The great potential of hydroxypropyl beta-cyclodextrin (HPßCD), as a dried-protein stabilizer, has been attributed to various mechanisms namely water-replacement, vitrification and surfactant-like effects. Highlighting the best result in our previous study (weight ratio IgG: HPßCD of 1:0.4), herein we designed to evaluate the efficacy of upper (1:2) and lower (1:0.05) ratios of HPßCD in stabilization and aerosol properties of spray freeze-dried IgG. The protective effect of HPβCD, as measured by size exclusion chromatography (SEC-HPLC) was most pronounced at C3′ and C3″, IgG:trehalose:HPβCD ratios of 1:2:0.25 and 1:2:0.05 with aggregation rate constants of 0.46 ± 0.02 and 0.58 ± 0.01 (1/month), respectively. The secondary conformations were analyzed through Fourier transform infrared spectroscopy (FTIR) and all powders well-preserved with the lack of any visible fragments qualified through sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PPAGE). Scanning electron microscopy (SEM) and twin stage impinger (TSI) were employed to characterize the suitability of particles for further inhalation therapy of antibodies and the highest values of fine particle fraction (FPF) were achieved by C3′ and C3″, 56.43 and 48.12%. The powders produced at the current ratio 1:2:0.25 and 1:2:0.05 are superior to our previous examination with regards to manifesting lower aggregation and comparable FPF values.

Several vaccine-induced thrombotic thrombocytopenia syndrome (VITTS) cases have been reported after the ChAdOx1 nCov-19 vaccination. The current study systematically reviewed the reported post-ChAdOx1 nCoV-19 vaccination thrombotic thrombocytopenia cases. Their laboratory and clinical features, as well as the diagnostic and therapeutic measures, were investigated. Online databases were searched until 25 August 2021. Studies reporting post-ChAdOx1 nCov-19 vaccination thrombotic thrombocytopenia syndrome (TTS) were included. Overall, 167 cases (21-77 years old) from 53 publications were included showing a female dominance of 1.75 times. About 85% of the cases exhibited the primary symptoms within the first two weeks post-vaccination. Headache was the most common initial symptom (>44.2%), and hemorrhage/thrombotic problems (22.46%), as well as discoordination/weakness/numbness/ hemiparesis/cyanotic toes (19.6%), were the most prevalent uncommon initial symptoms. Prothrombin time (PT), D-dimers, and C-reactive protein were the most remarkable increased laboratory parameters in 50.6%, 99.1%, and 55.6% of cases, respectively. In comparison, platelet and fibrinogen were the most remarkable decreased laboratory parameters in 92.7% and 50.5% of cases, respectively. Most VITT cases presented with cerebral venous thrombosis/cerebral venous sinus thrombosis, supraventricular tachycardia, transverse sinus/cerebral thrombosis, pulmonary embolism, and cerebral hemorrhage. Anti-PF4 antibody measurement through immunoassays and functional assays were positive in 86.2% and 73% of cases, respectively. About 31% of the cases died. Early diagnosis and proper therapeutic measures are important in ChAdOx1 nCov-19 vaccine-induced VITTS patients. Therefore, experts are recommended to know the corresponding clinical and laboratory features, as well as diagnostic methods. Elucidation of the pathophysiologic mechanism of ChAdOx1 nCov-19 vaccine-induced TTS deserves further investigation.