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  • Title: Hydroxycamptothecin nanoparticles based on poly/oligo (ethylene glycol): Architecture effects of nanocarriers on antitumor efficacy.
    Author: Guo Y, Wang T, Qiu H, Han M, Dong Z, Wang X, Wang Y.
    Journal: Eur J Pharm Biopharm; 2019 Jan; 134():178-184. PubMed ID: 30529294.
    Abstract:
    Nanoparticles decorated with hydrophilic PEG chains had been emerged as effective drug delivery system due to their biocompatibility and biodegradability, while, the influence of their architecture on antitumor efficacy remained challenging. In this study, the linear poly(ethylene glycol) (PEG45), brush oligo(triethylene glycol) (TEG10), and oligo(ethylene glycol) dendron (G2), which showed the similar molar mass but different architecture, were utilized as nanocarriers to prepare 10-hydroxycamptothecin (HCPT) nanoparticles. It was found that all of three HCPT NPs (PEG45 NPs, TEG10 NPs, and G2 NPs) presented similar DLCs (∼60%), zeta potentials (-13 to -16 mv), and stabilities, meanwhile, the particle sizes, morphologies, release profiles, and anticancer efficacies were affected by the architecture of nanocarriers. Changing the architecture from linear, brush to dendron, the mean particles diameter was decreased from 240 to 170 nm, the sustained releases were elongated from 5 to 9 days. More importantly, the cytotoxicity of G2 NPs based on OEG dendron was enhanced significant comparing with linear PEG45 NPs, the IC50 was decreased almost 10.1-fold (p < 0.01). Besides, the tumor inhibition rate of G2 NPs was 1.7-fold higher than PEG45 NPs, showing significantly optimized antitumor efficacy in vivo. These results suggested the architecture of nanocarriers could affect the antitumor activity, due to the steric hindrance of nanocarriers influence the morphologies of HCPT-loaded nanoparticles.
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