Doxorubicin-loaded phosphatidylethanolamine-conjugated nanoliposomes: in vitro characterization and their accumulation in liver, kidneys, and lungs in rats

Anandamoy Rudra, R Manasa Deepa, Miltu Kumar Ghosh, Subhajit Ghosh, Biswajit MukherjeeDepartment of Pharmaceutical Technology, Jadavpur University, Kolkata (Calcutta), IndiaIntroduction: Phosphatidylethanolamine (PE)-conjugated nanoliposomes were developed, characterized, and investigated for their accumulation in liver, kidneys, and lungs in rats.Methods: Drug-excipient interaction was studied using Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), surface morphology by field emission scanning electron microscopy, elemental analysis by energy dispersive X-ray (EDX) analysis, zeta potential and size distribution using a Zetasizer and particle size analyzer, and in vitro drug release by dialysis membrane. In vivo accumulation of liposomes in tissues was also studied.Results: No chemical reaction was observed between drug and excipients. EDX study confirmed PE-conjugation in liposomes. Doxorubicin-loaded liposomes (DOX-L) and PE-conjugated doxorubicin-loaded liposomes (DOX-PEL) were of smooth surface and homogenously distributed in nanosize range (32–37 nm) with a negative surface charge. Loading efficiencies were 49.25% ± 1.05% and 52.98% ± 3.22% respectively, for DOX-L and DOX-PEL. In vitro drug release study showed 69.91% ± 1.05% and 77.07% ± 1.02% doxorubicin released, from DOX-L and DOX-PEL, respectively, in nine hours. Fluorescence microscopic study showed that liposomes were well distributed in liver, lungs, and kidneys.Conclusion: Data suggests that PE-conjugated nanoliposomes released the drug in a sustained manner and were capable of distributing them in various organs. This may be used for cell/ tissue targeting, attaching specific antibodies to PE.Keywords: doxorubicin, phosphatidylethanolamine-conjugated nanoliposomes, tissue accumulatio

Clinical Characterization and Genomic Analysis of Samples from COVID-19 Breakthrough Infections during the Second Wave among the Various States of India

From March to June 2021, India experienced a deadly second wave of COVID-19, with an increased number of post-vaccination breakthrough infections reported across the country. To understand the possible reason for these breakthroughs, we collected 677 clinical samples (throat swab/nasal swabs) of individuals from 17 states/Union Territories of the country who had received two doses (n = 592) and one dose (n = 85) of vaccines and tested positive for COVID-19. These cases were telephonically interviewed and clinical data were analyzed. A total of 511 SARS-CoV-2 genomes were recovered with genome coverage of higher than 98% from both groups. Analysis of both groups determined that 86.69% (n = 443) of them belonged to the Delta variant, along with Alpha, Kappa, Delta AY.1, and Delta AY.2. The Delta variant clustered into four distinct sub-lineages. Sub-lineage I had mutations in ORF1ab A1306S, P2046L, P2287S, V2930L, T3255I, T3446A, G5063S, P5401L, and A6319V, and in N G215C; Sub-lineage II had mutations in ORF1ab P309L, A3209V, V3718A, G5063S, P5401L, and ORF7a L116F; Sub-lineage III had mutations in ORF1ab A3209V, V3718A, T3750I, G5063S, and P5401L and in spike A222V; Sub-lineage IV had mutations in ORF1ab P309L, D2980N, and F3138S and spike K77T. This study indicates that majority of the breakthrough COVID-19 clinical cases were infected with the Delta variant, and only 9.8% cases required hospitalization, while fatality was observed in only 0.4% cases. This clearly suggests that the vaccination does provide reduction in hospital admission and mortality

Congenital rubella syndrome surveillance in India, 2016–21: Analysis of five years surveillance data

Background: In India, facility-based surveillance for congenital rubella syndrome (CRS) was initiated in 2016 to estimate the burden and monitor the progress made in rubella control. We analyzed the surveillance data for 2016–2021 from 14 sentinel sites to describe the epidemiology of CRS. Method: We analyzed the surveillance data to describe the distribution of suspected and laboratory confirmed CRS patients by time, place and person characteristics. We compared clinical signs of laboratory confirmed CRS and discarded case-patients to find independent predictors of CRS using logistic regression analysis and developed a risk prediction model. Results: During 2016–21, surveillance sites enrolled 3940 suspected CRS case-patients (Age 3.5 months, SD: 3.5). About one-fifth (n = 813, 20.6%) were enrolled during newborn examination. Of the suspected CRS patients, 493 (12.5%) had laboratory evidence of rubella infection. The proportion of laboratory confirmed CRS cases declined from 26% in 2017 to 8.7% in 2021. Laboratory confirmed patients had higher odds of having hearing impairment (Odds ratio [OR] = 9.5, 95% confidence interval [CI]: 5.6–16.2), cataract (OR = 7.8, 95% CI: 5.4–11.2), pigmentary retinopathy (OR = 6.7, 95 CI: 3.3–13.6), structural heart defect with hearing impairment (OR = 3.8, 95% CI: 1.2–12.2) and glaucoma (OR = 3.1, 95% CI: 1.2–8.1). Nomogram, along with a web version, was developed. Conclusions: Rubella continues to be a significant public health issue in India. The declining trend of test positivity among suspected CRS case-patients needs to be monitored through continued surveillance in these sentinel sites