| Background: Long-term inhalation corticosteroids are crucial for preventing reliving-stage asthmatic patients from acute attacking. In order to avoid the potential side-effects which caused by inhalation corticosteroid for long term or high dose, it is essential to develop a novel inhaled corticosteroid preparation with sustained releasing and good target in asthma clinical therapy.Objectives: (1) To characterize the kinetics of beclomethasone prcpionate (BDP) nano-capsule in vivo. (2) To explore the allergic reaction of BDP-polylactate-polyglycolic acid copolymer (PLGA) nano-capsules in healthy guinea pigs and therapeutic action in guinea pig asthmatic models. (3) To evaluate the effect of inhaled BDP nano-capsule on soluble intercellular adhesion molecule-1 (ICMA-1) in bronchoalveolar lavage fluid (BALF) and plasma, cellular surface adhesion molecule of cell-deposit in BALF so try to discover the anti-inflammatory mechanism of BDP-PLGA nano-capsules.Methods: (1) With the PLGA as matrix and ultrasound emulsification and dissolvent volatilization, PLGA nano-encapsuled BDP of nanoparticals(NP) were prepared. BDP-PLGA nano-capsules were administered to healthy guinea pigs after tracheal intubation. Blood and lung tissues were harvested at different time-points and BDP concentrations were detected in guinea pig's plasma and lung tissue homogenates by high press liquidchromatography (HPLC). (2) The allergic experiment in healthy guinea pigs was performed after administration BDP-PLGA nano-capsules by ultra-abdominal injection and oral spray. Asthmatic symptom grades, cell classified counts of blood and BLAF were recorded after different doses BDP-PLGA nano-capsules inhalation in guinea pigs asthmatic model. (3) The optical density (OD) values of soluble intercellular adhesion molecule l(sICMA-l) in BALF and plasma were measured by indirect enzyme linked immunosorbent assay (ELISA); Cellular surface adhesion molecule of cell-deposit in BLAF was observed by double-antigen fluorescence immunograpy after inhaled BDP-PLGA nano-capsules inhalation.Results: (1) The features of BDP-PLGA nano-capsules were described as smooth surface and average diameter 126.4nm with normal distribution, the rate of earring BDP is 36.4%?.07% . In lung tissue homogenates, the peak concentration of BDP of conventional BDP group was present at about 8 hours after administration and then descended rapidly by HPLC detection. In contrast, the releasing BDP of BDP-PLGA nano-capsules in vivo complied with double-room kinetics: there was relatively rapid blast-releasing at 0.5-1.0 hour, peaked at about 8 hours, followed by a high plateau up to 72 hours. Compared with BDP-PLGA nano-capsule group, the BDP level in conventional BDP group was obviously lower since 12 h after inhalation. Moreover, in guinea pig's plasma, BDP concentrations were not detected in both BDP conventional preparation and BDP-PLGA nano-capsule. (2) It was demonstrated that there was no allergy in vivo. There was no significant difference in asthmatic symptom grades after treatment with BDP-PLGA nano-capsules inhaled every 3 days and BDP inhaled once every day respectively at the same total dose, but there was discrepancy between BDP-PLGA nano-capsules high-dose and low-dose therapy groups (P<0.05). Under the same-dose circumstances, there was no discrepancy in the total numberof leukocyte (the total number of cell in BALF), lymphocyte, eosinophil and neutrophil counts between BDP-PLGA nano-capsules and BDP conventional group in blood and BALF, but compared with asthma model group, there was significant difference (P<0.05). It was demonstrated that the inflammation in bronchial and lung tissues was distinctly improved in BDP-PLGA nano-capsules therapy group in pathological sections, especially eosinophil migration remarkable decreasing. (3) The OD values of soluble intercellular adhesion molecule l(sICMA-l) in BLAF and plasma of BDP-PLGA nano-capsule therapy group were significantly lower than asthma model group (P<0.05), but compared with BDP therapy group, the... |
PDF Full Text Request