Controlled release of photoswitch drugs by degradable polymer microspheres

J Drug Target. 2015;23(7-8):710-5. doi: 10.3109/1061186X.2015.1060978.


Background: QAQ (quaternary ammonium-azobenzene-quaternary ammonium) and DENAQ (diethylamine-azobenzene-quaternary ammonium) are synthetic photoswitch compounds that change conformation in response to light, altering current flow through voltage-gated ion channels in neurons. These compounds are drug candidates for restoring light sensitivity in degenerative blinding diseases, such as age-related macular degeneration (AMD).

Purpose: However, these photoswitch compounds are cleared from the eye within several days, they must be administered through repeated intravitreal injections. Therefore, we are investigating local, sustained delivery formulations to constantly replenish these molecules and have the potential to restore sight.

Methods: Here, we encapsulate QAQ and DENAQ into several molecular weights of poly(lactic-co-glycolic) acid (PLGA) through an emulsion technique to assess the viability of delivering the compounds in their therapeutic window over many weeks. We characterize the loading efficiency, release profile and bioactivity of the compounds after encapsulation.

Results: A very small burst release was observed for all of the formulations with the majority being delivered over the following two months. The lowest molecular weight PLGA led to the highest loading and most linear delivery for both QAQ and DENAQ. Bioactivity was retained for both compounds across the polymers.

Conclusion: These results present encapsulation into polymers by emulsion as a viable option for controlled release of QAQ and DENAQ.

Keywords: DENAQ; PLA; PLGA; QAQ; eye; local delivery; ocular delivery; sustained delivery.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Azo Compounds / administration & dosage*
  • Azo Compounds / chemistry
  • Delayed-Action Preparations
  • Drug Carriers
  • Drug Delivery Systems*
  • Drug Liberation
  • Emulsions
  • Lactic Acid / chemistry
  • Microspheres
  • Molecular Weight
  • Polyglycolic Acid / chemistry
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polymers / chemistry*
  • Quaternary Ammonium Compounds / administration & dosage*
  • Quaternary Ammonium Compounds / chemistry


  • Azo Compounds
  • DENAQ compound
  • Delayed-Action Preparations
  • Drug Carriers
  • Emulsions
  • Polymers
  • QAQ compound
  • Quaternary Ammonium Compounds
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid