Nanoparticle (NP) size has been shown to significantly affect the biodistribution of targeted and non-targeted NPs in an organ specific manner. Herein we have developed NPs from carboxy-terminated poly(d,L-lactide-co-glycolide)-block-poly(ethylene glycol) (PLGA-b-PEG-COOH) polymer and studied the effects of altering the following formulation parameters on the size of NPs: (1) polymer concentration, (2) drug loading, (3) water miscibility of solvent, and (4) the ratio of water to solvent. We found that NP mean volumetric size correlates linearly with polymer concentration for NPs between 70 and 250 nm in diameter (linear coefficient=0.99 for NPs formulated with solvents studied). NPs with desirable size, drug loading, and polydispersity were conjugated to the A10 RNA aptamer (Apt) that binds to the prostate specific membrane antigen (PSMA), and NP and NP-Apt biodistribution was evaluated in a LNCaP (PSMA+) xenograft mouse model of prostate cancer. The surface functionalization of NPs with the A10 PSMA Apt significantly enhanced delivery of NPs to tumors vs. equivalent NPs lacking the A10 PSMA Apt (a 3.77-fold increase at 24h; NP-Apt 0.83%+/-0.21% vs. NP 0.22%+/-0.07% of injected dose per gram of tissue; mean+/-SD, n=4, p=0.002). The ability to control NP size together with targeted delivery may result in favorable biodistribution and development of clinically relevant targeted therapies.

Topical treatment of superficial wounds has many advantages including decreased cost and increased ease of application compared with systemic treatments. Many of the advantages, however, are lost when it is necessary for repeated doses of topical medications to be given over an extended period of time. Therefore, a drug-delivery vehicle that delivers biologically appropriate doses in a sustained fashion would prove valuable. In this study, an alginate hydrogel scaffold impregnated with the angiogenic chemokine stromal-derived factor-1 was used to provide targeted, though short-term, delivery directly into the wound bed. Wounds were created on the dorsum of mice, and either a stromal-derived factor-1-impregnated or a saline-impregnated scaffold was applied. Wounds were explanted after 1, 3, 7 days, wound area was measured, and histology and immunohistochemistry for endothelial markers were performed. The remaining wound area in stromal-derived factor-1-treated wounds vs. controls was not significant 1 day after wounding (96.7 ± 0.1 vs. 97.5 ± 1.1%, p=0.317), but was significant after 3 days postwounding (46.7 ± 0.1 vs. 82.3 ± 2.4%, p=0.046) and 7 days postwounding (2.3 ± 1.3 vs. 32.0 ± 4.0%, p=0.049). Immunohistochemistry revealed a greater degree of endothelial cell invasion into the wound bed infiltration compared with controls. The results of this study suggest significant clinical promise for our hydrogel-delivery vehicle in the treatment of wounds.

PurposeUse of polypropylene mesh (PPM) in hernia repair is associated with tissue reactivity. We examined, in a rat model, a novel non-biodegradable hydrogel coated PPM which may allow for decreased inflammation and a decreased foreign body reaction.MethodsThrough a dorsal midline incision, a 2 cm × 2 cm section of PPM (either coated or uncoated) was placed on the fascial surface 1.5 cm from the incision on the dorsal wall of Sprague–Dawley rats. At 2 and 12 weeks after placement, the PPM and surrounding tissue were harvested. A board-certified dermatopathologist examined H&E stained slides for fibrosis and foreign body reaction. In addition, tissues were stained for apoptotic cells, oxidative damage, macrophages, fibroblasts, neovascularization and metalloproteases.ResultsAt 2 and 12 weeks, there was a greater than 95 % decrease in foreign body giant cells in coated PPM samples compared to uncoated; fibrosis was decreased by 50 %. At 2 and 12 weeks, oxidative damage, fibroblast accumulation, apoptosis and macrophages were significantly decreased in coated PPM samples compared to uncoated PPM.ConclusionThese results demonstrate that a non-biodegradable hydrogel coating of PPM led to significant reduction in foreign body reaction, oxidative stress and apoptosis compared to uncoated PPM in vivo, and suggest that this coating could be clinically useful in hernia repair.

Hydrogen sulfide significantly attenuates ischemia-reperfusion injury in intestinal tissue in vitro and in vivo. These results have significant implications for enteric free tissue transfers and other gastrointestinal procedures in which ischemic intervals may be anticipated.

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