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Surface Modification of Nanoparticles Enhances Drug Delivery to the Brain and Improves Survival in a Glioblastoma Multiforme Murine Model.
Wiwatchaitawee, Kanawat; Ebeid, Kareem; Quarterman, Juliana C; Naguib, Youssef; Ali, Md Yousuf; Oliva, Claudia; Griguer, Corinne; Salem, Aliasger K.
Afiliação
  • Wiwatchaitawee K; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United States.
  • Ebeid K; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United States.
  • Quarterman JC; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Minia 61519, Egypt.
  • Naguib Y; Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Manufacturing, Deraya University, New Minia City, Minia 61768, Egypt.
  • Ali MY; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United States.
  • Oliva C; Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United States.
  • Griguer C; Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Minia 61519, Egypt.
  • Salem AK; Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Manufacturing, Deraya University, New Minia City, Minia 61768, Egypt.
Bioconjug Chem ; 33(11): 1957-1972, 2022 11 16.
Article em En | MEDLINE | ID: mdl-35041398
ABSTRACT
Glioblastoma multiforme (GBM) is the most malignant type of brain tumor and has an extremely poor prognosis. Current treatment protocols lack favorable outcomes, and alternative treatments with superior efficacy are needed. In this study, we demonstrate that loading paclitaxel (PTX) in a polymeric, nanoparticulate delivery system is capable of improving its brain accumulation and therapeutic activity. We independently incorporated two different positively charged surface modifiers, poly(amidoamine) (PAMAM) and poly(ethylenimine) (PEI), onto poly(lactic-co-glycolic acid) (PLGA)-polyethylene glycol (PEG), PLGA-PEG, nanoparticles (NPs) using a modified nanoprecipitation technique that assures the formation of nanosized particles while exposing the positively charged polymer on the surface. The prepared NPs underwent comprehensive analyses of their size, charge, in vitro permeability against a BBB cell line, and in vivo biodistribution. Our results demonstrated the successful fabrication of positively charged NPs using PAMAM or PEI. Importantly, significant improvement in brain accumulation (in vivo) was associated with NPs containing PAMAM compared to unmodified NPs or NPs containing PEI. Finally, the efficacy of PAMAM-modified NPs loaded with PTX was evaluated with orthotopic human GBM xenografts in a mouse model, and the data demonstrated improved survival and equivalent safety compared to soluble PTX. Our data substantiate the importance of surface chemistry on the magnitude of NP accumulation in the brain and pave the way for further in vivo evaluation of chemotherapeutic drugs against GBM that have previously been overlooked because of their limited ability to cross the BBB.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glioblastoma / Nanopartículas Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Glioblastoma / Nanopartículas Tipo de estudo: Guideline Limite: Animals / Humans Idioma: En Ano de publicação: 2022 Tipo de documento: Article