Antitumor activity of the bioreductive prodrug 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) on MDA-MB-231 cells: in vitro and in vivo.

BACKGROUND: 3-(2-Nitrophenyl) propionic acid-paclitaxel (NPPA-PTX) is a paclitaxel (PTX) bioreductive prodrug synthesized by our lab. We hypothesize that NPPA-PTX can self-assemble to form nanoparticles (NPs). MATERIALS AND METHODS: In the present research, the theoretical partition coefficient (XlogP) and Hansen solubility parameters of NPPA-PTX were calculated. NPPA-PTX nanoparticles prepared by NPPA-PTX and DSPE-PEG (NPPA-PTX:DSPE-PEG =1:0.1, w/w) (NPPA-PTX@PEG NPs) were prepared and characterized. The cellular uptake, in vitro antitumor activity, in vivo targeting effect, tumor distribution, in vivo antitumor activity, and safety of NPPA-PTX@PEG NPs were investigated. RESULTS: Our results indicate that NPPA-PTX can self-assemble to form NPPA-PTX@PEG NPs. Both the cellular uptake and safety of NPPA-PTX@PEG NPs were higher than those of Taxol. NPPA-PTX@PEG NPs could target tumor tissues by a passive targeting effect. In tumor tissues, NPPA-PTX@PEG NPs could completely transform into active PTX. The in vivo antitumor activity of NPPA-PTX@PEG NPs was confirmed in MDA-MB-231 tumor-bearing nude mice. CONCLUSION: The bioreductive prodrug NPPA-PTX could self-assemble to form NPs. The safety and antitumor activity of NPPA-PTX@PEG were confirmed in our in vitro and in vivo experiments. The NPPA-PTX@PEG NPs developed in this study could offer a new way of preparing bioreductive prodrug, self-assembled NPs suitable for antitumor therapy.

[Tendencies of prescriptions for neuralgic pain in National Suruga Sanatorium (leprosy), Japan during last 11 years].

The number of ex-leprosy patients has reduced rapidly who were forced to be admitted under leprosy prevention/segregation law and are staying at national sanatoriums with different disabilities due to different physical and social reasons for long time in Japan. Most of them have been of clinically cured status for decades after effective chemotherapy. Some have still been suffering from acute or chronic neuralgic pains which are supposed to be long standing consequences of nerve damage of leprosy and getting medications for long period. Pharmacy department of National Suruga Sanatorium has studied the amount of prescriptions of some medicines for last 11 years, which were thought to be prescribed for pain including neuralgic pain. There seem to be some tendencies of medications during last decade. VitaminB12 (Mecobalamine) is one of the commonest drugs for neuralgic pain at this sanatorium and the amount of prescription had almost been unchanged through the years. Prescription of non-steroid anti-inflammatory drugs (NSAIDs) increased year by year, which may reflect the increasing age of ex-patients who need more pain killers for their painful joints or back. Loxoprofen is the most popular pain killer here and increased by ten times for last decade. The number of prescription for Pentazocine and Hydroxyzine Hydrochloride injection increased for last several years, which reflects a few patients who were still suffering from severe chronic neuralgia for years. It is desirable that a standard regimen for chronic neuralgic pain as a consequence of nerve impairment in leprosy will be developed as soon as possible.