Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery

De, T. K.; Rodman, D. J.; Holm, Bruce A.; Prasad, Paras N.; Bergey, Earl J.

doi:10.1080/0265204031000093591

Cited by 13 publications

(10 citation statements)

References 49 publications

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“…Many polymers ranging from natural, semi synthetic, synthetic and biodegradable have been investigated in the preparation of ocular nanoparticles. Polymers investigated are bovine serum albumin (5), poly(lactide-co-glycolide) (6)(7)(8), chitosan (9)(10)(11)(12), polymethacrylates (13), poly epsiloncaprolactone (14,15) and poly carboxylic acid (16,17).…”

Section: Introductionmentioning

confidence: 99%

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation, Optimization, In Vitro and In Vivo Evaluation

Bhagav

Upadhyay

Chandran³

2011

AAPS PharmSciTech

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Abstract. In the present study, an effort was made to design prolonged release Eudragit nanoparticles of brimonidine tartrate by double emulsion-solvent evaporation technique for the treatment of open-angle glaucoma. The effect of various formulation variables like initial drug amount, lecithin proportion, phase volume and pH, secondary emulsifier and polymer proportion were studied. Various process variables like energy and duration of emulsification, lyophilization on the characteristics of nanoparticles and in vitro drug release profile were studied. The selected formulations were subjected to in vivo intraocular pressure-lowering efficacy studies by administering aqueous dispersion of nanoparticles into the lower cul de sac of glaucomatous rabbits. The prepared Eudragit-based nanoparticles were found to have narrow particle size range and improved drug loading. The investigated process and formulation variables found to have significant effect on the particle size, drug loading and entrapment efficiency, and in vitro drug release profile of nanoparticles. The selected formulations upon in vivo ocular irritability and tolerability tests were found to be well tolerated with no signs of irritation. In vivo pharmacodynamic efficacy studies revealed that the selected nanoparticle formulations significantly improved the therapy as area under the ΔIOP vs. time curve [AUC (ΔIOP vs.t) ] showed several fold increase in intensity and duration of intraocular pressure (IOP) decrease. All the selected nanoparticle formulations were found to prolong the drug release in vitro and prolong IOP reduction efficacy in vivo, thus rendering them as a potential carrier in developing improved drug delivery systems for the treatment of glaucoma.

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Section: Introductionmentioning

confidence: 99%

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation, Optimization, In Vitro and In Vivo Evaluation

Bhagav

Upadhyay

Chandran³

2011

AAPS PharmSciTech

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“…Topical drop administration of ophthalmic drugs in aqueous solutions results in extensive drug loss due to tear fluid and eyelid dynamics (De et al, 2003;Hoffman, 2001a, 2001b). Major problem in ocular delivery is to maintain an adequate concentration of the therapeutic agent in the precorneal area.…”

Section: Ocular Applications Of Nanoparticulate Drug-delivery Systemmentioning

confidence: 99%

Nanoparticles: a boon for modernisation of drug delivery: a review

Khan

Gowda

2011

IJNP

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In the medical field, the active ingredient is in the form of solid particles for 90% of all medicines. Because of development in nanotechnology, it is now possible to produce drug nanoparticles that can be utilised in a variety of innovative ways according to the need. From few decades, there had been considerable interest in area of nanotechnology and many works have been done in order to deliver drugs using particulate delivery systems (nanoparticles) as carriers for small and large molecules. Development of nanoparticles arose in response to vast and broad medical needs, common to a number of therapeutic areas and targets. The potential advantages of nanoparticles as oral drug carriers are enhancement of bioavailability, delivery of vaccine antigens to the gut-associated lymphoid tissues (GALT), controlled release, and reduction of the gastrointestinal irritation caused by drugs. Beside this nanoparticles also offer other route of administrations. Various polymers have been used in the formulation of nanoparticles for drug delivery research to increase therapeutic benefit, while minimising side effects. This review article laid emphasis on various aspects of nanoparticles, their uptake, formulation, characterisation and applications of nanoparticles approach in delivery of drugs molecules and genes. He has worked on microspheres, microparticles, nanoparticles, porous pellets and controlled drug delivery systems.

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“…But perhaps the most attractive method to improve eye drop adherence is through the use of controlled-release drug delivery systems that obviate the need for the patient to take eye drops at all. While brimonidine-loaded drug delivery systems for the management of glaucoma have been studied before [19–22], we seek to determine the efficacy of a targeted controlled-release system delivered using a microneedle adjacent to brimonidine’s site of action in the ciliary body.…”

Section: Introductionmentioning

confidence: 99%

“…Brimonidine was chosen because it is an FDA-approved IOP-lowering agent currently prescribed to glaucoma patients [12,13,40] and is pharmacologically active in the rabbit [19–22,41]. Due to increased bioavailability, a microneedle injection into the supraciliary space should reduce the dose needed, compared with topical eye drops, thereby allowing a relatively small injection to contain sufficient drug for extended therapy.…”

Section: Introductionmentioning

confidence: 99%

Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma

Chiang

Kim

Doty

et al. 2016

Journal of Controlled Release

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Although effective drugs that lower intraocular pressure (IOP) in the management of glaucoma exist, their efficacy is limited by poor patient adherence to the prescribed eye drop regimen. To replace the need for eye drops, in this study we tested the hypothesis that IOP can be reduced for one month after a single targeted injection using a microneedle for administration of a glaucoma medication (i.e., brimonidine) formulated for sustained release in the supraciliary space of the eye adjacent to the drug’s site of action at the ciliary body. To test this hypothesis, brimonidine-loaded microspheres were formulated using poly(lactic acid) (PLA) to release brimonidine at a constant rate for 35 days and microneedles were designed to penetrate through the sclera, without penetrating into the choroid/retina, in order to target injection into the supraciliary space. A single administration of these microspheres using a hollow microneedle was performed in the eye of New Zealand White rabbits and was found to reduce IOP initially by 6 mm Hg and then by progressively smaller amounts for more than one month. All administrations were well tolerated without significant adverse events, although histological examination showed a foreign-body reaction to the microspheres. This study demonstrates, for the first time, that the highly-targeted delivery of brimonidine-loaded microspheres into the supraciliary space using a microneedle is able to reduce IOP for one month as an alternative to daily eye drops.

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Brimonidine formulation in polyacrylic acid nanoparticles for ophthalmic delivery

Cited by 13 publications

References 49 publications

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation, Optimization, In Vitro and In Vivo Evaluation

Brimonidine Tartrate–Eudragit Long-Acting Nanoparticles: Formulation, Optimization, In Vitro and In Vivo Evaluation

Nanoparticles: a boon for modernisation of drug delivery: a review

Sustained reduction of intraocular pressure by supraciliary delivery of brimonidine-loaded poly(lactic acid) microspheres for the treatment of glaucoma

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