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R.V. Dorjahn, J.H. Bertera; Retinal and CNS drug delivery enabled by micro volume projector method through the ocular route. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):5051.
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Purpose: To describe a micro volume projector for delivering micro droplets of drug solutions to the ocular surface for absorption to the posterior segment and central nervous system (CNS). Besides absorption through conjunctiva, topically applied solutions drain rapidly into puncta, canaliculi, and arrive at nasal mucosa. Conjunctival absorption and rapid drainage that ordinarily contributes to side–effects and drug loss with some ophthalmic medications may be useful for delivering drugs to retina and CNS. Koevary (2003;2002) recently demonstrated that relatively high molecular weight drugs such as insulin may be passed into retina and optic nerve after topical application, bypassing the blood brain barrier. Methods: A micro volume projector powered by programmable electronics mounted on eyeglass frames is described that delivers nanoliter range drops and submicroliter doses to ocular surfaces. Typical eyedrop volume is 30 microliters and normally drains rapidly from ocular surfaces through puncta (90% in 3 minutes). The same volume can be dispensed in microdoses over many minutes or pulsively. For conjunctival absorption, frequent microdoses can be programmed to better match slow drug absorption (e.g. 0.5 microliter per minute, for 300 minutes). Precision "pulse delivery" can program can deliver drug to nasal mucosa, by promoting fast drainage to puncta (e.g. 10 microliters every 5 minutes). Results: Calculations show that an adaptive dose pattern has the potential for strategic drug targeting. The method has the precision for maximizing drug absorption to conjunctiva with long duration low doses. And, it can also push fluids for rapid transfer to nasal mucosa. For example, the precorneal, or mucosal, residence time can be increased from 3 minutes for a single drop to 300 minutes or more. Comparisons with alternative drug delivery methods for retina and CNS indicate some advantages for the micro volume projector method. Conclusions:The prolonged strategic microdosing with the wearable droplet projector may be sufficient to deliver therapeutic drug concentrations to retina or CNS, especially for larger molecules due to their slow absorption. Drug developers may use the method to deliver putative drugs before an effective other vehicle can be developed for animal or clinical testing, thus improving productivity in drug discovery and drug testing. The micro volume method may also have potential for treating CNS diseases such as tumors, stroke, Alzheimer’s and AIDS–related complications by bypassing the blood brain barrier.
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