Controlled Delivery of Paclitaxel via Stable Synthetic Protein Nanoparticles

Abstract: Despite decades of intense research, glioma remains a disease for which no adequate clinical treatment exists. Given the ongoing therapeutic failures of conventional treatment approaches, nanomedicine may offer alternative options because it can increase the bioavailability of drugs and alter their pharmacokinetics. Here, a new type of synthetic protein nanoparticles (SPNPs) is reported that allow for effective loading and controlled release of the potent cancer drug, paclitaxel (PTX) – a drug that so far has been unsuccessful in glioma treatment due to hydrophobicity, low solubility, and associated delivery challenges. SPNPs are prepared by electrohydrodynamic (EHD) jetting of dilute solutions of PTX‐loaded albumin made by high‐pressure homogenization. After EHD jetting, PTX SPNPs possess a dry diameter of 165 ± 44 nm, hydrated diameter of 297 ± 102 nm, and a zeta potential of −19 ± 8 mV in water. For the SPNP formulation with a total PTX loading of 9.4%, the loading efficiency is 94%, and controlled release of PTX is observed over two weeks (6% burst release). PTX SPNPs are more potent (68% lethality) than free PTX (45% lethality using 0.2% dimethyl sulfoxide). PTX SPNPs in combination with IR show a significant survival benefit in glioma‐bearing mouse models, avoid adverse liver toxicity, and maintain a normal brain architecture. Immunohistochemistry reveals a dramatic tumor size reduction including 40% long‐term survivors without discernible signs of tumor. Using flexibly engineered SPNPs, this work outlines an efficient strategy for the delivery of hydrophobic drugs that are otherwise notoriously hard to deliver.

Location
Deutsche Nationalbibliothek Frankfurt am Main
Extent
Online-Ressource
Language
Englisch

Bibliographic citation
Controlled Delivery of Paclitaxel via Stable Synthetic Protein Nanoparticles ; day:27 ; month:06 ; year:2024 ; extent:11
Advanced therapeutics ; (27.06.2024) (gesamt 11)

Creator
Mauser, Ava
Waibel, Isabel
Banerjee, Kaushik
Mujeeb, Anzar A.
Gan, Jingyao
Lee, Sophia
Brown, William
Lang, Nigel
Gregory, Jason
Raymond, Jeffery
Franzeb, Matthias
Schwendeman, Anna
Castro, Maria G.
Lahann, Joerg

DOI
10.1002/adtp.202400208
URN
urn:nbn:de:101:1-2406271427340.439025722225
Rights
Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
Last update
14.08.2025, 11:01 AM CEST

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Associated

  • Mauser, Ava
  • Waibel, Isabel
  • Banerjee, Kaushik
  • Mujeeb, Anzar A.
  • Gan, Jingyao
  • Lee, Sophia
  • Brown, William
  • Lang, Nigel
  • Gregory, Jason
  • Raymond, Jeffery
  • Franzeb, Matthias
  • Schwendeman, Anna
  • Castro, Maria G.
  • Lahann, Joerg

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