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1 General aspects (0)   1.1 Epidemiology (15)   1.2 Population genetics (0)   1.3 Pathogenesis (4)   1.4 Quality of life (8)   1.5 Glaucomas as cause of blindness (11)   1.6 Prevention and screening (4) 2 Anatomical structures in glaucoma (0)   2.1 Conjunctiva (3)   2.2 Cornea (20)   2.3 Sclera (8)   2.4 Anterior chamber angle (5)   2.5 Meshwork (0)     2.5.1 Trabecular meshwork (18)     2.5.2 Schlemms canal (3)     2.5.3 Scleral outlet channels (0)   2.6 Aqueous humor dynamics (0)     2.6.1 Production (1)     2.6.2 Outflow (0)       2.6.2.1 Trabecular meshwork (4)       2.6.2.2 Uveoscleral (0)     2.6.3 Compostion (3)   2.7 Episcleral veins and venous pressure (0)   2.8 Iris (6)   2.9 Ciliary body (2)   2.10 Lens (1)   2.11 Vitreous body (0)   2.12 Choroid, peripapillary choroid, peripapillary atrophy (9)   2.13 Retina and retinal nerve fibre layer (29)   2.14 Optic disc (28)   2.15 Optic nerve (1)   2.16 Chiasma and retrochiasmal central nervous system (6)   2.17 Stem cells (3)   2.20 Other (0) 3 Laboratory methods (0)   3.1 Microscopy (1)   3.2 Electron microscopy (1)   3.3 Immunohistochemistry (0)   3.4 Molecular genetics (0)     3.4.1 Linkage studies (0)     3.4.2 Gene studies (20)   3.5 Molecular biology incl. SiRNA (14)   3.6 Cellular biology (27)   3.7 Biochemistry (8)   3.8 Pharmacology (12)   3.9 Pathophysiology (4)   3.10 Immunobiology (5)   3.11 Pharmacogenetics (0)   3.12 Proteomics (1)   3.13 In vivo imaging (0)     3.13.1 Laser Scanning (0)       3.13.1.1 Confocal Scanning Laser Ophthalmoscopy (0)       3.13.1.2 Confocal Scanning Laser Polarimetry (0)     3.13.2 Optical Coherence Tomography (0)       3.13.2.1 Anterior Segment (1)       3.13.2.2 Posterior Segment (0)     3.13.3 RGC Imaging (0)     3.13.4 Other (0)   3.20 Other (0) 4 Tissue culture of ocular cells (0) 5 Experimental glaucoma; animal models (0)   5.1 Rodent (17)   5.2 Primates (3)   5.3 Other (9) 6 Clinical examination methods (0)   6.1 Intraocular pressure measurement; factors affecting IOP (0)     6.1.1 Devices, techniques (6)     6.1.2 Fluctuation, circadian rhythms (2)     6.1.3 Factors affecting IOP (17)   6.2 Tonography, aqueous flow measurement (see also 2.6) (1)   6.3 Biomicroscopy (slitlamp) (0)     6.3.1 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8 Refractive errors in relation to glaucoma (0)   8.1 Myopia (3)   8.2 Hypermetropia (0)   8.3 Contact lenses (0)   8.4 Refractive surgical procedures (0)   8.5 Other (0) 9 Clinical forms of glaucomas (0)   9.1 Developmental glaucomas (0)     9.1.1 Congenital glaucoma, Buphthalmos (9)     9.1.2 Juvenile glaucoma (6)     9.1.3 Syndromes of Axenfeld, Rieger, Peters, aniridia (1)     9.1.4 Other (0)   9.2 Primary open angle glaucomas (0)     9.2.1 Ocular hypertension (1)     9.2.2 Other risk factors for glaucoma (14)     9.2.3 Open angle glaucoma with elevated IOP (2)     9.2.4 Normal pressure glaucoma (8)   9.3 Primary angle closure glaucomas (0)     9.3.1 Acute primary angle closure glaucoma (pupillary block) (8)     9.3.2 Chronic primary angle closure glaucoma (pupillary block) (3)     9.3.3 Plateau iris syndrome (1)     9.3.4 Primary angle closure suspect (1)     9.3.5 Primary angle closure (6)     9.3.10 Other (0)   9.4 Glaucomas associated with other ocular and systemic disorders 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associated with intraocular tumors (8)     9.4.9 Glaucomas associated with elevated episcleral venous pressure (0)       9.4.10 Glaucomas associated with hemorrhage (3)     9.4.11 Glaucomas following intraocular surgery (0)       9.4.11.1 Ciliary block (malignant) glaucoma (2)       9.4.11.2 Glaucomas in aphakia and pseudophakia (9)       9.4.11.3 Epithelial, fibrous, and endothelial proliferation (0)       9.4.11.4 Glaucomas associated with corneal surgery (8)       9.4.11.5 Glaucomas associated with vitreoretinal surgery (9)     9.4.15 Glaucoma in relation to systemic disease (30)     9.4.20 Other (0) 10 Differential diagnosis e.g. anterior and posterior ischemic optic neuropathy (1) 11 Medical treatment (0)   11.1 General management, indication (1)   11.2 Cholinergic drugs (1)   11.3 Adrenergic drugs (0)     11.3.1 Epinephrine (0)     11.3.2 Thymoxamine, dapiprazole (0)     11.3.3 Apraclonidine, brimonidine (0)     11.3.4 Betablocker (4)     11.3.5 Other (0)   11.4 Prostaglandins 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    12.8.1 Without tube implant (11)     12.8.2 With tube implant or other drainage devices (15)     12.8.3 Non-perforating (8)     12.8.4 Using laser (0)     12.8.5 Other (0)     12.8.10 Woundhealing antifibrosis (12)     12.8.11 Complications, endophthalmitis (7)   12.9 Trabeculotomy, goniotomy (6)   12.10 Cyclodestruction (5)   12.11 Cyclodialysis (1)   12.12 Cataract extraction (0)     12.12.1 Intracapsular (0)     12.12.2 Extracapsular (0)     12.12.3 Phacoemulsification (5)   12.14 Combined cataract extraction and glaucoma surgery (0)     12.14.1 Intracapsular (0)     12.14.2 Extracapsular (0)     12.14.3 Phacoemulsification (7)   12.15 Capsulotomy (0)   12.16 Vitrectomy (0)   12.17 Anesthesia (1)   12.20 Other (0) 13 Therapeutic prognosis and outcome (0)   13.1 Prognostic factors (0)   13.2 Outcome (0)     13.2.1 IOP (3)     13.2.2 Visual field (1)       13.2.2.1 Progression (0)       13.2.2.2 Improvement (0)     13.2.3 Other (1) 14 Costing studies; pharmacoeconomics (0) 15 Miscellaneous (17)

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Abstract #56088 Published in IGR 16-1

Sustained drug release in nanomedicine: a long-acting nanocarrier-based formulation for glaucoma

Natarajan JV; Darwitan A; Barathi VA; Ang M; Htoon HM; Boey F; Tam KC; Wong TT; Venkatraman SS
ACS nano 2014; 8: 419-429

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Therapeutic nanomedicine has concentrated mostly on anticancer therapy by making use of the nanosize for targeted therapy. Such nanocarriers are not expected to have sustained release of the bioactive molecule beyond a few days. There are other conditions where patients can benefit from sustained duration of action following a single instillation, but achieving this has been difficult in nanosized carriers. An important prerequisite for sustained delivery over several months is to have sufficiently high drug loading, without disruption or changes to the shape of the nanocarriers. Here we report on successful development of a drug-encapsulated nanocarrier for reducing intraocular pressure in a diseased nonhuman primate model and explain why it has been possible to achieve sustained action in vivo. The drug is a prostaglandin derivative, latanoprost, while the carrier is a nanosized unilamellar vesicle. The mechanistic details of this unique drug-nanocarrier combination were elucidated by isothermal titration calorimetry. We show, using Cryo-TEM and dynamic light scattering, that the spherical shape of the liposomes is conserved even at the highest loading of latanoprost and that specific molecular interactions between the drug and the lipid are the reasons behind improved stability and sustained release. The in vivo results clearly attest to sustained efficacy of lowering the intraocular pressure for 120 days, making this an excellent candidate to be the first truly sustained-release nanomedicine product. The mechanistic details we have uncovered should enable development of similar systems for other conditions where sustained release from nanocarriers is desired.

Full article

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Classification:

11.16 Vehicles, delivery systems, pharmacokinetics, formulation (Part of: 11 Medical treatment)

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