Purpose: Spray-freeze drying (SFD) is a recently applied method to develop pharmaceutical powders. This study aimed to analyze the competence of Trehalose, Mannitol, Lactose, and Sorbitol instability and aerosolization of Immunoglobulin G (IgG) via SFD.
Methods: Induced soluble aggregates were quantified at 0 and 3?months, and 45?°C using size-exclusion chromatography. Conformation and thermogravimetric assessments were done by Fourier transform infrared spectroscopy and differential scanning calorimetry. Laser light scattering was performed to determine the particle sizes. Aerodynamic features were characterized by twin stage impinger and scanning electron microscopy.
Results: Although sugars/polyols preferably stabilized IgG following the process, storage stabilization was achieved in Trehalose, Trehalose-Lactose, Lactose, and Trehalose-Mannitol-based powders with soluble aggregates <5%. The conformation of antibody was preserved with β sheet content from 66.28% to 76.37%. Particle sizes ranged from 5.23 to 8.12?µm. Mannitol exhibited the best aerodynamic behavior, fine particle fraction (FPF: 70%) but high degree of protein aggregation during storage.
Conclusions: SFD could favorably stabilize antibody using Trehalose and its combination with Lactose and Mannitol, and also, Lactose alone. Sorbitol disturbed IgG powder recovery. Incorporation of other types of excipient is required for efficient respiratory delivery of IgG molecules. 相似文献
We describe the preclinical development of a dengue virus vaccine targeting the dengue virus serotype 2 (DENV2) envelope domain III (EDIII). This study provides proof-of-principle that a dengue EDIII protein scaffold/DNA vaccine can protect against dengue challenge. The dengue vaccine (EDIII-E2) is composed of both a protein particle and a DNA expression plasmid delivered simultaneously via intramuscular injection (protein) and gene gun (DNA) into rhesus macaques. The protein component can contain a maximum of 60 copies of EDIII presented on a multimeric scaffold of Geobacillus stearothermophilus E2 proteins. The DNA component is composed of the EDIII portion of the envelope gene cloned into an expression plasmid. The EDIII-E2 vaccine elicited robust antibody responses to DENV2, with neutralizing antibody responses detectable following the first boost and reaching titers of greater than 1:100,000 following the second and final boost. Vaccinated and naïve groups of macaques were challenged with DENV2. All vaccinated macaques were protected from detectable viremia by infectious assay, while naïve animals had detectable viremia for 2–7 days post-challenge. All naïve macaques had detectable viral RNA from day 2–10 post-challenge. In the EDIII-E2 group, three macaques were negative for viral RNA and three were found to have detectable viral RNA post challenge. Viremia onset was delayed and the duration was shortened relative to naïve controls. The presence of viral RNA post-challenge corresponded to a 10–30-fold boost in neutralization titers 28 days post challenge, whereas no boost was observed in the fully protected animals. Based on these results, we determine that pre-challenge 50% neutralization titers of >1:6000 correlated with sterilizing protection against DENV2 challenge in EDIII-E2 vaccinated macaques. Identification of the critical correlate of protection for the EDIII-E2 platform in the robust non-human primate model lays the groundwork for further development of a tetravalent EDIII-E2 dengue vaccine. 相似文献
IntroductionThe liver is the most frequently damaged organ in blunt abdominal trauma. It is widely accepted that hemodynamically stable patients with low-grade liver trauma should be treated with non-operative management, however there is controversy surrounding its safety and efficacy in high-grade trauma. The purpose of this review is to investigate the role of non-operative management in patients with high-grade liver trauma.MethodsPubMed and reference lists of PubMed articles were searched to find studies that examined the efficacy of non-operative management in high-grade liver injury patients, and compare it to operative management. Non-operative management was considered successful if rescue surgery was avoided. Outcomes considered were success, mortality, and complication rates.ResultsThe electronic search revealed 2662 records, 8 of which met the inclusion criteria. All 8 studies contained results suggesting that non-operative management was safe and effective in hemodynamically stable patients with high-grade liver trauma. By combining the outcomes of the different studies, non-operative management had a high success rate of 92.4% (194/210) in high-grade liver trauma patients, which was near the overall 95.0% non-operative management success rate. Non-operative management also had mortality and complication rates of 4.6% (9/194) and 9.7% (7/72) in high-grade injury patients, respectively, compared to operative management's 17.6% (26/148) and 45.5% (5/11).ConclusionNon-operative management of liver trauma is safe and effective in hemodynamically stable patients with high-grade liver injury. It is associated with significantly lower mortality compared with operative management. More studies are required to evaluate complications of non-operative management in high-grade liver injury. 相似文献
Hydroxylation is the predominant pathway of metabolism for sulfatroxazole in the body, accounting for 70 per cent of the dose. Fifteen per cent of the dose is acetylated unimodally and 10 per cent is excreted unchanged. The half-lives of sulfatroxazole and its metabolites 5-hydroxysulfatroxazole and N4-acetylsulfatroxazole are approximately 22 h after administration of sulfatroxazole. N4-acetylsulfatroxazole, taken as parent drug, is eliminated by renal excretion (92 per cent of the dose). The initial elimination half-life of N4-acetylsulfatroxazole is 4.5 h, which later increases to 70 h as the result of the acetylation-deacetylation equilibrium. Probenecid inhibits the renal excretion of the metabolites 5-hydroxy- and N4-acetylsulfatroxazole. Inhibition of the N4-acetyl metabolite favours the deacetylation, which results in an increase of the T 1/2 of sulfatroxazole from 20 to 30 h. The protein binding value of sulfatroxazole is 84 per cent, that of N4-acetylsulfatroxazole is 37 per cent. Sulfatroxazole is excreted renally by passive processes, while the metabolites are excreted by both passive and active processes. 相似文献
PURPOSE: The purpose of this study was to measure spectrophotometrically the color stability of pigmented A-2186 silicone maxillofacial elastomer with 10% by volume of titanium white dry earth opacifier before and after exposure to microwave energy over a simulated 1.5-year period of microwave sterilization. Materials AND METHODS: A-2186 silicone elastomer opacified with titanium white dry earth pigment, pigmented with 5 cosmetic dry earth pigment colors [no pigment (control) group (Pc), red (Pr), yellow ochre (Py), burnt sienna (Po), and a mixture of Pr + Py + Po color group (P3)], was used in this study. Each of the 5 experimental groups consisted of 5 specimens. All specimens were placed in a 250 ml glass beaker filled with 150 ml of water (replenished for each microwave exposure). An exposure of 6 minutes was used 18 times (simulating 1.5 years of microwave sterilization with one 6 minute exposure monthly). Reflectance values were measured by spectrophotometer. Three- and two-way analyses of variance with repeated measures were performed for the color difference (DeltaE*) with the factors of group/color/months, and group/months, respectively. Means were compared by Tukey Honest Significant Difference (HSD) multiple range test calculated at the 0.05 level of significance using SPSS. RESULTS: The trained human eye can detect color changes (DeltaE*) greater than 1.0. Most DeltaE* values of the red pigment group at all intervals and the mixed pigment group at 15- and 18- month intervals increased significantly greater than 1.0 (p < 0.001) compared with the control group. Yellow and burnt sienna groups remained the most color stable over time with DeltaE* values below 0.35. CONCLUSIONS: Lack of color stability of red dry earth pigmented A-2186 silicone maxillofacial elastomers was clinically significant after 12-month exposure to microwave energy as compared with yellow, burnt sienna, and opacified A-2186 dry earth pigments. 相似文献