Surfactant-polymer nanoparticles: A novel platform for sustained and enhanced cellular delivery of water-soluble molecules

Mahesh D. Chavanpatil, Ayman Khdair, Jayanth Panyam

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Purpose. Nanoparticles, drug carriers in the sub-micron size range, can enhance the therapeutic efficacy of encapsulated drug by increasing and sustaining the delivery of the drug inside the cell. However, the use of nanoparticles for small molecular weight, water-soluble drugs has been limited by poor drug encapsulation efficiency and rapid release of the encapsulated drug. Here we report enhanced cellular delivery of water-soluble molecules using novel Aerosol OT™ (AOT)-alginate nanoparticles recently developed in our laboratory. Materials and Methods. AOT-alginate nanoparticles were formulated using emulsion-crosslinking technology. Rhodamine and doxorubicin were used as model water-soluble molecules. Kinetics and mechanism of nanoparticle-mediated cellular drug delivery and therapeutic efficacy of nanoparticle-encapsulated doxorubicin were evaluated in two model breast cancer cell lines. Results. AOT-alginate nanoparticles demonstrated sustained release of doxorubicin over a 15-day period in vitro. Cell culture studies indicated that nanoparticles enhanced the cellular delivery of rhodamine by about two-tenfold compared to drug in solution. Nanoparticle uptake into cells was dose-, time- and energy-dependent. Treatment with nanoparticles resulted in significantly higher cellular retention of drug than treatment with drug in solution. Cytotoxicity studies demonstrated that doxorubicin in nanoparticles resulted in significantly higher and more sustained cytotoxicity than drug in solution. Conclusions. AOT-alginate nanoparticles significantly enhance the cellular delivery of basic, water-soluble drugs. This translates into enhanced therapeutic efficacy for drugs like doxorubicin that have intracellular site of action. Based on these results, AOT-alginate nanoparticles appear to be suitable carriers for enhanced and sustained cellular delivery of basic, water-soluble drugs.

Original languageEnglish (US)
Pages (from-to)803-810
Number of pages8
JournalPharmaceutical research
Volume24
Issue number4
DOIs
StatePublished - Apr 1 2007

Keywords

  • Cellular drug delivery
  • Cytotoxicity
  • Endocytosis
  • Exocytosis
  • Sustained release

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