Efficiency of Dispatch and Infiltrator cardiac infusion catheters in arterial localization of nanoparticles in a porcine coronary model of restenosis.

Localized intramural delivery of sustained release biodegradable nanoparticles containing an antiproliferative agent could provide prolonged drug effect at the site of vascular injury that could inhibit the proliferation of smooth muscle cells and hence restenosis. The efficiency of arterial localization of nanoparticles is crucial in maximizing the drug effect in the target tissue. Therefore, the objective of the present study was to determine the comparative efficiency of the Dispatch and the Infiltrator cardiac infusion catheters to localize nanoparticles in the arterial wall. Following a standard balloon angioplasty procedure on the left anterior descending artery (LAD) in a porcine coronary model of restenosis, a suspension of nanoparticles containing a fluorescent marker was infused at the site of injury using either the Dispatch or the Infiltrator catheter. One hour following the infusion, animals were sacrificed and the nanoparticle levels in the LAD and other tissue were analyzed. The Dispatch catheter resulted in 3.3 folds greater efficiency of nanoparticle localization in the LAD than the Infiltrator catheter (309 +/- 124 vs. 93 +/- 43 microg/g of tissue, n = 6 for Dispatch and n = 5 for Infiltrator, p = 0.082, t-test). It is estimated that about 2% of the arterial volume can be displaced with the nanoparticle infusion. Fluorescence microscopy of the cross-sections of the LAD revealed greater fluorescence activity in the intimal layer with both the catheters, however the arteries infused using the Dispatch catheter demonstrated relatively higher degree of fluorescence activity in the medial and adventitial layers. The transmission electron microscopy of the arterial sections demonstrated infiltration of nanoparticles in the arterial wall and the histological analysis of the sections demonstrated no apparent damage to the endothelium due to the infusion of nanoparticles.

Evaluation of new rosin derivatives for pharmaceutical coating.

Rosin and Rosin-based polymers have diversified drug delivery applications achieving sustained/controlled release profiles. In this manuscript, two new Rosin derivatives were synthesized and evaluated for physicochemical properties, molecular weight, polydispersity and glass transition temperature. Plasticizer-free films prepared by solvent evaporation were tested for surface morphology, water vapour transmission and mechanical properties (tensile strength, percent elongation and modulus of elasticity). The films showed low tensile strength and high percent elongation values achieving smooth and uniform surface. The derivatives were further characterized for film coating by evaluating the release of a model drug (diclofenac sodium) from pellets coated with the rosin derivatives as retarding membrane. Drug release was sustained up to 10 h due to 10% (w/w) coat built up with the new rosin derivatives. Increase in coat-built-up further facilitated sustained release from coated forms. Film coating could be achieved without agglomeration of the pellets within a reasonable operating time. The present study proposes novel film forming materials with potential use in sustained drug delivery.

Honokiol: a novel natural agent for cancer prevention and therapy.

Honokiol (3',5-di-(2-propenyl)-1,1'-biphenyl-2,4'-diol) is a bioactive natural product derived from Magnolia spp. Recent studies have demonstrated anti-inflammatory, anti-angiogenic, anti-oxidative and anticancer properties of honokiol in vitro and in preclinical models. Honokiol targets multiple signaling pathways including nuclear factor kappa B (NF-κB), signal transducers and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR) and mammalian target of rapamycin (m-TOR), which have great relevance during cancer initiation and progression. Furthermore, pharmacokinetic profile of honokiol has revealed a desirable spectrum of bioavailability after intravenous administration in animal models, thus making it a suitable agent for clinical trials. In this review, we discuss recent data describing the molecular targets of honokiol and its anti-cancer activities against various malignancies in pre-clinical models. Evaluation of honokiol in clinical trials will be the next step towards its possible human applications.