Mitigation of Hydrochloric Acid (HCl)-Induced Lung Injury in Mice by Aerosol Therapy of Surface-Active Nanovesicles Containing Antioxidant and Anti-inflammatory Drugs.

Acute lung injury leading to alveolar inflammation and surfactant dysfunction remains a medical challenge. Surface-active lipid nanovesicles of 200-250 nm size with antioxidant D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) and anti-inflammatory drug dexamethasone disodium phosphate (DXP) dual combination (Dual-NV) were developed for delivery as aerosols by nebulization in acid lung injury models. Drug deposition studies showed Dual-NV deposited ∼2.

Exploitation of sub-micron cavitation nuclei to enhance ultrasound-mediated transdermal transport and penetration of vaccines.

Inertial cavitation mediated by ultrasound has been previously shown to enable skin permeabilisation for transdermal drug and vaccine delivery, by sequentially applying the ultrasound then the therapeutic in liquid form on the skin surface. Using a novel hydrogel dosage form, we demonstrate that the use of sub-micron gas-stabilising polymeric nanoparticles (nanocups) to sustain and promote cavitation activity during simultaneous application of both drug and vaccine results in a significant enhancement of both the dose and penetration of a model vaccine, Ovalbumin (OVA), to depths of 500μm into porcine skin. The nanocups themselves exceeded the penetration depth of the vaccine (up to 700μm) due to their small size and capacity to 'self-propel'.

Ultrasound-Propelled Nanocups for Drug Delivery.

Ultrasound-induced bubble activity (cavitation) has been recently shown to actively transport and improve the distribution of therapeutic agents in tumors. However, existing cavitation-promoting agents are micron-sized and cannot sustain cavitation activity over prolonged time periods because they are rapidly destroyed upon ultrasound exposure. A novel ultrasound-responsive single-cavity polymeric nanoparticle (nanocup) capable of trapping and stabilizing gas against dissolution in the bloodstream is reported.

Inertial cavitation to non-invasively trigger and monitor intratumoral release of drug from intravenously delivered liposomes.

The encapsulation of cytotoxic drugs within liposomes enhances pharmacokinetics and allows passive accumulation within tumors. However, liposomes designed to achieve good stability during the delivery phase often have compromised activity at the target site. This problem of inefficient and unpredictable drug release is compounded by the present lack of low-cost, non-invasive methods to measure such release.

Effect of D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on surfactant monolayers.

In the present study, the effects of an amphiphilic polymer, d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS) on model surfactant monolayers dipalmitoylphosphatidylcholine (DPPC), a binary mixture of DPPC with palmitoyloleoyl phosphatidylglycerol (DPPC-POPG) 9:1 (w/w) and binary mixture of DPPC and oleic acid (DPPC-OA) were evaluated. The ability of TPGS to act as an antioxidant adjuvant for pulmonary surfactants was also evaluated. Compression isotherms of surfactant monolayers at 37 °C in a Langmuir-Blodgett trough showed that DPPC and DPPC:TPGS mixed monolayers (1:0.