Current prodrug strategies via membrane transporters/receptors.

Prodrug design strategies have been employed to improve the delivery of drugs with undesirable pharmacokinetic properties such as chemical stability and lack of specificity. Targeted prodrug design represents a new strategy for site-directed and efficient drug delivery. Targeting of drugs to transporters and receptors to aid in site-specific carrier-mediated absorption is emerging as a novel and clinically significant approach.

Ocular disposition of ganciclovir and its monoester prodrugs following intravitreal administration using microdialysis.

The present study was carried out to delineate the ocular pharmacokinetics of ganciclovir (GCV) following intravitreal administration. Another objective was to achieve sustained therapeutic concentrations of GCV in the vitreous over a prolonged period of time using its acyl monoester prodrugs (acetate, propionate, butyrate, and valerate). New Zealand albino male rabbits (2-2.

Insulin aggregation and asymmetric transport across human bronchial epithelial cell monolayers (Calu-3).

The purpose of this work was to elucidate the transport pathways of zinc insulin across the Calu-3 cell monolayer, an in vitro model of the human airway epithelium. Calu-3 cells grown in liquid-covered conditions formed a confluent monolayer with a high transepithelial electrical resistance value of 1000 +/- 150 Omega small middle dot cm(2). The cell monolayer was characterized by a low mannitol permeability of 4.

Effect of mono- and di-acylation on the ocular disposition of ganciclovir: physicochemical properties, ocular bioreversion, and antiviral activity of short chain ester prodrugs.

A series of short-chain carboxylic mono- and diesters of ganciclovir were synthesized in our laboratory. Physico-chemical properties, i.e.

Poly(L-lysine) as a model drug macromolecule with which to investigate secondary structure and membrane transport, part I: Physicochemical and stability studies.

Low oral bioavailability of therapeutic peptides and proteins generally results from their poor permeability through biological membranes and enzymatic degradation in the gastrointestinal tract. Since different secondary structures exhibit different physicochemical properties such as hydrophobicity, size and shape, changing the secondary structure of a therapeutic polypeptide may be another approach to increasing its membrane permeation. Poly(L-lysine) was used as a model polypeptide.