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The aim of this work was to design a biodegradable delivery system for oligonucleotides providing both a sustained release and an improved intracellular penetration. To this purpose oligonucleotide/polyethylenimine (ON/PEI) complexes at nitrogen to phosphate (N/P) molar ratios of about 15 or 40 were encapsulated into poly(lactide-co-glycolide) microspheres by the multiple emulsion−solvent evaporation technique. ON/PEI complexes were efficiently entrapped inside microspheres. The introduction of salts within the external aqueous phase allowed an improvement of microsphere characteristics. In particular, the use of sodium chloride led to a reduced microsphere porosity and a more homogeneous ON distribution inside the polymeric matrix. These effects were attributed to the reduced flux of water from the external aqueous phase toward the internal aqueous droplets, due to the osmotic effect of sodium chloride. Both, the reduced porosity and the improved ON distribution inside the matrix, were considered responsible for the lower burst effect and the slower ON release rate from microsphere prepared with sodium chloride. ON/PEI complexes encapsulated inside microspheres were also protected toward enzymatic degradation in fetal calf serum. Interestingly, ON/PEI complexes slowly released from microspheres efficiently penetrated inside HeLa cells and oligonucleotides were preferentially located in the nucleus.

This study describes the synthesis of novel biodegradable graft copolymers based on a backbone of poly Llactic acid PLLA on which short blocks of polyacrylamide PAcr were grafted. Preliminary results of their potential in the field of controlledrelease technologies also have been reported. The copolymers have been synthesized through the radical polymerization of acrylamide initiated by a peroxide in the presence of PLLA. Two different methodologies of synthesis, namely, in solution and in emulsion, have been tested. The structure of the copolymers was studied by 1HNMR and infrared spectroscopy and by differential scanning calorimetry DSC and cytotoxicity tests were conducted to assess their biocompatibility. The copolymers were used to prepare particles by the emulsion–solvent evaporation technique. The shapes and dimensions of the particles were dependent on the polymer type and concentration used. The surfaces of the particles were modified by the presence of polyacrylamide residues, as demonstrated by ζpotential measurements. The release behavior of the particles was assessed by encapsulating rhodamine B as the model compound. The release was faster for the particles prepared by the grafted polymer as a consequence of its increased hydrophilicity. Based on these novel biomaterials, preliminary results suggest a potential of the particles for peroral or parenteral drug delivery. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 62: 244–253, 2002

AbstractThe effect of ricinoleic acid on nitric oxide synthase (NOS) activity has been investigated in the rat. NOS, determined by the oxidation of oxyhemoglobin to methemoglobin or by the formation of citrulline, was detected in homogenates of both ileal and colonic tissue. Ricinoleic acid (10−5–10−3M) incubated with intestinal tissue for 15 min, increased NOS activity(P <0.05–0.01); however the effect was more evident in the ileum than in the colon. A pretreatment with NG-nitro-L-arginine methyl ester (L-NAME, 6.25–25 mg kg−1i.p., 15 min before the removal of tissue) inhibited the increase in NOS activity(P < 0.05). These findings confirm an involvement of NO in the laxative effect of ricinoleic acid (castor oil).

About 1 of every 50 women of child‐bearing age who have a functioning kidney transplant become pregnant. Successful pregnancies following kidney allotransplantation with conventional immunosuppressive treatment are well described [8], and there is no evidence of abnormalities in the infants born. The use of cyclosporine (CSA) means new problems for the pregnant women and the fetus: the risk of congenital abnormalities, fetal growth retardation, hepato‐ and nephrotoxicity. We report the experience of 16 pregnancies in 16 of our kidney transplant patients, of which 7 were treated with CSA.