Combined Effects of Drugs and Plasticizers on the Properties of Drug Delivery Films.

Formation of scar tissue may be reduced or prevented if wounds were locally treated with a combination of molecules tuned to the different healing phases, guiding tissue regeneration along a scar free path. To this end, drug delivery devices made of cellulose acetate phthalate and Pluronic F-127 were loaded with either quercetin or pirfenidone and plasticized with either triethyl citrate (TEC) or tributyl citrate (TBC). Quercetin inhibits oxidative stress, and pirfenidone has been shown to reduce production of pro-inflammatory and fibrogenic molecules. The combined effects of drug and plasticizer on erosion, release, and mechanical properties of the drug delivery films were investigated. TEC-plasticized films containing quercetin released drug at a slower rate than did TBC films. Pirfenidone-loaded films released drug at a faster rate than erosion occurred for both types of plasticizers. Higher plasticizer contents of both TEC and TBC increased the elongation and decreased the elastic modulus. In contrast, increased pirfenidone loading in both TEC and TBC films resulted in a significantly higher modulus, an anti-plasticizer effect. Adding pirfenidone significantly decreased elongation for all film types, but quercetin-loaded samples had significantly greater elongation with increasing drug content. Films containing quercetin elongated more than did pirfenidone-loaded films. Quercetin is over 1.5 times larger than pirfenidone, has water solubility over 12 times lower, and has 6 times more bonding sites than pirfenidone. These differences affected how the two drugs interacted with cellulose acetate phthalate and Pluronic F-127 and thereby determined polymer properties. Drug release, erosion, and mechanical properties of association polymer films can be tailored by the characteristics of the drugs and plasticizers included in the system.

Sequential Release of Multiple Drugs from Flexible Drug Delivery Films.

Sequential release of drugs aligned with the phases of tissue healing could reduce scarring. To achieve this aim, layered film devices comprising cellulose acetate phthalate (CAP) and Pluronic F-127 (Pluronic) were loaded with ketoprofen, quercetin, and pirfenidone. Citrate plasticizers were added to impart flexibility. Release of two or three drugs in sequence over several days was obtained for all multilayered devices tested. Mechanical analysis showed that elongation increased and modulus decreased with increasing plasticizer content. Release profiles can be tailored by order of layers, plasticizer concentration, and drug loaded, making CAP-Pluronic an appealing system for inhibiting scar tissue formation.

Blinded, multicenter comparison of methods to detect a drug-resistant mutant of human immunodeficiency virus type 1 at low frequency.

We determined the abilities of 10 technologies to detect and quantify a common drug-resistant mutant of human immunodeficiency virus type 1 (lysine to asparagine at codon 103 of the reverse transcriptase) using a blinded test panel containing mutant-wild-type mixtures ranging from 0.01% to 100% mutant. Two technologies, allele-specific reverse transcriptase PCR and a Ty1HRT yeast system, could quantify the mutant down to 0.1 to 0.4%. These technologies should help define the impact of low-frequency drug-resistant mutants on response to antiretroviral therapy.