizes of PBAsp–CPT nanomicelles showed a tendency of increase. Moreover, the drug release of PBAsp–CPT nanomicelles displayed a linear sustaining profile, and hence resulted in the essential decrease of cytotoxicity to L929 cell line. The assembled nanomicelles based on the PBAsp–CPT conjugates showed a great potential as polymer prodrug of tumor therapy, and the controlled nano-scale might achieve the passive tumor targeting. [Copyright &y& Elsevier]

Abstract: The aim of research is to develop and optimize delivery system for cis-dichlorodiammine platinum(II) (CDDP) based on polymer–metal complex nanomicelles with controllable particle size in order to achieve the passive tumor targeting. In particular, graft copolymers, mPEG–g-α,β-poly [(N-amino acidyl)-dl-aspartamide] (mPEG–g-PAAsp) were synthesized by the ring-opening reaction of polysuccinimide with mPEG-NH2 (M w: 2000 and 5000Da), and then with l-aspartic acid and l-glutamic acid, respectively. mPEG–g-PAAsp–CDDP complex nanomicelles were fabricated from mPEG–g-PAAsp and CDDP. The formation of mPEG–g-PAAsp–CDDP nanomicelles was confirmed by fluorescence spectrophotoscopy, electrical conductivity and particle size measurements. It was found that all the nanomicelles showed spherical shapes with clear core-shell structures and narrow size distributions. Their sizes ranged from 80 to 160nm, suggesting of their passive targeting potential to tumor tissue. With the increase of the molecular weight of mPEG, the sizes of mPEG–g-PAAsp–CDDP micelles showed a tendency to increase. mPEG–g-PAAsp–CDDP nanomicelles showed linear gradual drug release profiles in 40h, suggestion of their sustained drug release behaviors. Compared with CDDP, mPEG–g-PAAsp–CDDP micelles showed essential decreased cytotoxicity to Bel-7402 cell line. [Copyright &y& Elsevier]