Subunit vaccines with a saponin-based adjuvant boost humoral and cellular immunity to MERS coronavirus.

Middle East respiratory syndrome coronavirus (MERS-CoV) outbreaks have constituted a public health issue with drastic mortality higher than 34%, necessitating the development of an effective vaccine. During MERS-CoV infection, the trimeric spike protein on the viral envelope is primarily responsible for attachment to host cellular receptor, dipeptidyl peptidase 4 (DPP4). With the goal of generating a protein-based prophylactic, we designed a subunit vaccine comprising the recombinant S1 protein with a trimerization motif (S1-Fd) and examined its immunogenicity and protective immune responses in combination with various adjuvants. We found that sera from immunized wild-type and human DPP4 transgenic mice contained S1-specific antibodies that can neutralize MERS-CoV infection in susceptible cells. Vaccination with S1-Fd protein in combination with a saponin-based QS-21 adjuvant provided long-term humoral as well as cellular immunity in mice. Our findings highlight the significance of the trimeric S1 protein in the development of MERS-CoV vaccines and offer a suitable adjuvant, QS-21, to induce robust and prolonged memory T cell response.

Bioavailability and foam cells permeability enhancement of Salvianolic acid B pellets based on drug-phospholipids complex technique.

This study investigated phospholipids complex (PC) loaded pellets of poorly permeable Salvianolic acid B (SalB), in which PC was to improve the liposolubility and permeability of SalB. Transmission electron microscopy observation, differential scanning calorimetry measurement, infrared spectroscopy analysis, n-octanol/water partition coefficient study, and foam cell permeability research were employed to prove the complex formation. Pellets containing SalB phospholipids complex (SalB-PC) were prepared via extrusion/spheronization technique. The optimal pellets obtained with 30% SalB-PC, 15% Kollidon®CL-SF, 15% Flowlac®100, and 40% MCC exhibited a very homogeneous size distribution, the shortest disintegration time, highest crushing force, appreciable spherical shape, and a fast drug release behavior. Following hydration, the droplet size distribution of SalB-PC pellets was nearly same to its PC (85.4±16 and 73.5±12nm). In vivo performance showed SalB-PC pellets presented significantly larger AUC(0-)(t), which was 0.58 times more than that of physical mixtures (PMs) and 1.57 times more than that of SalB pellets. C(max) of SalB-PC pellets were also increased by 0.26-fold and 0.80-fold as that of PMs and SalB pellets, respectively. In conclusion, extrusion/spheronization could be a suitable technique to prepare PC loaded pellets, which could effectively preserve the properties of PC to improve the permeability and bioavailability of highly water-soluble drug.

Novel Tanshinone II A ternary solid dispersion pellets prepared by a single-step technique: in vitro and in vivo evaluation.

Novel Tanshinone II A (TA) ternary solid dispersion (tSD) pellets with the combination of polyvinylpyrrolidone and poloxamer 188 as dispersing carriers were prepared by a single-step technique. A formulation screening study showed that the addition of poloxamer 188 to binary TA-PVP system could remarkably promote the dissolution rate of TA from 60% to 100% after 60 min. Scanning electron microscopy study revealed a smooth surface and a tightly packed coating structure. Differential scanning calorimetry analysis confirmed the formation of solid dispersions. In vivo test showed that TA tSD pellets presented significantly larger AUC(0-)(t), which was 0.76 times more than that of binary solid dispersion (bSD) pellets, 2.87 times more than that of physical mixtures (PMs) and 5.40 times more than that of TA. C(max) of TA tSD pellets also increased by 1.82-8.97-fold as that of bSD pellets, PMs and TA. TA tSD pellets generated obviously shortened T(max) of (3.80 ± 0.398)h, compared to bSD pellets with (4.15 ± 0.456)h, PMs with (4.65 ± 0.226)h and TA with (5.52 ± 0.738)h. In conclusion, the addition of poloxamer 188 to pellets containing PVP-based solid dispersions could achieve complete dissolution, accelerated absorption rate and superior oral bioavailability. The fluid-bed technique becomes an alternative approach to obtain solid dispersion-coated pellets.