ABSTRACT
To assess the virucidal effect of povidone iodine (PVP-I) on severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) located in the nasopharynx and suitable dose-formulation for nasal application were the purpose of this clinical trial. This single-center, open-label randomized clinical trial with a 7-arm parallel-group design was conducted in Dhaka Medical College (DMC) Hospital. A total of 189 reverse transcription-polymerase chain reaction (RT-PCR)-confirmed SARS CoV-2 positive cases aged 12-90 years with symptoms was sequentially enrolled following randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested against PVP-I nasal irrigation (NI) at diluted concentrations of 0.4%, 0.5% and 0.6%, and PVP-I nasal spray (NS) at diluted concentrations of 0.5% and 0.6%. All groups were compared to the corresponding controls (distilled water). Written informed consent was ensured before participation. All procedures were conducted in after ethical clearance from the Ethical Review Board and in accordance with the Declaration of Helsinki. Viral clearance in a repeat RT-PCR (qualitative) was the primary outcome, and occurrence of any adverse event following administration of testing drug was considered as the secondary outcome. Analysis was performed using SPSS (Version 26). All cases were randomized into seven groups and each group consists of 27-patient. Mean age of the cases 43.98 ± 12.67 years (SD). All strength of NI were effective in nasopharyngeal clearance compared to the control (0.4%, p = 0.006; 0.5%, p < 0.001; and 0.6%, p = 0.018). Similarly, all strength of the NS is also effective than control (0.5%, p = < 0.001; and 0.6%, p ≤ 0.001). Highest nasopharyngeal clearance was observed in patients using 0.5% NI (n = 25, 92.6%, p = 0.018). Nasal irritation was the single most adverse event recorded in this trial and found in two patients using 0.4%, and 0.6% PVP-I NI, respectively. Both PVP-I NS and NI are effective for nasopharyngeal clearance in-vivo. However, further community trials are needed to repurpose these solutions as preventive agents against SARS-CoV2. Ethical clearance memo no ERC-DMC/ECC/2020/93. Trial registration NCT Identifier number NCT04549376. Supplementary Information: The online version contains supplementary material available at 10.1007/s12070-022-03106-0.
ABSTRACT
Povidone-iodine (PVP-I) is a time-tested antiseptic agent with excellent virucidal (99.99%) properties. Repurposing it against coronavirus disease-19 (COVID-19) is a relatively newer concept and has been sparsely tested in vivo. The most common route of entry of severe acute respiratory syndrome coronavirus 2 (SARS CoV-2) is the nasopharynx. Averting colonization of the virus could be one of the best options to reduce the incidence of infection. PVP-I gargle and mouthwash were found to be effective in vitro rapid inactivation against SARS-CoV-2 on a smaller scale (Hassandarvish et al. in BDJ 1-4, 2020, Pelletier et al. in ENTJ 1-5, 2020). However, efficacy in humans is lacking. To assess the virucidal effect of PVP-I against SARS-CoV-2 located in the nasopharynx was the objective of this parallel armed randomized clinical trial. We screened all RT-PCR-confirmed COVID-19 cases aged 18 years and above with symptoms. Written informed consent was obtained before randomization. Nasopharyngeal clearance of SARS-CoV-2 was tested after single time application of PVP-I nasal irrigation (NI) at diluted concentrations of .4%, .5% and .6% and PVP-I nasal spray (NS) at diluted concentrations of .5% and .6%. All groups were compared to the corresponding controls (distilled water). The primary outcome was viral clearance in a repeat RT-PCR (qualitative), and the secondary outcome was the number of adverse events. Final data analysis was performed using the statistical software SPSS (Version 20). A total of 189 confirmed COVID-19 cases were randomized into seven groups: 27 patients in each group. Of all, 159 (84.1%) were male, and 30 (15.9%) were female. We observed a statistically significant proportion of nasopharyngeal clearance with all strengths of PVP-I NI and PVP-I NS compared to the corresponding controls. Additionally, 0.5% NI was significantly better than 0.5% NS for viral clearance (p = 0.018) and had the highest nasopharyngeal clearance among all strengths (n = 25, 92.6%). 0.6% NS is better than CNS and 0.5%NS in viral clearance. The only adverse event was nasal irritation recorded in two patients each in the 0.4% and 0.6% PVP-I NI groups (Tables 1 and 2). PVP-I NI and NS are proved as effective virucidal agent against SARS-CoV-2 in human body. Our recommendation is to use PVP-I in naopharynx (as well as oropharynx) to prevent COVID-19.
ABSTRACT
Inorganic nanoparticles hold great potential in the area of precision medicine, particularly for treating cancer owing to their unique physicochemical properties, biocompatibility and improved pharmacokinetics properties compared to their organic counterparts. Here we introduce strontium sulfite nanoparticles as new pH-responsive inorganic nanocarriers for efficient transport of siRNAs into breast cancer cells. We employed the simplest nanoprecipitation method to generate the strontium sulfite nanoparticles (SSNs) and demonstrated the dramatic roles of NaCl and d-glucose in particle growth stabilization in order to produce even smaller nanosize particles (Na-Glc-SSN) with high affinity towards negatively charged siRNA, enabling it to efficiently enter the cancer cells. Moreover, the nanoparticles were found to be degraded with a small drop in pH, suggesting their potential capability to undergo rapid dissolution at endosomal pH so as to release the payload. While these particles were found to be nontoxic to the cells, they showed higher potency in facilitating cancer cell death through intracellular delivery and release of oncogene-specific siRNAs targeting ros1 and egfr1 mRNA transcripts, than the strontium sulfite particles prepared in absence of NaCl and d-glucose, as confirmed by growth inhibition assay. The mouse plasma binding analysis by Q-TOF LC-MS/MS demonstrated less protein binding to smaller particles of Na-Glc-SSNs. The biodistribution studies of the particles after 4 h of treatment showed Na-Glc-SSNs had less off-target distribution than SSNs, and after 24 h, all siRNAs were cleared from all major organs except the tumors. ROS1 siRNA with its potential therapeutic role in treating 4T1-induced breast tumor was selected for subsequent in vivo tumor regression study, revealing that ROS1 siRNA-loaded SSNs exerted more significant anti-tumor effects than Na-Glc-SSNs carrying the same siRNA following intravenous administration, without any systemic toxicity. Thus, strontium sulfite emerged as a powerful siRNA delivery tool with potential applications in cancer gene therapy.
