Formation of Drug-Participating Catanionic Aggregates for Extended Delivery of Non-Steroidal Anti-Inflammatory Drugs from Contact Lenses

Biomolecules. 2019 Oct 10;9(10):593. doi: 10.3390/biom9100593.

Abstract

This paper focuses on extending drug release duration from contact lenses by incorporating catanionic aggregates. The aggregates consist of a long-chain cationic surfactant, i.e., cetalkonium chloride (CKC), and an oppositely charged anti-inflammatory amphiphilic drug. We studied three non-steroidal anti-inflammatory (NSAID) drugs with different octanol-water partition coefficients; diclofenac sodium (DFNa), flurbiprofen sodium (FBNa), and naproxen sodium (NPNa). Confirmation of catanionic aggregate formation in solution was determined by steady and dynamic shear rheology measurements. We observed the increased viscosity, shear thinning, and viscoelastic behavior characteristic of wormlike micelles; the rheological data are reasonably well described using a Maxwellian fluid model with a single relaxation time. In vitro release experiments demonstrated that the extension in the drug release time is dependent on the ability of a drug to form viscoelastic catanionic aggregates. Such aggregates retard the diffusive transport of drug molecules from the contact lenses. Our study revealed that the release kinetics depends on the CKC concentration and the alkyl chain length of the cationic surfactant. We demonstrated that more hydrophobic drugs such as diclofenac sodium show a more extended release than less hydrophobic drugs such as naproxen sodium.

Keywords: Maxwell model; NSAID; aggregates; cationic surfactant; contact lenses; controlled release; drug delivery; hydrogel; rheology; wormlike micelles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents, Non-Steroidal / chemistry*
  • Cations / chemistry
  • Contact Lenses*
  • Diclofenac / chemistry
  • Diffusion
  • Drug Delivery Systems*
  • Drug Liberation
  • Fatty Alcohols / chemistry*
  • Flurbiprofen / chemistry
  • Hydrophobic and Hydrophilic Interactions
  • Kinetics
  • Naproxen / chemistry
  • Quaternary Ammonium Compounds / chemistry*
  • Surface-Active Agents / chemistry*
  • Viscosity

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Cations
  • Fatty Alcohols
  • Quaternary Ammonium Compounds
  • Surface-Active Agents
  • Diclofenac
  • Naproxen
  • Flurbiprofen
  • cetalkonium chloride