Stable and sustained release liposomal formulations of celecoxib: In vitro and in vivo anti-tumor evaluation.

Celecoxib (CLX) is a selective COX-2 inhibitor with anticancer potential in a COX-2 dependent and independent manner. CLX's low water solubility has a dose limiting effect on its utilization in cancer treatment. Here, we developed liposomal drug delivery systems to allow a systemic administration and increase tumor accumulation of CLX based on the enhanced permeability and retention (EPR) mechanism. Nine liposomal formulations has been prepared with different phospholipid compositions; among them three sets of liposomal formulations were selected based on characterization and stability for further studies. Anti-tumor effects of CLX-entrapped liposomal formulations were tested in vitro by cytotoxicity test and in vivo in BALB/c mice bearing C26 colon carcinoma. Biodistribution of liposomal-CLX has been studied by radiolabeling of CLX with I125.The selected formulations had average size of about 100 nm, a narrow monomodal distribution with storage stability of at least one year at 4 °C. The HSPC/DSPG/cholesterol/DSPE-PEG2000/CLX (65/10/10/5/10 M ratio) liposomal formulation had slowest release profile and greatest antitumor effects in vivo. This liposomal I125CLX formulation had a three times more accumulation in tumor site in comparison to the free I125CLX. Liposomal CLX may serve as a safe, slow release and effective anti-tumor agent and merits further investigation.

New approach for the treatment of neuropathic pain: Fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells.

BACKGROUND: Neuropathic pain triggered by peripheral nerve lesion is extremely difficult to manage with current approaches, hence the importance of exploring therapeutic alternatives. METHODS: We have analysed adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs FGF1 ) on chronic constriction injury (CCI). The mechanical and thermal hypersensitivity were assessed using the von Frey filament, radiant heat and acetone drop tests. Histopathological and apoptotic changes and the level of FGF1, GFAP and TNFα proteins were assessed in the lumbar portion (L4-L6). Moreover, AD-MSCs FGF1 were labelled with 99m Tc -HMPAO and isolated organ counting were performed upon AD-MSCs FGF1 administration. RESULTS: Administration of AD-MSCs FGF1 attenuated the CCI-induced mechanical and thermal hypersensitivity. Spinal structural alterations and apoptosis were decreased in the AD-MSCs FGF1 group. The injection of either phosphate-buffered saline or normal NIH3T3 fibroblasts could not attenuate the behavioural symptoms of neuropathic pain. Increased genetically engineered cells were counted in the injured sciatic nerve and the elevated levels of FGF1 were detected in the spinal tissue. Stem cell therapy lead to decrement the level of the CCI-induced TNF-α and GFAP expression. CONCLUSION: The intravenous administration of AD-MSCs FGF1 could be considered as a potential remedy for the management of neuropathic pain. SIGNIFICANCE: AD-MSCs FGF1 attenuated the CCI-induced mechanical and thermal hypersensitivity. Spinal structural alterations and apoptosis were significantly decreased in the AD-MSCs FGF1 group. Elevated levels of FGF1 were detected in the spinal tissue.

Erosions and ulcers of the vulva: diagnosis, incidence, and management.

In a study of 877 patients with disorders of the vulva seen at a vulva clinic, 375 (43%) presented with an erosion or ulceration or a condition in which an erosion or ulceration developed as a complicating feature. One hundred sixty-one of these patients had a sexually transmitted disease. This report identifies the conditions associated with erosions and ulcerations of the vulva by incidence and provides a simple clinical classification of them as an aid in diagnosis. Methods of study of this group of diseases and their management are discussed.