The delivery of therapeutics to the posterior segment of the eye is achieved by invasive procedures, including intravitreal injections and implants. The topically applied formulations would not permeate through different tissue barriers of the eye to reach the posterior segment. Here, we demonstrate the effectiveness of microneedle scleral patch in delivering the model molecule, triamcinolone acetonide, to the posterior segment of the eye. Microneedle scleral patch (MSP) and microneedle corneal patch (MCP) were fabricated through the micromolding technique using rapidly dissolvable polyvinylpyrrolidone. The patches containing 25 microneedles were characterized for physical and mechanical properties, drug loading and release behavior in vitro and ex vivo porcine eye globe model. The distribution of TA administered using MSP and MCP in different ocular tissues was evaluated in the rabbit eye model. The results showed that microneedles with 545 +/- 8 mu m length and 279 +/- 26 mu m width at the base in MSP penetrate the scleral membrane with the application of 0.35 +/- 0.06 N force. The needles dissolved within 60 s after insertion in the corneal and scleral tissue. The 5 min application of MSP showed a significantly (p < 0.05) greater TA disposition in the vitreous humor and choroid-retinal complex in excised porcine eye globe compared with MCP and TA nanosuspension eye drops. In rabbit model studies, the TA concentration was greatest in the choroid-retinal complex and sclera after administration through intravitreal injection and MSP, respectively. The TA disposition in the sclera was significantly (p < 0.05) greater after MSP application compared with intravitreal injection and MCP application for up to 24 h. MSP application provided a greater safety score compared with intravitreal injection. In conclusion, MSP can be developed as a minimally invasive drug delivery system to target the posterior segment of the eye.
机构:
Univ Barcelona, Dept Phys Chem, Fac Pharm, E-08028 Barcelona, SpainFernando Pessoa Univ, Fac Hlth Sci, P-4200150 Oporto, Portugal
Araujo, Joana
Nikolic, Sasha
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Univ Barcelona, Dept Phys Chem, Fac Pharm, E-08028 Barcelona, SpainFernando Pessoa Univ, Fac Hlth Sci, P-4200150 Oporto, Portugal
Nikolic, Sasha
Egea, Maria A.
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Univ Barcelona, Dept Phys Chem, Fac Pharm, E-08028 Barcelona, Spain
Univ Barcelona, Inst Nanosci & Nanotechnol, E-08028 Barcelona, SpainFernando Pessoa Univ, Fac Hlth Sci, P-4200150 Oporto, Portugal
Egea, Maria A.
Souto, Eliana B.
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Fernando Pessoa Univ, Fac Hlth Sci, P-4200150 Oporto, Portugal
Univ Tras Os Montes & Alto Douro IBB CGB UTAD, Inst Biotechnol & Bioengn, Ctr Genet & Biotechnol, P-5000801 Vila Real, PortugalFernando Pessoa Univ, Fac Hlth Sci, P-4200150 Oporto, Portugal
Souto, Eliana B.
Garcia, Maria L.
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Univ Barcelona, Dept Phys Chem, Fac Pharm, E-08028 Barcelona, Spain
Univ Barcelona, Inst Nanosci & Nanotechnol, E-08028 Barcelona, SpainFernando Pessoa Univ, Fac Hlth Sci, P-4200150 Oporto, Portugal
机构:
Univ Witwatersrand, Fac Hlth Sci, Sch Clin Med, Div Ophthalmol,Dept Neurosci, 7 York Rd Parktown, ZA-2193 Johannesburg, South AfricaUniv Witwatersrand, Fac Hlth Sci, Dept Pharm & Pharmacol, Sch Therapeut Sci,Wits Adv Drug Delivery Platform, 7 York Rd,Parktown, ZA-2193 Johannesburg, South Africa
Ally, Naseer
Choonara, Yahya Essop
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Univ Witwatersrand, Fac Hlth Sci, Dept Pharm & Pharmacol, Sch Therapeut Sci,Wits Adv Drug Delivery Platform, 7 York Rd,Parktown, ZA-2193 Johannesburg, South AfricaUniv Witwatersrand, Fac Hlth Sci, Dept Pharm & Pharmacol, Sch Therapeut Sci,Wits Adv Drug Delivery Platform, 7 York Rd,Parktown, ZA-2193 Johannesburg, South Africa
机构:
Tel Aviv Univ, Sackler Fac Med, Tel Aviv Med Ctr, Dept Ophthalmol, IL-69978 Tel Aviv, IsraelUniv Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USA
Fischer, Naomi
Narayanan, Raja
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LV Prasad Eye Inst, Hyderabad, Andhra Pradesh, IndiaUniv Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USA
Narayanan, Raja
Loewenstein, Anat
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Tel Aviv Univ, Sackler Fac Med, Tel Aviv Med Ctr, Dept Ophthalmol, IL-69978 Tel Aviv, IsraelUniv Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USA
Loewenstein, Anat
Kuppermann, Baruch D.
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Univ Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USAUniv Calif Irvine, Dept Ophthalmol, Gavin Herbert Eye Inst, Irvine, CA 92697 USA