OKT3 prevents xenogeneic GVHD and allows reliable xenograft initiation from unfractionated human hematopoietic tissues.

Immunodeficient mice are now readily engrafted with human hematopoietic cells. However, these mice are susceptible to graft-versus-host disease (GVHD) induced by the engraftment and rapid expansion of coinjected human T cells. Therefore, highly purified sample populations must be used, adding significant time, expense, and effort. Here, we have explored in vivo and in vitro methods utilizing anti-T-cell antibodies to circumvent this problem. Intraperitoneal injection of the antibody within 48 hours prevented GVHD. Alternatively, short-term in vitro incubation of cells with antibody immediately before transplant was equally effective. Although in vitro antithymocyte globulin treatment resulted in a dramatic loss of SCID-repopulating cells (SRCs), treatment with OKT3 or UCHT1 abrogated GVHD risk and preserved engraftment potential. Leukemia samples that presented with substantial human T-cell contamination were effectively rescued from GVHD. In addition, OKT3 treatment of unfractionated cord blood resulted in robust engraftment of primary and secondary mice that was indistinguishable from grafts obtained using purified CD34(+) cells. Limiting dilution analysis of unfractionated blood demonstrated a SRC frequency of 1 in 300 to 500 CD34(+) cells, similar to that of purified hematopoietic stem and progenitor cells. This protocol streamlines xenograft studies while significantly reducing the cost and time of the procedure.

Formulation development and evaluation of mouth dissolving film of domperidone.

The present investigation was undertaken with the objective of formulating mouth dissolving film(s) of the antiemetic drug Domperidone to enhance the convenience and compliance by the elderly and pediatric patients. Domperidone is a drug of choice in case of nausea and vomiting produced by chemotherapy, migraine headaches, food poisoning and viral infections. It causes dopamine (D2 and D3) receptor blockage both at the chemoreceptor trigger zone and at the gastric level. It shows high first pass metabolism which results in poor bioavailability (10-15%). In view of high first pass metabolism and short plasma half-life it is an ideal candidate for rapid release drug delivery system. The solid dispersions of Domperidone were prepared with the use ß-cyclodextrin in various ratios (1:1, 1:2, 1:3) and solubility study was performed to determine the ratio in which solubility of Domperidone was highest (1:3). The selected solid dispersions were then utilized for the preparation of film by solvent casting method utilizing HPMC E15 as a film forming agent and PEG-400 as plasticizer. Five formulae were prepared and were evaluated for their in vitro dissolution characteristics, in vitro disintegration time, and their physico-mechanical properties. The promising film (F1) showed the greatest drug dissolution (more than 75% within 15 min), satisfactory in vitro disintegration time (45 sec) and physico-mechanical properties that are suitable for mouth dissolving films.

Formulation and evalution of montelukast sodium - chitosan based spray dried microspheres for pulmonary drug delivery.

The objective of present work was to prepare microspheres of montelukast sodium using a natural polymer- chitosan by spray drying method by using glutaraldehyde as a cross linking agent. The microspheres were characterized for size, shape, dissolution, swelling and mucoadhesion. It was observed that, all microspheres were spherical in shape with narrow size distribution. Microspheres had mean particle size of 7-12 µm, with % encapsulation efficiency of 78-86%. The % yield was 32-49% and drug load was 48-53%. With the increase in proportion of chitosan in formulation mucoadhesive strength was increase and also increased in particle size of microspheres. As the drug:polymer ratio increase drug loading was increase and % encapsulation efficiency was also increase.