Nanomedicine is a relatively new and rapidly evolving field combining nanotechnology with the biomedical and pharmaceutical sciences.1-3 Nanoparticles (NPs) can impart many pharmacokinetic, efficacy, safety, and targeting benefits when they are included in drug formulations.1-5 Many nanodrugs have entered clinical practice, and even more are being investigated in clinical trials for a wide variety of indications.2 However, nanopharmaceuticals also face challenges, such as the need for better characterization, possible toxicity issues, a lack of specific regulatory guidelines, cost-benefit considerations, and waning enthusiasm among some health care professionals. 4,5 For these reasons, expectations regarding nanodrugs that are in early stages of development or clinical trials need to remain realistic.4.

Progress in Nanomedicine: Approved and Investigational Nanodrugs.

Nanoparticles for oral delivery: Design, evaluation and state-of-the-art.

Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery - An update.

D-ɑ-tocopheryl polyethylene glycol succinate (Vitamin E TPGS or TPGS) has been approved by FDA as a safe adjuvant and widely used in drug delivery systems. The biological and physicochemical properties of TPGS provide multiple advantages for its applications in drug delivery like high biocompatibility, enhancement of drug solubility, improvement of drug permeation and selective antitumor activity. Notably, TPGS can inhibit the activity of ATP dependent P-glycoprotein and act as a potent excipient for overcoming multi-drug resistance (MDR) in tumor. In this review, we aim to discuss the recent advances of TPGS in drug delivery including TPGS based prodrugs, nitric oxide donor and polymers, and unmodified TPGS based formulations. These potential applications are focused on enhancing delivery efficiency as well as the therapeutic effect of agents, especially on overcoming MDR of tumors. It also demonstrates that the clinical translation of TPGS based nanomedicines is still faced with many challenges, which requires more detailed study on TPGS properties and based delivery system in the future.

Recent Advances in the Application of Vitamin E TPGS for Drug Delivery.

In vitro drug release kinetics studies are routinely performed to examine the ability of new drug formulations to modulate drug release. The underlying assumption is that the studies are performed in a sufficiently dilute solution, where the drug release is not limited by the solubility and the difference in release kinetics profile reflects the performance of a drug carrier in vivo. This condition is, however, difficult to meet with poorly water-soluble drug formulations, as it requires a very large volume of release medium relative to the formulation mass, which makes it challenging to measure the drug concentration accurately. These difficulties are aggravated with nanoparticle (NP) formulations, which are hard to separate from the release medium and thus require a dialysis bag or repeated high-speed centrifugation for sampling. Perhaps for these reasons, drug release kinetics studies of NPs of poorly water-soluble drugs are often performed in suboptimal conditions in which the NPs are not sufficiently diluted. However, such a practice can potentially underestimate drug release from NPs, leading to an inaccurate prediction that the NPs will attenuate the drug activity in vivo. Here we perform release kinetics studies of two different NP formulations of paclitaxel, a representative poorly water-soluble drug, according to common practices in the literature. We find that the drug release from NPs can be substantially underestimated depending on the choice of the release medium, NP/medium ratio, and handling of release samples. We discuss potential consequences of underestimating drug release, ending with suggestions for future studies with NP formulations of poorly water-soluble drugs.

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Release Kinetics Study of Poorly Water-Soluble Drugs from Nanoparticles: Are We Doing It Right?

The limited solubility and dissolution rate exhibited by poorly soluble drugs is major challenges in the pharmaceutical process. Following oral administration, the poorly soluble drugs generally show a low and erratic bioavailability which may lead to therapeutic failure. Pure drug nanocrystals, generated by “bottom up” or “top down” technologies, facilitate a significant improvement on dissolution behavior of poorly soluble drugs due to their enormous surface area, which in turn lead to substantial improvement in oral absorption. This is the most distinguished achievement of drug nanocrystals among their performances in various administration routes, reflected by the fact that most of the marketed products based on the nanocrystals technology are for oral application. After detailed investigations on various technologies associated with production of drug nanocrystals and their in vitro physicochemical properties, during the last decade more attentions have been paid into their in vivo behaviors. This review mainly describes the in vivo performances of oral drug nanocrystals exhibited in animals related to the pharmacokinetic, efficacy and safety characteristics. The technologies and evaluation associated with the solidification process of the drug nanocrystals suspensions were also discussed in detail.

Application of Drug Nanocrystal Technologies on Oral Drug Delivery of Poorly Soluble Drugs

Paclitaxel nanosuspension coated with P-gp inhibitory surfactants: II. Ability to reverse the drug-resistance of H460 human lung cancer cells.

Background Periodontitis is a localized inflammatory disorder. If not treated timely, the disease can result in loosening and subsequent loss of teeth. In situ hydrogel prepared with phase separation technique has emerged as an attractive alternative for periodontal pocket injection. Objective Minocycline (MCL)-loaded in situ hydrogel was prepared composed of poly(lactide-coglycolide) (PLGA) and N-methylpyrrolidone (NMP) to improve the topical treatment effect of periodontitis. Method A series of reasonable and applicable formulations were optimized by investigating their syringeability, viscosity and in vitro drug release. The rheological profiles, antimicrobial activities and pharmacodynamics were further studied to evaluate its effect on periodontitis treatment. Results The prepared MCL/PLGA hydrogel exhibited the characteristic of Newton fluid with acceptable syringeability. Drug release could last for more than 48 hours with an acceptable "burst release". It also had obvious antimicrobial activities and pharmacodynamics efficiency similar to the commercial product, Parocline®. Conclusion MCL/PLGA in situ hydrogel may be a promising clinical formulation for periodontitis treatment.

Fang Wang

Papers

Application of Drug Nanocrystal Technologies on Oral Drug Delivery of Poorly Soluble Drugs

Paclitaxel nanosuspension coated with P-gp inhibitory surfactants: II. Ability to reverse the drug-resistance of H460 human lung cancer cells.

Minocycline-loaded In situ Hydrogel for Periodontitis Treatment