Biologically adhesive delivery systems offer important advantages over conventional drug delivery systems. Here we show that engineered polymer microspheres made of biologically erodable polymers, which display strong adhesive interactions with gastrointestinal mucus and cellular linings, can traverse both the mucosal absorptive epithelium and the follicle-associated epithelium covering the lymphoid tissue of Peyer's patches. The polymers maintain contact with intestinal epithelium for extended periods of time and actually penetrate it, through and between cells. Thus, once loaded with compounds of pharmacological interest, the microspheres could be developed as delivery systems to transfer biologically active molecules to the circulation. We show that these microspheres increase the absorption of three model substances of widely different molecular size: dicumarol, insulin and plasmid DNA.
Successful autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation depend on safe hematopoietic stem cell (HSC) cryopreservation and storage. Several successful methods for cryopreservation and storage have been established and are commonly used all over the world. However, little is known about the effects of long-term cryopreservation on the capacity to sustain a complete immunohematopoietic engraftment. Several authors have investigated stem cell viability after cryopreservation and storage for more than 5 years and reported preclinical good viabilities in terms of dye-exclusion or colony-forming capability in vitro. Only two studies using BM cryopreserved for more than 5 years for transplantation are reported, but they did not provide proof of trilineage engraftment. In February 1997 at our institution, a patient with relapsed non-Hodgkin's lymphoma underwent ABMT with BM harvested in February 1990. He achieved a granulocyte count > 500 x 10(6)/L on day 21 and a self-supporting platelet count > 20 x 10(9)/L on day 30. After day 29, his hemoglobin level was satisfactory without need of transfusion support. This successful trilineage engraftment with cryopreserved BM that had been stored for 7 years suggests that HSC are able to maintain their capability to reconstitute hematopoiesis for a long time.
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