Rapid Transport of Deformation-tuned Nanoparticles Across Biological Hydrogels and Cellular Barriers


Authors: M. Yu, L. Xu, F. Tian, Q. Su, N. Zheng and Y. Yang

Journal: Nature communications

DOI: 10.6084/m9.figshare.6152189

Publication - Abstract

July 04, 2018

Small Molecule Drugs Other Formulations Polymeric Nanoparticles
To optimally penetrate biological hydrogels such as mucus and the tumor interstitial matrix, nanoparticles (NPs) require physicochemical properties that would typically preclude cellular uptake, resulting in inefficient drug delivery. Here, we demonstrate that (poly(lactic-co-glycolic acid) (PLGA) core)-(lipid shell) NPs with moderate rigidity display enhanced diffusivity through mucus compared with some synthetic mucus penetration particles (MPPs), achieving a mucosal and tumor penetrating capability superior to that of both their soft and hard counterparts. Orally administered semi-elastic NPs efficiently overcome multiple intestinal barriers, and result in increased bioavailability of doxorubicin (Dox) (up to 8 fold) compared to Dox solution. Molecular dynamics simulations and super-resolution microscopy reveal that the semi-elastic NPs deform into ellipsoids, which enables rotation-facilitated penetration. In contrast, rigid NPs cannot deform, and overly soft NPs are impeded by interactions with the hydrogel network. Modifying particle rigidity may improve the efficacy of NP-based drugs, and can be applicable to other barriers.

limit search to this category
Advanced Search

Advanced Search

close
  • Publications
  • Application Notes
  • Posters
  • Workshops
  • Videos & Webinars
  • Articles
Search

Browse by Category

  • Application
    • Diagnostic and Imaging
    • Genetic Medicine
    • Hematology
    • Metabolic Disorders
    • Neuroscience
    • Oncology
    • Skeletal Disorders
    • Targeted Drug Delivery
    • Vaccines
    • Other Applications
    • Cell therapy
  • Formulation
    • Liposomes
    • Nucleic Acid Lipid Nanoparticles
    • Polymeric Nanoparticles
    • Other Formulations
  • Payload
    • DNA
    • microRNA
    • mRNA
    • siRNA
    • Small Molecule Drugs
    • Other Payloads


related content

Publication - Abstract

Nov 21, 2016
Nanoscale

Cationic Switchable Lipids: pH-triggered Molecular Switch for siRNA Delivery

W. Viricel, S. Poirier, A. Mbarek, R.M. Derbali, G. Mayer and J. Leblond

Other Formulations Nucleic Acid Lipid Nanoparticles siRNA
A pH-sensitive molecular switch able to change its conformation upon protonation at endosomal pH values is embedded into the structure of cationic lipidoid materials, thus conferring endosomal escape properties. Involvement of the conformational switch in the endosomal escape pro...
Read More


Publication - Abstract

Oct 10, 2018
Drug Delivery and Translational Research

Rapid Optimization of Liposome Characteristics Using a Combined Microfluidics and Design-of-experiment Approach

M. Sedighi, S. Sieber, F. Rahimi, M.A. Shahbazi, A.H. Rezayan, J. Huwyler and D. Witzigmann

Liposomes Small Molecule Drugs
Liposomes have attracted much attention as the first nanoformulations entering the clinic. The optimization of physicochemical properties of liposomes during nanomedicine development however is time-consuming and challenging despite great advances in formulation development. Here...
Read More


Sign Up and Stay Informed
Sign up today to automatically receive new Precision NanoSystems application notes, conference posters, relevant science publications, and webinar invites.
Sign Up