Journal article
Surface Modification of Nanoparticles Enhances Drug Delivery to the Brain and Improves Survival in a Glioblastoma Multiforme Murine Model
Bioconjugate chemistry, Vol.33(11), pp.1957-1972
11/16/2022
DOI: 10.1021/acs.bioconjchem.1c00479
PMCID: PMC9662320
PMID: 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-
-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.
Details
- Title: Subtitle
- Surface Modification of Nanoparticles Enhances Drug Delivery to the Brain and Improves Survival in a Glioblastoma Multiforme Murine Model
- Creators
- Kanawat Wiwatchaitawee - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United StatesKareem Ebeid - Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Manufacturing, Deraya University, New Minia City, Minia 61768, EgyptJuliana C Quarterman - Department of Pharmaceutical Sciences and Experimental Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, United StatesYoussef Naguib - Department of Pharmaceutics, Faculty of Pharmacy and Pharmaceutical Manufacturing, Deraya University, New Minia City, Minia 61768, EgyptMd Yousuf Ali - Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United StatesClaudia Oliva - Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United StatesCorinne Griguer - Department of Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242, United StatesAliasger K Salem - Holden Comprehensive Cancer Center, University of Iowa, Iowa City, Iowa 52242, United States
- Resource Type
- Journal article
- Publication Details
- Bioconjugate chemistry, Vol.33(11), pp.1957-1972
- DOI
- 10.1021/acs.bioconjchem.1c00479
- PMID
- 35041398
- PMCID
- PMC9662320
- NLM abbreviation
- Bioconjug Chem
- ISSN
- 1043-1802
- eISSN
- 1520-4812
- Grant note
- name: NIH, award: P30 CA086862
- Language
- English
- Electronic publication date
- 01/18/2022
- Date published
- 11/16/2022
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics; Radiation Oncology; Craniofacial Anomalies Research Center; Dental Research; Chemical and Biochemical Engineering
- Record Identifier
- 9984216690402771
Metrics
12 Record Views