Infectious Disease Modeling with Socio-Viral Behavioral Aspects-Lessons Learned from the Spread of SARS-CoV-2 in a University.

When it comes to understanding the spread of COVID-19, recent studies have shown that pathogens can be transmitted in two ways: direct contact and airborne pathogens. While the former is strongly related to the distancing behavior of people in society, the latter are associated with the length of the period in which the airborne pathogens remain active. Considering those facts, we constructed a compartmental model with a time-dependent transmission rate that incorporates the two sources of infection. This paper provides an analytical and numerical study of the model that validates trivial insights related to disease spread in a responsive society. As a case study, we applied the model to the COVID-19 spread data from a university environment, namely, the Institut Teknologi Bandung, Indonesia, during its early reopening stage, with a constant number of students. The results show a significant fit between the rendered model and the recorded cases of infections. The extrapolated trajectories indicate the resurgence of cases as students' interaction distance approaches its natural level. The assessment of several strategies is undertaken in this study in order to assist with the school reopening process.

Comparative Bioavailability Study of Solid Self-Nanoemulsifying Drug Delivery System of Fenofibric Acid in Healthy Male Subjects.

OBJECTIVE: This study aimed to evaluate the effect of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formation on the bioavailability of fenofibric acid. SUBJECT AND METHODS: Three formulations of fenofibric acid, namely, S-SNEDDS containing medium-chain triglyceride (FS1), S-SNEDDS containing long-chain triglyceride (FS2), and FSt as tablet of innovator product, were used in this study. Bioavailability study was conducted in 12 Indonesian healthy male subjects after a single-dose administration of each formulation with three-way crossover design. Blood samples were collected from 0 to 72 h after drug administration and then analyzed using the high-performance liquid chromatography method. Data were statistically analyzed using the ANOVA and the Wilcoxon signed-rank test using a p value of 0.05. Dissolution test was carried out with USP dissolution apparatus using three medium (pH 1.2, 4.5 and 6.8). RESULTS: The rates of absorption of fenofibric acid from S-SNEDDS FS1 and FS2 were significantly increased about 1.78 and 2.40 times, respectively, relative to FSt. Tmax values of FS1 and FS2 were shorter than FSt, namely, 0.96 ± 0.438 h (FS1), 0.71 ± 0.445 h (FS2), and 1.71 ± 0.840 h (FSt), respectively. Meanwhile, the Cmax and AUC values of FS1, FS2, and FSt were found to be not significantly different with a p value of >0.05. S-SNEDDS formation increased the dissolution rate in acid medium. CONCLUSIONS: S-SNEDDS increased the dissolution rate in acid medium and absorption rate of fenofibric acid but did not increase the extent of fenofibric acid absorption.

A Novel Desloratadine-Benzoic Acid Co-Amorphous Solid: Preparation, Characterization, and Stability Evaluation.

Low physical stability is the limitation of the widespread use of amorphous drugs. The co-amorphous drug system is a new and emerging method for preparing a stable amorphous form. Co-amorphous is a single-phase amorphous multicomponent system consisting of two or more small molecules that are a combination of drugs or drugs and excipients. The co-amorphous system that uses benzoic acid (BA) as an excipient was studied to improve the physical stability, dissolution, and solubility of desloratadine (DES). In this study, the co-amorphous formation of DES and BA (DES⁻BA) was prepared by melt-quenching method and characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (PXRD), and polarized light microscopy (PLM). Dissolution, solubility, and physical stability profiles of DES⁻BA were determined. The DES crystals were converted into DES⁻BA co-amorphous form to reveal the molecular interactions between DES and BA. Solid-state analysis proved that the co-amorphous DES⁻BA system (1:1) is amorphous and homogeneous. The DSC experiment showed that the glass transition temperature (Tg) of tested DES⁻BA co-amorphous had a higher single Tg compared to the amorphous DES. FTIR revealed strong interactions, especially salt formation. The dissolution rate and solubility of co-amorphous DES⁻BA (1:1) obtained were larger than the DES in crystalline form. The PXRD technique was used to assess physical stability for three months at 40 °C with 75% RH. The DES⁻BA co-amorphous system demonstrated better physical stability than a single form of amorphous DES. Co-amorphous DES⁻BA has demonstrated the potential for improving solid-state stability, as the formation of DES⁻BA co-amorphous salt increased solubility and dissolution when compared to pure crystalline DES. This study also demonstrated the possibility for developing a DES⁻BA co-amorphous system toward oral formulations to improve DES solubility and bioavailability.

Synthesis, characterization, and stability study of desloratadine multicomponent crystal formation.

This study describes the formation of multicomponent crystal (MCC) of desloratadine (DES). The objective of this study was to discover the new pharmaceutical MCC of DES using several coformers. The MCC synthesis was performed between DES and 26 coformers using an equimolar ratio with a solvent evaporation technique. The selection of the appropriate solvent was carried out using 12 solvents. The preview of the MCC of DES was performed using polarized light microscopy (PLM). The formation of MCC was confirmed using powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The accelerated stability of MCC at 40 °C and relative humidity of 75% was investigated using PXRD and FTIR. Depending on the prior evaluation, DES and benzoic acid (BA) formed the MCC. PLM and SEM results showed that crystal habit of combination between DES and BA differed from the constituent components. Moreover, the diffractogram pattern of DES-BA was distinct from the constituent components. The DSC thermogram showed a new peak which was distinct from both constituent components. The FTIR study proved a new spectrum. All characterizations indicated that a new solid crystal was formed, ensuring the MCC formation. In addition, DES-BA MCC had both chemical and physical stabilities for a period of 4 months.

Improving mechanical properties of desloratadine via multicomponent crystal formation.

We report the first multicomponent crystal of desloratadine, an important anti-histamine drug, with a pharmaceutically acceptable coformer of benzoic acid. The single crystal structure analysis revealed that this novel multicomponent crystal is categorized as salt due to the proton transfer from benzoic acid to the desloratadine molecule. By forming the salt multicomponent crystal, we demonstrated that the tabletability and plasticity of the multicomponent crystal was improved from the parent drug. In addition, neither capping nor lamination tendency was observed in the desloratadine-benzoic acid multicomponent crystal. The existence of a layered structure and slip planes are proposed to be associated with this improvement. The desloratadine-benzoate in this case shows an improved solubility in water and HCl 0.1N media and a better dissolution profile in water. However, the dissolution rate in HCl 0.1N media was found to be essentially indifference.

Learning from the viral journey: how to enter cells and how to overcome intracellular barriers to reach the nucleus.

Viruses deliver their genome into host cells where they subsequently replicate and multiply. A variety of relevant strategies have evolved by which viruses gain intracellular access and utilize cellular machinery for the synthesis of their genome. Therefore, the viral journey provides insight into the cell's trafficking machinery and how it can be best exploited to improve nonviral gene delivery systems. This review summarizes viral internalization pathways and intracellular trafficking of viruses, with an emphasis on the endosomal escape processes of nonenveloped viruses. Intracellular events from viral entry through nuclear delivery of the viral complementary DNA are also discussed.

A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveolar endocytic pathway.

In the present study, the cellular uptake and subsequent intracellular trafficking of liposomes was investigated, in which a novel peptide (IRQ), identified with in vivo phage display, was modified on the surface. Since the novel peptide IRQRRRR is rich in arginine, the cellular uptake mechanism was compared with octaarginine (R8)-modified liposomes, which are known to be taken up by cells via macropinocytosis. The uptake mechanism and intracellular trafficking of peptide-modified liposomes was determined by confocal laser scanning microscopy and flow cytometry analysis. Modification of the liposomal surface with the IRQ peptide (IRQ-Lip), induced internalization via a novel pathway-caveolar endocytosis-in parallel with clathrin-mediated endocytosis. Furthermore, the IRQ peptide stimulated escape from endocytic vesicles, leading to efficient gene silencing. When siRNA was condensed and encapsulated in an IRQ-modified multifunctional envelope-type nano-device (IRQ-MEND), transgene expression was reduced 52% with the fusogenic lipid, DOPE/CHEMS. This result shows that the novel IRQ can be utilized for cytoplasmic delivery of macromolecules. Moreover, the IRQ has the potential to be useful for delivery therapeutic agents to parenchymal cells via caveolar endocytosis, as this uptake pathway also plays an important role in transcytosis.

Pharmacokinetic analysis of the tissue distribution of octaarginine modified liposomes in mice.

We recently found that octaarginine modified liposomes (R8-Lip) can be efficiently internalized by cultured cells. The purpose of the present study was to quantitatively determine the effect of R8-density on the tissue distribution of R8-Lip in mice, using their clearance as an index. R8 was introduced in the form of stearylated R8 (STR-R8). The liposomes were composed of cholesterol and egg phosphatidylcholine and were labeled with [(3)H]cholesteryl hexadecyl ether. Various densities of R8 (3%, 10% and 30%) containing liposomes were prepared with a diameter of approximately 70-80 nm. The tissue distribution of R8-Lip was determined after their i.v. administration into mice and the effect of R8-density on tissue distribution was compared with uptake clearance, the calculated tissue distribution divided by the area under the blood concentration-time course. As results, R8-Lip were more rapidly eliminated from circulating blood and distributed to many tissues, especially liver depending on the R8-density. However, the tissue uptake clearance represented similar value to that of positively charge liposomes. Based on these results, we conclude that the R8-dependent increase in R8-Lip in various tissues tested indicates that positive charge, but not PTD function derived from R8 predominantly responsible for the enhancement of tissue distribution. Therefore, it is suggested that topology control of R8 is important to exhibit the PTD function.