Abstract
Purpose :
While the use of anti-VEGF agents intraocular injection is a key component in the management of AMD and diabetic retinopathy, the risk associated with repetitive intraocular injections is not ideal. We propose the use of optically-active nanocarriers (NCs) and laser-stimulated drug release as a safe and effective alternative for controlled drug delivery. We tested the hypothesis that optical stimulation of Avastin-loaded NCs may be used for incremental drug delivery via photoacoustic pressure wave generation and absorption within the NC matrix.
Methods :
Four types of nanocarriers (NC) of less than 500 nm in size were synthesized: (1) chitosan only (CS); (2) chitosan plus Lucifer Yellow (CS-LY); (3) chitosan plus fluorescein (CS-F); and (4) chitosan plus gold nanoparticles (CS-Au). During synthesis, the NC were loaded using a concentration of 3 mg/ml Avastin. Subsequently, non-encapsulated and unbound Avastin was washed away. The loaded NC were exposed to a tunable laser (Ekspla model NT342B OPO; pulse duration of 5 nsec and 20 Hz repetition rate) with a delivered energy of 1 or 5 mJ and a wavelength of 428, 460, or 532 nm, depending on the optical absorption of the NC. Release of Avastin into the supernatant of each NC sample was measured by HPLC carried out with a size exclusion column (Shodex KW-803) and UV detection at 239 nm. Statistical analysis of the results was by non-parametric Wilcoxon rank order test.
Results :
All of the NC types successfully incorporated Avastin and exhibited baseline release of the agent (mean±s.d. µg/ml, # of samples): CS: 105.2±203.5, n=11; CS-LY: 88.8±166.3, n=10; CS-F: 79.1±136.3, n=10; and CS-Au: 64.7±120.2, n=11. Laser irradiation significantly enhanced the release only in the CS and CS-LY groups: mean increase in release was 4.1% and 6.0%, respectively (p≤0.05).
Conclusions :
The present results indicate that laser-stimulated release of Avastin from NCs via photoacoustic pressure wave generation is possible and that the success of optically stimulated release depends greatly on NC matrix composition. Further refinement of the NC matrix is needed to reduce baseline drug dissolution as well as augment laser-stimulated Avastin release. While further study is needed, we envision an optimized, multi-dose loaded matrix that, once delivered to the ocular media, may serve as a robust source for noninvasive on-demand drug delivery.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.