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A Highly Translatable Dual-arm Local Delivery Strategy To Achieve Widespread Therapeutic Coverage in Healthy and Tumor-bearing Brain Tissues.
Negron, Karina; Kwak, Gijung; Wang, Heng; Li, Haolin; Huang, Yi-Ting; Chen, Shun-Wen; Tyler, Betty; Eberhart, Charles G; Hanes, Justin; Suk, Jung Soo.
Affiliation
  • Negron K; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Kwak G; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
  • Wang H; Center for Nanomedicine at the Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Li H; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Huang YT; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • Chen SW; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • Tyler B; Department of Neuroscience and Behavioral Biology, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • Eberhart CG; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD, 21218, USA.
  • Hanes J; Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
  • Suk JS; Department of Ophthalmology, Johns Hopkins University School of Medicine, Baltimore, MD, 21231, USA.
Small ; 19(11): e2207278, 2023 03.
Article in En | MEDLINE | ID: mdl-36651002
ABSTRACT
Drug delivery nanoparticles (NPs) based entirely on materials generally recognized as safe that provide widespread parenchymal distribution following intracranial administration via convection-enhanced delivery (CED) are introduced. Poly(lactic-co-glycolic acid) (PLGA) NPs are coated with various poloxamers, including F68, F98, or F127, via physical adsorption to render particle surfaces non-adhesive, thereby resisting interactions with brain extracellular matrix. F127-coated PLGA (F127/PLGA) NPs provide markedly greater distribution in healthy rat brains compared to uncoated NPs and widespread coverage in orthotopically-established brain tumors. Distribution analysis of variously-sized F127/PLGA NPs determines the average rat brain tissue porosity to be between 135 and 170 nm while revealing unprecedented brain coverage of larger F127/PLGA NPs with an aid of hydraulic pressure provided by CED. Importantly, F127/PLGA NPs can be lyophilized for long-term storage without compromising their ability to penetrate the brain tissue. Further, 65- and 200-nm F127/PLGA NPs lyophilized-reconstituted and administered in a moderately hyperosmolar infusate solution show further enhance particle dissemination in the brain via osmotically-driven enlargement of the brain tissue porosity. Combination of F127/PLGA NPs and osmotic tissue modulation provides a means with a clear regulatory path to maximize the brain distribution of large NPs that enable greater drug loading and prolong drug release.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Nanoparticles / Neoplasms Limits: Animals Language: En Journal: Small Journal subject: ENGENHARIA BIOMEDICA Year: 2023 Type: Article Affiliation country: United States
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Nanoparticles / Neoplasms Limits: Animals Language: En Journal: Small Journal subject: ENGENHARIA BIOMEDICA Year: 2023 Type: Article Affiliation country: United States