Novel Strategies for Anterior Segment Ocular Drug Delivery

Cholkar, Kishore; Patel, Sulabh; Vadlapudi, Aswani Dutt; Mitra, Ashim K.

doi:10.1089/jop.2012.0200

Cited by 145 publications

(113 citation statements)

References 138 publications

(116 reference statements)

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“…After topical ophthalmic drop instillation into pre-corneal pocket, formulations/solutions are rapidly cleared (within 5 to 10 min) (6,42). Therefore, to determine the cytotoxic effect of MNF upon long-time exposure to ocular tissues, LDH and cell proliferation assay were performed for 1 and 2 h of exposure.…”

Section: Cytotoxicity Studiesmentioning

confidence: 99%

“…Further, this new vasculature causes capillaries to leak causing blood and fluid accumulation in the retinal layers. During neovascularization, vascular endothelial growth factor (VEGF) is upregulated (6). Increased production of VEGF is induced by multiple cellular pathways: (i) hypoxia and (ii) pro-inflammatory cytokines such as TNF-α and β2 (7,8).…”

Section: Introductionmentioning

confidence: 99%

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Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery

et al. 2014

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Abstract. The objective of this study was to develop a clear, aqueous rapamycin-loaded mixed nanomicellar formulations (MNFs) for the back-of-the-eye delivery. MNF of rapamycin (0.2%) was prepared with vitamin E tocopherol polyethylene glycol succinate (TPGS) (Vit E TPGS) and octoxynol-40 (Oc-40) as polymeric matrix. MNF was characterized by various parameters such as size, charge, shape, and viscosity. Proton nuclear magnetic resonance ( 1 H NMR) was used to identify unentrapped rapamycin in MNF. Cytotoxicity was evaluated in human retinal pigment epithelial (D407) and rabbit primary corneal epithelial cells (rPCECs). In vivo posterior ocular rapamycin distribution studies were conducted in male New Zealand white rabbits. The optimized MNF has excellent rapamycin entrapment and loading efficiency. The average size of MNF was 10.98±0.089 and 10.84±0.11 nm for blank and rapamycin-loaded MNF, respectively. TEM analysis revealed that nanomicelles are spherical in shape. Absence of free rapamycin in the MNF was confirmed by 1 H NMR studies. Neither placebo nor rapamycin-loaded MNF produced cytotoxicity on D407 and rPCECs indicating formulations are tolerable. In vivo studies demonstrated a very high rapamycin concentration in retina-choroid (362.35±56.17 ng/g tissue). No drug was identified in the vitreous humor indicating the sequestration of rapamycin in lipoidal retinal tissues. In summary, a clear, aqueous MNF comprising of Vit E TPGS and Oc-40 loaded with rapamycin was successfully developed. Back-of-the-eye tissue distribution studies demonstrated a very high rapamycin levels in retina-choroid (place of drug action) with a negligible drug partitioning into vitreous humor.

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Section: Cytotoxicity Studiesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery

et al. 2014

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“…CMC is a critical factor that regulates premature release of drug due to tear dilution after topical drop administration. Of the total volume applied, only 20% of the formulation is available for absorption (34). The applied formulation occupies the space in precorneal pocket by replacing lacrimal fluid.…”

Section: Critical Micellar Concentrationmentioning

confidence: 99%

Optimization of Dexamethasone Mixed Nanomicellar Formulation

et al. 2014

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Abstract. The purpose of this study was to develop a clear aqueous mixed nanomicellar formulation (MNF) of dexamethasone utilizing both D-α-tocopherol polyethylene glycol-1000 succinate (Vit E TPGS) and . In this study, Vit E TPGS and Oc-40 are independent variables. Formulations were prepared following solvent evaporation method. A three level full-factorial design was applied to optimize the formulation based on entrapment efficiency, size, and polydispersity index (PDI). A specific blend of Vit E TPGS and Oc-40 at a particular wt% ratio (4.5:2.0) produced excellent drug entrapment, loading, small mixed nanomicellar size and narrow PDI. Solubility of DEX in MNF is improved by~6.3-fold relative to normal aqueous solubility. Critical micellar concentration (CMC) for blend of polymers (4.5:2.0) was found to be lower (0.012 wt%) than the individual polymers (Vit E TPGS (0.025 wt%) and Oc-40 (0.107 wt%)). No significant effect on mixed nanomicellar size and PDI with one-factor or multifactor interactions was observed. Qualitative 1 H NMR studies confirmed absence of free drug in the outer aqueous MNF medium. MNF appeared to be highly stable. Cytotoxicity studies on rabbit primary corneal epithelial cells did not indicate any toxicity suggesting MNF of dexamethasone is safe and suitable for human topical ocular drops after further in vivo evaluations.

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“…Addition of viscosity enhancing agent or mucoadhesive polymers to the formulation increases the contact time of the drug with the ocular surface, thereby improving its bioavailability in the anterior ocular compartments. Commonly used viscosity enhancing agents are polyvinylpyrrolidone and hydroxypropyl methylcellulose (HPMC) [38].…”

Section: General Considerations For Designing Ocular Drug Delivery Fomentioning

confidence: 99%

Topical Drug Delivery for Effective Treatment of Bacterial Infections of the Anterior Segment of the Eye

El-Bary

Ibrahim

Haza'a

2018

Asian J Pharm Clin Res

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Anterior parts of the eye are susceptible to infections caused by different bacterial species. The use of suitable therapeutic measures in case of ocular infections can be sight saving. The appropriate therapy depends on selecting the right antibacterial as well as an efficient drug delivery system. Despite their accessibility, topical delivery of the selected antibiotic into the anterior ocular parts is still a challenging issue due to the complex nature of the eye. Ocular therapy would be significantly improved by modifying the physicochemical properties of the drug and by prolonging its pre-corneal residence time. This review will help pharmaceutical formulators to identify different parts of the eye and the corresponding bacterial infections, ocular barriers to drug delivery, and general consideration when formulating ocular drug delivery systems for the treatment of eye infections.

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Novel Strategies for Anterior Segment Ocular Drug Delivery

Cited by 145 publications

References 138 publications

Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery

Nanomicellar Topical Aqueous Drop Formulation of Rapamycin for Back-of-the-Eye Delivery

Optimization of Dexamethasone Mixed Nanomicellar Formulation

Topical Drug Delivery for Effective Treatment of Bacterial Infections of the Anterior Segment of the Eye

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