Evaluation of TRI-726 as a drug delivery matrix.

Background: The TRI-726 polymeric drug delivery matrix is a newly-developed biocompatible hydrogel exhibiting in situ reverse-thermal gelling, mucoadhesivity, and sustained-erosion properties.

Methods: Using two model drugs, clindamycin hydrochloride and acetaminophen, we determined the gelling temperatures, in vitro release profiles, kinetics of matrix erosion, rheological properties, mucoadhesive strength, microbiological activity of released clindamycin, and biocompatibility when in contact with cells.

Results: It was demonstrated that none of the excipients contained in the TRI-726 polymer matrix caused any loss in clindamycin?s antimicrobial activity following incorporation into the polymer matrix.

Canine periodontal disease control using a clindamycin hydrochloride gel.

Stabilizing or reducing periodontal pocket depth can have a positive influence on the retention of teeth in dogs. A topical 2% clindamycin hydrochloride gel (CHgel) was evaluated for the treatment of periodontal disease in dogs. The CHgel formulation provides for the sustained erosion of the matrix, but also flows into the periodontal pocket as a viscous liquid, and then rapidly forms a gel that has mucoadhesive properties and also may function as a physical barrier to the introduction of bacteria.

Inducing a change in the pharmacokinetics and biodistribution of poly-L-lysine in rats by complexation with heparin.

The aim of our study was to induce changes in the plasma elimination half-life (t(1/2)(elim)), rate and extent of urinary excretion, and biodistribution of a model macromolecule, poly-L-lysine, in rats following complexation with heparin. Male Sprague-Dawley rats were dosed intravenously with either unfractionated [(3)H]heparin, FITC-labelled poly-L-lysine, or an [(3)H]heparin:FITC-labelled poly-L-lysine complex. Serum and blood concentration vs time and urinary excretion profiles were determined as well as the resulting patterns of biodistribution to liver, spleen, kidney, and muscle tissue.

An attempt to modulate the microporous diffusion of a model polypeptide by altering its secondary structure.

The purpose of the present study was to determine whether intentional alteration of the secondary structure of a model polypeptide, conantokin-G, influenced the rate and extent of aqueous pore diffusion across a synthetic microporous membrane. Use of a microporous synthetic membrane allowed for analysis of polypeptide transport without the confounding variables of protein binding, acid- and/or enzyme-mediated degradation, endocytotic uptake, and enzymatic inactivation associated with a biological membrane. Conantokin-G was intentionally changed from its native random coil structure to the alpha-helix structure using calcium, and both structures were verified using circular dichroism.

Poly(L-lysine) as a model drug macromolecule with which to investigate secondary structure and microporous membrane transport, part 2: diffusion studies.

Peptide drugs are hydrophilic in nature and so their preferred pathway of membrane transport is by the paracellular route, which primarily involves passive diffusion across intercellular pores. The objective of the present study was to investigate the effect of secondary structure on the aqueous diffusion of a model polypeptide, poly(L-lysine), through a microporous membrane. The primary aim was to systematically evaluate the variables (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.