Preparation of Lung Targeting Microspheres of Gelatin Ceftiofur Alkali

Gelatin ceftiofur alkali microsphere was prepared to observe its characteristics and evaluate preservation conditions. The glutaraldehyde was increased and the carboxylic methyl chitosan was added to improve the microsphere. The experimental results show microspheres have a better morphology surface and fairly regular structure with 4% glutaraldehyde. The average particle size is 15.84 gm and particle size distribution is narrow which shows a good uniformity. Microsphere size was affected by the stirrer speed, dosing ratio and curing degree. The greater drug loaded is, the better microspheres loading is; but with the increase of drug loading rate, the entrapment efficiency increases first and then decreases. The drug release rate of the microsphere is 24.90% in 0.5 h and 84.90% in 48 h, when CMC-GMs with 4% curing agent is 32.03% in 0.5 h and 88.44% in 48 h. So Gms embedding of ceftiofur alkali are better than CMC-GM. The stability tests show that strong light, high temperature, high humidity have a great influence on the microspheres.

Preparation of PLGA Ceftiofur Hydrochlorate Lung- targeted Microsphere with Spray Drying Process

To explore the preparation of PLGA ceftiofur hydrochlorate lung-targeted microsphere with spray drying process, the preparation technics was optimized by orthogonal experiments. Appearance, particle size, drug-loaded properties and medicine dissolution rate of the microsphere were evaluated. The experimental results show that the prepared PLGA microspheres loaded with ceftiofur hydrochlorate have good appearance, good encapsulate rate and dissolution. The drug loading capacity of ceftiofur-hydrochlorate-loaded PLGA microsphere prepared with spray drying process is 23.06%, i e, when the dosing ratio is 1：3, the encapsulate rate is 92.23% at maximum, and the release percentage of medicine is at 0.5 h. The medicine is released almost completely at 20 h and the accumulated medicine release is 98.12%.

Cancer cell membrane-coated bacterial ghosts for highly efficient paclitaxel delivery against metastatic lung cancer

Chemotherapy is one of the major approaches for the treatment of metastatic lung cancer,although it is limited by the low tumor delivery efficacy of anticancer drugs.Bacterial therapy is emerging for cancer treatment due to its high immune stimulation effect;however,excessively generated immunogenicity will cause serious inflammatory response syndrome.Here,we prepared cancer cell membrane-coated liposomal paclitaxel-loaded bacterial ghosts(LP@BG@CCM)by layer-by-layer encapsulation for the treatment of metastatic lung cancer.The preparation processes were simple,only involving film formation,electroporation,and pore extrusion.LP@BG@CCM owned much higher 4T1 cancer cell toxicity than LP@BG due to its faster fusion with cancer cells.In the 4T1 breast cancer metastatic lung cancer mouse models,the remarkably higher lung targeting of intravenously injected LP@BG@CCM was observed with the almost normalized lung appearance,the reduced lung weight,the clear lung tissue structure,and the enhanced cancer cell apoptosis compared to its precursors.Moreover,several major immune factors were improved after administration of LP@BG@CCM,including the CD4^(+)/CD8a^(+)T cells in the spleen and the TNF-α,IFN-γ,and IL-4 in the lung.LP@BG@CCM exhibits the optimal synergistic chemo-immunotherapy,which is a promising medication for the treatment of metastatic lung cancer.

Efficacy of Aidi Injection(艾迪注射液)on Overexpression of P-Glycoprotein Induced by Vinorelbine and Cisplatin Regimen in Patients with Non-Small Cell Lung Cancer

Objective：To investigate the efficacy of Aidi Injection（艾迪注射液） on overexpression of P-glycoprotein（P-gp） induced by vinorelbine and cisplatin（NP） regimen in patients with non-small cell lung cancer（NSCLC）, and study the difference between intravenous administration and targeting intratumor administration of Aidi Injection with thoracoscope. Methods：Totally 150 patients with NSCLC were randomly assigned to the control group, the intravenous group and the intratumor group by the random envelope method, 50 cases in each group. The patients were treated with NP regimen（2 cycles）, NP regimen（2 cycles） plus Aidi intravenous injection, or NP regimen（2 cycles） plus Aidi intratumor injection with thoracoscope, respectively for 6 weeks. The clinical efficacy was observed based on Response Evaluation Criteria in Solid Tumors（RECIST） rules, the expression of P-gp in the tumor tissue was tested before, 3 and 6 weeks after treatment, the safety was evaluated by monitoring the toxicity in the process of treatment, and the progressionfree survival（PFS） was measured. Results：Fifteen cases dropped out because of the irreconcilable conditions which had no relationship with the treatment, 4 in the control group, 5 in the intravenous group, and 6 in the intratumor group, respectively. Compared with the control group, the response rates（complete remission ＋ partial response） and the disease control rates（complete remission ＋ partial response ＋ stable disease） were significantly higher, the P-gp expressions were significantly decreased after 3 and 6 weeks of treatment, and the Kaplan-Meier survival curves of PFS were significantly longer in the intravenous and intratumor groups（P〈0.05 or P〈0.01）, and the intratumor group showed better effects than the intravenous group（P〈0.05 or P〈0.01）. Compared with the control group, the occurrences of rash, nausea and leukocytopenia were significantly decreased in the intravenous and intratumor groups（P〈0.05）, but without significant difference between the intravenous and intratumor groups（P〉0.05）. Conclusion：Aidi Injection not only improves the efficacy of NP regime, but also has the function of reducing adverse events and preventing against overexpression of P-gp induced by chemotherapy of NP regimen.

A micro-sized vaccine based on recombinant Lactiplantibacillus plantarum fights against SARS-CoV-2 infection via intranasal immunization

COVID-19 has globally spread to burden the medical system.Even with a massive vaccination,a mucosal vaccine offering more comprehensive and convenient protection is imminent.Here,a micro-sized vaccine based on recombinant Lactiplantibacillus plantarum(rLP)displaying spike or receptor-binding domain(RBD)was characterized as microparticles,and its safety and protective effects against SARS-CoV-2 were evaluated.We found a 66.7%mortality reduction and 100%protection with rLP against SARS-CoV-2 in a mouse model.The histological analysis showed decreased hemorrhage symptoms and increased leukocyte infiltration in the lung.Especially,rLP:RBD significantly decreased pulmonary viral loads.For the first time,our study provides a L.plantarum-vectored vaccine to prevent COVID-19 progress and transmission via intranasal vaccination.