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

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.

Optimization of dexamethasone mixed nanomicellar formulation.

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 octoxynol-40 (Oc-40). In this study, Vit E TPGS and Oc-40 are independent variables. Formulations were prepared following solvent evaporation method.

Pharmacokinetic studies and LC-MS/MS method development of ganciclovir and dipeptide monoester prodrugs in Sprague Dawley rats.

Ganciclovir (GCV) is utilized as an anti-herpetic agent. Reports from our laboratory have suggested that dipeptide ester prodrugs of GCV exhibit high affinity towards the oligopeptide transporter hPEPT1 and therefore seem to be promising candidates for the treatment of oral herpes virus infections. In this study, we have examined the bio-availability of a dipeptide prodrug of GCV after oral administration in jugular cannulated Sprague-Dawley rats.

Bioanalytical method validation of rapamycin in ocular matrix by QTRAP LC-MS/MS: application to rabbit anterior tissue distribution by topical administration of rapamycin nanomicellar formulation.

A novel, fast and sensitive 3200 QTRAP LC-MS/MS method was validated for rapamycin analysis in the rabbit eye following 0.2% administration of nanomicellar eye drop formulation. The LC-MS/MS technique was developed with electrospray ionization (ESI) in positive mode.

Ocular microdialysis: a continuous sampling technique to study pharmacokinetics and pharmacodynamics in the eye.

The unique anatomy and physiology of the eye present many challenges to the successful development and delivery of ophthalmic drugs. Any therapeutic strategy developed to control the progression of anterior and posterior segment diseases requires continuous monitoring of effective drug concentrations in the relevant ocular tissues and fluids. Ocular microdialysis has gained popularity in recent years due to its ability to continuously monitor drug concentrations and substantially reduce the number of animals needed.

Enhanced corneal absorption of erythromycin by modulating P-glycoprotein and MRP mediated efflux with corticosteroids.

Purpose: The objectives were (i) to test in vivo functional activity of MRP2 on rabbit corneal epithelium and (ii) to evaluate modulation of P-gp and MRP2 mediated efflux of erythromycin when co-administered with corticosteroids.

Methods: Cultured rabbit primary corneal epithelial cells (rPCECs) was employed as an in vitro model for rabbit cornea. Cellular accumulation and bi-directional transport studies were conducted across Madin-Darby Canine Kidney (MDCK) cells overexpressing MDR1 and MRP2 proteins to delineate transporter specific interaction of steroids.

Ocular pharmacokinetics of acyclovir amino acid ester prodrugs in the anterior chamber: evaluation of their utility in treating ocular HSV infections.

Purpose: To evaluate in vivo corneal absorption of the amino acid prodrugs of acyclovir (ACV) using a topical well model and microdialysis in rabbits.

Methods: Stability of L-alanine-ACV (AACV), L-serine-ACV (SACV), L-isoleucine-ACV (IACV), gamma-glutamate-ACV (EACV) and L-valine-ACV (VACV) prodrugs was evaluated in various ocular tissues. Dose-dependent toxicity of these prodrugs was also examined in rabbit primary corneal epithelial cell culture (rPCEC) using 96-well based cell proliferation assay.

Novel approaches to retinal drug delivery.

Research into treatment modalities affecting vision is rapidly progressing due to the high incidence of diseases such as diabetic macular edema, proliferative vitreoretinopathy, wet and dry age-related macular degeneration and cytomegalovirus retinitis. The unique anatomy and physiology of eye offers many challenges to developing effective retinal drug delivery systems. Historically, drugs have been administered to the eye as liquid drops instilled in the cul-de-sac.

Corneal absorption and anterior chamber pharmacokinetics of dipeptide monoester prodrugs of ganciclovir (GCV): in vivo comparative evaluation of these prodrugs with Val-GCV and GCV in rabbits.

Aim: The overall aim of this study was to evaluate the corneal absorption of dipeptide monoester prodrugs of ganciclovir (GCV) and compare these results with L-valine-GCV and GCV. Another aim was to evaluate the pharmacokinetics of these prodrugs in aqueous humor.

Methods: A well was placed on the cornea of anesthetized New Zealand albino rabbits with linear probes implanted in the aqueous humor.

Identification and functional expression of a carrier-mediated riboflavin transport system on rabbit corneal epithelium.

Purpose: To investigate the functional expression of a carrier-mediated transport mechanism for riboflavin (vitamin B2) across cultured rabbit primary corneal epithelial cells (rPCECs) and intact rabbit cornea. The secondary objective was to understand the physiological significance behind the presence of such a transport system for riboflavin on the apical side of the corneal epithelium.

Methods: rPCECs and freshly excised rabbit corneas were selected as in vitro and ex vivo models, respectively.

In vivo ocular pharmacokinetics of acyclovir dipeptide ester prodrugs by microdialysis in rabbits.

In vivo corneal absorption of the dipeptide prodrugs of acyclovir (ACV) was evaluated using microdialysis in rabbits. A corneal well was placed on the cornea of the anesthetized New Zealand White rabbits with implanted linear probes into the aqueous humor. Two hundred microliters of a 1% solution of L-valine-ACV (VACV), glycine-valine-ACV (GVACV), valine-valine-ACV (VVACV), and valine-tyrosine-ACV (VYACV) was placed in the corneal well and was allowed to diffuse for a period of 2 h, following which the drug solution was aspirated and well removed.

Identification of a Na+-dependent cationic and neutral amino acid transporter, B(0,+), in human and rabbit cornea.

The purpose of this study was to identify and functionally characterize an active transport system for L-arginine on rabbit corneal epithelium and human cornea and study its interaction with the amino acid ester prodrugs of acyclovir (Anand, B. S.; Mitra, A.

Functional activity of a monocarboxylate transporter, MCT1, in the human retinal pigmented epithelium cell line, ARPE-19.

The purpose of this study was to identify and characterize the functional activity of monocarboxylic acid transporter 1 (MCT1) on the human retinal pigmented epithelium (RPE) cell line, ARPE-19, and to evaluate whether the cell line can function as an in vitro screening tool for intravitreally administered drugs/prodrugs targeted to the MCT1 expressed in RPE. Uptake studies were carried out at 37 degrees C, for 30 s, with ARPE-19 cells. [(14)C]l-Lactic acid was selected as a substrate for this transporter.

Pharmacokinetics of erythromycin in rabbit corneas after single-dose infusion: role of P-glycoprotein as a barrier to in vivo ocular drug absorption.

Efflux pump like P-glycoprotein (P-gp) is known to be a major barrier to drug delivery. Functional P-glycoprotein has been recently identified in cornea and corneal cell lines. Thus, it is probable that P-glycoprotein may restrict in vivo ocular drug absorption, resulting in low ocular bioavailability.

Functional expression of a sodium dependent nucleoside transporter on rabbit cornea: Role in corneal permeation of acyclovir and idoxuridine.

Purpose: The major objectives were to investigate functional expression of nucleoside transporters on the rabbit cornea and to delineate mechanism of corneal permeation of acyclovir (ACV) and idoxuridine (IDU). Methods. Transport studies were conducted with isolated rabbit corneas at 34 degrees C using [(3)H]thymidine, [(3)H]ACV and [(3)H]IDU.