Biodegradable calcium phosphate nanoparticles as a new vehicle for delivery of a potential ocular hypotensive agent.
The purpose of this study was to determine the efficacy of a newly prepared formulation containing biodegradable calcium phosphate nanoparticles (CAP) and 7-hydroxy-2-dipropyl-aminotetralin (7-OH-DPAT) in pigmented and non-pigmented rabbits using the surrogate end points of intraocular pressure (IOP) and aqueous flow rate. IOP (mmHg) was measured by utilizing a manometrically calibrated Mentor pneumatonometer. Rates of aqueous humor flow were measured with a Fluorotron Master by estimating the dilution rate of fluorescein. In non-pigmented rabbits, the ocular hypotension induced by topical administration of 7-OH-DPAT (75 microg) with CAP (115 microg) was more pronounced and sustained than that of 7-OH-DPAT without CAP. Furthermore, IOP-lowering effects of topically administered 7-OH-DPAT (125 microg) alone were markedly diminished in pigmented rabbits compared to non-pigmented rabbits. However, topical application of 7-OH-DPAT formulated with CAP produced significant dose-related (37.5, 75, 125 microg) reductions of IOP accompanied by suppression of aqueous humor flow rates in pigmented rabbits. It is postulated that 7-OH-DPAT in vehicle without CAP binds to pigments in the anterior segment of the pigmented rabbit's eyes, and this binding limits the 7-OH-DPAT's action. Pretreatment with raclopride, a dopamine D2/D3 receptor antagonist, reduced the ocular hypotensive effect induced by 7-OH-DPAT in vehicle containing CAP thereby supporting the role for dopamine D2/D3 receptors in modulating IOP. It is concluded that CAP, as a delivery system, enhances activity by 7-OH-DPAT in pigmented rabbit eyes suggesting that CAP is potentially useful for achieving controlled and targeted drug delivery for treatment of ocular diseases.
Chu
Teh-Ching
TC
Department of Pharmacology and Toxicology, Morehouse School of Medicine, Atlanta, Georgia 30310-1495, USA. tc@msm.edu
He
Qing
Q
Potter
David E
DE
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000502:physiology; D001673:Biodegradation, Environmental; D002130:Calcium Phosphates / Q000378:metabolism*; D018491:Dopamine Agonists / Q000008:administration & dosage*; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005260:Female; D007429:Intraocular Pressure / Q000187:drug effects; D008297:Male; D036103:Nanotechnology; D009798:Ocular Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D010858:Pigmentation; D011817:Rabbits; D020891:Raclopride / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage*
D002130:Calcium Phosphates; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D013764:Tetrahydronaphthalenes; C485828:alpha-tricalcium phosphate; C485830:tetracalcium phosphate; D020891:Raclopride; C485838:calcium phosphate, monobasic, anhydrous; C020243:calcium phosphate; C485829:calcium phosphate, dibasic, anhydrous; C031349:7-hydroxy-2-N,N-dipropylaminotetralin