Structural insights into loss of function of a pore forming toxin and its role in pneumococcal adaptation to an intracellular lifestyle.

The opportunistic pathogen Streptococcus pneumoniae has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and the other of a deadly pathogen invading sterile host compartments. The latter triggers an overwhelming inflammatory response, partly driven via pore forming activity of the cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, the primary reservoir for pneumococcus, it also contributes to high mortality rates, creating a bottleneck that hampers widespread bacterial dissemination, thus acting as a double-edged sword.

Stratum corneum modulation by chemical enhancers and lipid nanostructures: implications for transdermal drug delivery.

Skin is the outermost and largest protective covering of the body. The uppermost layer of the skin, stratum corneum also called the horny layer is composed of keratin-filled cells covered by a lipid matrix which shields the skin from physical and chemical entrants. The lipid lamellar structure comprises of ceramides, cholesterol, fatty acids and proteins.

Synergistic locoregional chemoradiotherapy using a composite liposome-in-gel system as an injectable drug depot.

The use of radiosensitizers in clinical radiotherapy is limited by systemic toxicity. The biopolymeric, biodegradable, injectable liposome-in-gel-paclitaxel (LG-PTX) system was developed for regional delivery of the radiosensitizer paclitaxel (PTX), and its efficacy was evaluated with concurrent fractionated radiation. LG-PTX is composed of nano-sized drug-loaded fluidizing liposomes, which are incorporated into a porous biodegradable gellan hydrogel.

Urothelium-adherent, ion-triggered liposome-in-gel system as a platform for intravesical drug delivery.

Instillations of therapeutic agents into the urinary bladder have limited efficacy due to drug washout and inadequate attachment to and penetration into the bladder wall. Instilled nanoparticles alone have low stability and high susceptibility to washout, while gel-based systems are difficult to administer and retain. To overcome disadvantages of current technologies, a biodegradable, in situ-gelling liposome-in-gel (LP-Gel) system was developed for instillation into the bladder, composed of nano-sized, fluidizing liposomes incorporated into a "smart" biopolymeric, urine-triggered hydrogel.

Intravesical drug delivery: Challenges, current status, opportunities and novel strategies.

The urinary bladder has certain unique anatomical features which enable it to form an effective barrier to toxic substances diffusing from the urine into the blood. The barrier function is due to the epithelial surface of the urinary bladder, the urothelium, which has characteristic umbrella cells, joined by tight junctions and covered by impenetrable plaques, as well as an anti-adherent mucin layer. Diseases of the urinary bladder, such as bladder carcinomas and interstitial cystitis, cause acute damage to the bladder wall and cannot be effectively treated by systemic administration of drugs.