PubMed · 11570679
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J F Roulet. 2001. A world without adhesion?. https://pubmed.ncbi.nlm.nih.gov/11570679/
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The aim was to evaluate the potential of specific bioadhesive nanoparticles to increase the oral bioavailability of pre-systemic degraded drugs, using 5-fluorouridine (FURD) as model. For this purpose, poly(methylvinylether-co-maleic anhydride) nanoparticles (NP), NP coated with albumin (BSA-NP) and NP treated with albumin and 1,3-diaminopropane (BD-NP) were used. All the formulations displayed a similar size and drug loading. However, BSA-NP showed a tropism for the stomach, NP developed adhesive interactions with both the stomach and middle portions of the small intestine and BD-NP with the distal regions of the small intestine. These formulations were orally administered to laboratory animals and the FURD levels in plasma, tissues and urine were quantified at different times. From the urine data, the FURD bioavailability when loaded in either BSA-NP or NP was about 79% and 21%, respectively. For the control oral solution and BD-NP this parameter was 11% and 2%, respectively. FURD metabolism in gut was assessed by HPLC analysis of the lumen content. A FURD metabolite was found. Comparing the three nanoparticle formulations, the presence of the metabolite in the lumen contents was significantly higher for BD-NP than for NP and BSA-NP. In summary, the use of bioadhesive nanoparticles with tropism for the stomach mucosa may be considered as an adequate alternative to increase the bioavailability of some pre-systemic metabolised drugs.
Sterilization capability is a necessary requirement for any material that is to be used in a medical application. Therefore, it is necessary for apatite cement (AC) to be sterilized. Because there is little information on the sterilization methods of AC, the aims of this investigation were to evaluate the effects of various sterilization methods, including steam, dry heat, ethylene oxide (EtO) gas, and gamma irradiation sterilizations, on the setting and mechanical properties of AC. In the case of steam sterilization, because AC powder aggregated before setting-time measurements, the setting time could not be measured. When the powder was sterilized by dry heat or EtO gas, the setting time was prolonged significantly and the wet diametral tensile strength (DTS) value decreased significantly. Therefore, sterilizations with steam, dry heat, or EtO gas were suggested to be inappropriate methods for AC. Accordingly, the following experiments focused on gamma sterilization. The setting time of AC was retarded with an increase in gamma irradiation dose. The wet DTS value decreased with the increase in gamma irradiation dose. There was no compositional change due to the gamma irradiation. The following tests were carried out in order to examine the effect of the gamma irradiation on the setting reaction of AC in detail. Tetracalcium phosphate [TTCP: Ca(4)(PO(4))(2)O] and dicalcium phosphate anhydrous (DCPA: CaHPO(4)) were separately irradiated, and the cements were produced with the use of irradiated powder and nonirradiated powder. Although the wet DTS value of AC produced from irradiated TTCP and nonirradiated DCPA decreased with increasing gamma irradiation dose, there was no significant difference. In contrast, the wet DTS value of AC produced from irradiated DCPA and nonirradiated TTCP significantly decreased with the increase in gamma irradiation dose. In conclusion, although the detailed mechanism of the delayed setting time and decreased DTS value was not clarified by the present study, it was found that gamma irradiation affected DCPA more than TTCP.