Pharmacokinetics of once-daily boosted elvitegravir when administered in combination with acid-reducing agents.

Background: Acid-reducing agents are commonly used co-medications by HIV-1-infected patients receiving antiretroviral treatment. The effects of various representative acid-reducing agents on the pharmacokinetics (PK) of boosted elvitegravir were evaluated by 1-way interaction in 4 studies.

Methods: Healthy subjects received ritonavir-boosted elvitegravir (EVG/r; 50/100 mg QD) administered alone or with antacid simultaneously in Study 1, staggered (±2 or ±4 hours) or with omeprazole in Study 2; Studies 3 and 4 evaluated cobicistat-boosted elvitegravir (EVG/co; 150/150 mg QD) administered simultaneously or staggered (+12 hours) with famotidine or omeprazole.

In-vivo efficacy of novel paclitaxel nanoparticles in paclitaxel-resistant human colorectal tumors.

Colloidal carriers have been shown to improve tumor therapy by increased drug delivery into tumor sites resulting directly from the enhanced permeability and retention effect (EPR). However, the clinical outcome of tumor therapy is often limited due to multidrug resistance. Several different types of resistance exist with expression of p-glycoprotein being the most commonly described.

Nanoparticle surface charges alter blood-brain barrier integrity and permeability.

Purpose: The blood-brain barrier (BBB) presents both a physical and electrostatic barrier to limit brain permeation of therapeutics. Previous work has demonstrated that nanoparticles (NPs) overcome the physical barrier, but there is little known regarding the effect of NP surface charge on BBB function. Therefore, this work evaluated: (1) effect of neutral, anionic and cationic charged NPs on BBB integrity and (2) NP brain permeability.

Paclitaxel nanoparticles for the potential treatment of brain tumors.

Despite the advances in tumor therapy, patients with primary brain tumors and brain metastases have a very poor prognosis. Low responses to chemotherapy are mainly attributed to impermeability of the blood-brain barrier to cytotoxic agents. Paclitaxel has been shown to be active against gliomas and various brain metastases.

In situ blood-brain barrier transport of nanoparticles.

Purpose: Two novel types of nanoparticles were evaluated as poten tial carriers for drugs across the blood-brain barrier (BBB).

Methods: Nanoparticles were composed of biocompatible materials including emulsifying wax (E. Wax) or Brij 72.

Brain uptake of thiamine-coated nanoparticles.

Recently, a novel nanoparticle (NP) comprised of emulsifying wax and Brij 78 was shown to have significant brain uptake using the in-situ rat brain perfusion technique. To further these studies and to specifically target brain, we have incorporated thiamine as a surface ligand on the nanoparticles. Solid nanoparticles were prepared from oil-in-water microemulsion precursors.

In vivo and in vitro assessment of baseline blood-brain barrier parameters in the presence of novel nanoparticles.

Purpose: Nanoparticles have advantage as CNS drug delivery vehicles given they disguise drug permeation limiting characteristics. Conflicting toxicological data, however, is published with regard to blood-brain barrier integrity and gross mortality.

Methods: To address this issue two novel nanoparticle types: "emulsifying wax/Brij 78" and "Brij 72/Tween 80 nanoparticles were evaluated in vivo for effect on cerebral perfusion flow, barrier integrity, and permeability using the in situ brain perfusion technique.