Cellular internalization mechanisms of polyanhydride particles

Implications for rational design of drug delivery vehicles

Yashdeep Phanse, Paul Lueth, Amanda Ramer-Tait, Brenda R. Carrillo-Conde, Michael J. Wannemuehler, Balaji Narasimhan, Bryan H. Bellaire

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Polyanhydride nanoparticles have emerged as a versatile delivery platform, due to their ability to encapsulate diverse drugs, immunogens, antibodies, and proteins. However, mechanistic studies on the effects of particle chemistry interactions with immune cells have yet to be described. Understanding the mechanism by which these particles are internalized by immune cells will enable rational selection of delivery vehicles for specific applications. In the present study, the internalization, mechanism(s) of uptake by monocytes, and intracellular fate of polyanhydride nanoparticles were evaluated using copolymers based on 1,6-bis(p-carboxyphenoxy)hexane (CPH), sebacic acid (SA), and 1,8-bis(p-carboxyphenoxy)- 3,6-dioxaoctane (CPTEG). The results showed that 20:80 CPH:SA and 20:80 CPTEG:CPH nanoparticles were internalized to a greater extent by monocytes as compared to the 50:50 CPH:SA and 50:50 CPTEH:CPH nanoparticles. Further, cytochalasin-D treatment of cells inhibited uptake of all the particles, regardless of chemistry, indicating that actinmediated uptake is the primary mechanism of cellular entry for these particles. The insights gained from these studies were used to identify lead nanoparticle formulations to enhance treatment of intracellular bacterial infections. The use of doxycycline-loaded nanoparticles exhibited enhanced therapeutic efficacy compared to soluble drug in treating monocyte monolayers infected with the virulent intracellular pathogen Brucella abortus. Altogether, these studies demonstrate how rational design and selection of nanoscale delivery platforms can be used for a wide spectrum of biomedical applications.

Original languageEnglish (US)
Pages (from-to)1544-1552
Number of pages9
JournalJournal of Biomedical Nanotechnology
Volume12
Issue number7
DOIs
StatePublished - Jul 1 2016

Fingerprint

Polyanhydrides
Drug Design
Drug delivery
Nanoparticles
Hexanes
Hexane
Monocytes
Acids
Brucella abortus
Cytochalasin D
Doxycycline
Pathogens
Bacterial Infections
Antibodies
Pharmaceutical Preparations
Monolayers
Copolymers
Cells
Proteins

Keywords

  • Brucell
  • Drug Delivery
  • Inhibitors
  • Nanoparticles
  • Polyanhydrides
  • Uptake Mechanism

ASJC Scopus subject areas

  • Materials Science(all)
  • Bioengineering
  • Biomedical Engineering
  • Medicine (miscellaneous)
  • Pharmaceutical Science

Cite this

Cellular internalization mechanisms of polyanhydride particles : Implications for rational design of drug delivery vehicles. / Phanse, Yashdeep; Lueth, Paul; Ramer-Tait, Amanda; Carrillo-Conde, Brenda R.; Wannemuehler, Michael J.; Narasimhan, Balaji; Bellaire, Bryan H.

In: Journal of Biomedical Nanotechnology, Vol. 12, No. 7, 01.07.2016, p. 1544-1552.

Research output: Contribution to journalArticle

Phanse, Yashdeep ; Lueth, Paul ; Ramer-Tait, Amanda ; Carrillo-Conde, Brenda R. ; Wannemuehler, Michael J. ; Narasimhan, Balaji ; Bellaire, Bryan H. / Cellular internalization mechanisms of polyanhydride particles : Implications for rational design of drug delivery vehicles. In: Journal of Biomedical Nanotechnology. 2016 ; Vol. 12, No. 7. pp. 1544-1552.
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