Facilitators and barriers to the uptake of COVID-19 vaccine precaution dose among adult population: qualitative analysis across six different states of India.

Introduction: India launched the COVID-19 vaccination drive on 16th January 2021 by vaccinating the adult population above 18 years of age. This was followed by the introduction of an additional precaution dose. As on 18th October 2022, 1,02,66,96,808 (1.02 Billion) first dose and 94, 95, 39,516 (949 Million) second doses of COVID-19 vaccine were administered. However, when compared to the uptake of the primary doses, the precaution dose uptake lagged behind with only 21,75, 12,721 (217 million) doses administered. Even though, the uptake of the primary doses remained optimal, irrespective of different interventions by the Government of India, the uptake of the precaution dose remained poor. In this context, the Ministry of Health & Family Welfare wanted to understand the facilitators and Barriers for precaution dose uptake among adults so that future immunization campaigns could address these issues. Methods: An exploratory qualitative study was conducted to assess the facilitators and barriers for COVID-19 precaution dose uptake at community level across 6 different states in India. From each of the states, two districts with the highest and lowest rates of COVID-19 vaccine precaution dose uptake were selected. In each of these districts, 2 block Primary Healthcare Centres (PHCs), one with high and one with low uptake were identified. Within these block PHCs, a PHC field area with high and low precaution dose uptakes was identified. From the identified sites a minimum of four IDIs, four FGDs were conducted among the community members. KIIs of the State Immunization Officers, District Immunisation Officers, PHC Medical Officers, healthcare workers like Accredited Social Health Activist/Auxiliary Nurse Midwife were also conducted. The data was audio recorded and it was transcribed, translated and analysed using framework approach. Results: It was observed that rise in COVID-19 cases prompted the community to take the precaution dose, this along with the cost of hospitalization and the number of productive days being lost as a result of being infected resulted in vaccine uptake. The fear of non-availability of COVID-19 vaccines latter on also prompted people for vaccine uptake. While the barriers were, poor accessibility to vaccination centers, long hours of travel, poor road connectivity and lack of transportation facilities. However, the most prominent barriers observed across all study sites was that a sense of pandemic fatigue and complacency had developed both among the providers as well as the beneficiaries. Other barriers include differences in vaccination schedules and longer duration between the primary doses of some vaccines. Media was identified to be both a barrier and facilitator for Covid-19 Precaution dose uptake. Even though media played an important role in disseminating information in the beginning of the campaign, it was soon followed by the circulation of both misinformation and disinformation. Discussion: The study identified that dissemination of accurate information and community involvement at each stage of planning and implementation are crucial for the success of any campaign. Efforts should be constantly made to address and re-invent strategies that will be most suitable for the needs of the community. Therefore, in order to ensure successful vaccination campaigns, it is crucial that along with political will it is also important to have a decentralized approach with inter-sectoral coordination with different stakeholders such as healthcare workers, community members and the different departments such as the local self-governments, education department, law & order department etc. These lessons learnt from COVID-19 vaccination campaigns must not be forgotten and must be applied in future vaccination campaigns and while framing public health policies.

Comparison of Emulsion and Nanoemulsion Delivery Systems: The Chemical Stability of Curcumin Decreases as Oil Droplet Size Decreases.

The water dispersibility, chemical stability, and bioaccessibility of curcumin, a labile hydrophobic nutraceutical, can be enhanced by incorporating it inside the oil droplets of oil-in-water emulsions or nanoemulsions. In these multiphase systems, the curcumin remains relatively stable to degradation when surrounded by oil but degrades rapidly when surrounded by water. We hypothesized that the size of the lipid droplets would therefore impact the stability of encapsulated curcumin by altering the surface area of oil exposed to water. The effect of droplet surface area on the kinetics of curcumin degradation was therefore studied by producing emulsions with different mean droplet diameters (d32) and therefore different specific surface areas (AS): large (d32 = 20.9 µm; AS = 300 m2 kg-1); medium (d32 = 2.53 µm; AS = 2500 m2 kg-1); small (d32 = 0.26 µm; AS = 24,000 m2 kg-1); and very small (d32 = 0.083 µm; AS = 80,000 m2 kg-1) emulsions. All the emulsions initially had milky-yellow appearances and were relatively stable to aggregation during the course of the experiments. However, rapid creaming was observed in the large and medium emulsions because of their relatively large droplet size. The emulsions all exhibited some color fading during storage, with the rate of curcumin degradation increasing with decreasing droplet size. For instance, the percentage of curcumin remaining in the emulsions after 17 days storage was 91.4 ± 1.5 > 77.3 ± 6.6 > 66.7 ± 1.9 ≫ 30.6 ± 2.8% for the large, medium, small, and very small emulsions, respectively. The more rapid chemical degradation of the curcumin in the smaller droplets can be attributed to the fact that curcumin exchange between the interior and exterior of the droplets occurs more rapidly as the droplet dimensions decrease. Our results indicate that the droplet size plays a critical role in the degradation of curcumin encapsulated in emulsions, which may have important consequences for the formulation of curcumin-enriched foods and beverages with enhanced bioactivity. In particular, it suggests that emulsions are more effective at chemically stabilizing curcumin than nanoemulsions.

Impact of fat crystallization on the resistance of W/O/W emulsions to osmotic stress: Potential for temperature-triggered release.

Water-in-oil-in-water (W/O/W) emulsions can be designed to encapsulate, protect, and release both hydrophilic and hydrophobic functional compounds. In this study, we examined the impact of crystallizing the fat phase on the resistance of W/O/W emulsions to osmotic stress, with the aim of developing osmotic-responsive systems. Polyglycerol polyricinoleate (PGPR) was used as a hydrophobic surfactant to stabilize the inner water droplets, while Quillaja saponin and whey protein isolate (WPI) were used as hydrophilic surfactants to coat the oil droplets. The impact of fat crystallization was examined by using either a liquid (soybean oil, SO) or semi-solid (hydrogenated soybean oil, HSO) fat as the oil phase. An osmotic stress was generated by establishing a sucrose concentration gradient between the internal and external water phases. Alterations in the droplet size, morphology, and stability of the W/O/W emulsions was measured when the sucrose concentration gradient was changed. The W/O droplets in the SO-emulsions swelled/shrank when the external sucrose concentration was below/above the internal sucrose concentration, which is indicative of water diffusing into/out of the droplets. Conversely, there was no change in the size of the W/O droplets in the HSO-emulsions under the same conditions, which was attributed to the mechanical strength of the fat crystal network resisting swelling or shrinking. HSO-emulsions did exhibit swelling when they were heated above a critical temperature, due to melting of the fat crystals and disruption of the crystal network. Our results demonstrate that crystallization of the oil phase of W/O/W emulsions can prevent water transport due to osmotic stress, which may be useful for developing temperature-triggered delivery systems for application in foods, cosmetics, pharmaceuticals, or personal care products.

Enhancement of chemical stability of curcumin-enriched oil-in-water emulsions: Impact of antioxidant type and concentration.

Curcumin is claimed to have many health benefits, but it has low chemical stability. In this study, the influence of food-grade antioxidants on the chemical degradation of curcumin-enriched oil-in-water emulsions was examined. The curcumin degradation rate and extent depended on antioxidant type. The water-soluble antioxidants were more effective at protecting curcumin from degradation than the oil-soluble ones, which may have been because curcumin degrades faster in water than in oil. Interestingly, the amphiphilic antioxidant was almost as effective as the water-soluble ones. The oil-soluble antioxidant actually slightly promoted curcumin degradation. In summary, curcumin retention after storage declined in the following order: 82.6% (Trolox) ~82.2% (ascorbic acid) >79.5% (ascorbyl palmitate) ≫57.9% (control) >52.7% (α-tocopherol). The effectiveness of ascorbic acid in stabilizing curcumin increased as its concentration was raised (0-300 µM). Our results may facilitate the creation of curcumin-enriched foods and beverages with enhanced bioactivity.

Fabrication and characterization of nanostructured lipid carriers (NLC) using a plant-based emulsifier: Quillaja saponin.

Nanostructured lipid carriers (NLCs) are a type of colloidal delivery system that was developed in the pharmaceutical industry to combine the advantages and eliminate the shortcomings of oil-in-water (O/W) nanoemulsions and solid lipid nanoparticles (SLNs). The hydrophobic core of the particles within NLCs consists of a solidified fat phase with a partially disorganized structure, which inhibits morphological changes and bioactive expulsion. In the present study, we formulated NLCs using a hot-homogenization approach using fully hydrogenated soybean oil (HSO) as the lipid phase and quillaja saponins as a natural surfactant. The NLCs formed had a low viscosity and milky white appearance similar to that of O/W nanoemulsions. The fabrication conditions were optimized, including the number of passes through the microfluidizer, stirring conditions, cooling rate, and emulsifier level. Unlike bulk HSO, the emulsified form had to be supercooled substantially to promote crystallization of the lipid droplets, which was attributed to differences in nucleation behavior. The crystallization temperature decreased with increasing saponin concentration, which was probably because smaller droplets were formed at higher emulsifier levels. For instance, at 3, 6, 9, and 12 wt% saponin, the degree of supercooling was 10, 15, 18, and 18 °C, while the mean particle diameter was 0.82, 0.53, 0.41, and 0.44 µm, respectively. The melting and crystallization behavior of the NLCs was characterized using an optical microscope and differential scanning calorimetry (DSC), while the morphology of the NLCs was characterized using transmission electron microscopy (TEM). This analysis showed that the NLCs contained spherical particles with a crystallization temperature around 31 °C. This information may be useful for formulating NLC from natural ingredients for application in the food and beverage industry.

Recent advances in colloidal delivery systems for nutraceuticals: A case study - Delivery by Design of curcumin.

Curcumin is a polyphenolic compound found in turmeric (Curcuma longa) rhizome that has potential biological benefits, including antioxidant, antimicrobial, anti-inflammatory, and anti-cancer activity. Incorporation of curcumin into functional food and beverage products, however, is challenging due to its low water-solubility, poor chemical stability, rapid metabolism, and low oral bioavailability. Researchers are, therefore developing a suite of particle-based delivery systems to maximize the potential health benefits of curcumin. Colloidal delivery systems, such as micelles, microemulsions, nanoemulsions, emulsions, solid lipid nanoparticles, nanostructured lipid carriers, biopolymer nanoparticles, and microgels have all been developed for this purpose. The functional performance of each of these delivery systems depends on its structure and physicochemical properties, such as particle composition, particle size, morphology, physicochemical stability, optical properties, rheology, and sensory attributes. As a result, each delivery system has its advantages and disadvantages for particular applications. Consequently, a delivery system must be specifically designed for the particular bioactive agent to be encapsulated, as well as the particular food matrix it will be incorporated into. In this review, we highlight the potential of the Delivery by Design (DbD) approach for identifying and selecting the most appropriate colloidal delivery system for a particular food application, using curcumin as a model bioactive agent.

Stability of curcumin in oil-in-water emulsions: Impact of emulsifier type and concentration on chemical degradation.

Oral ingestion of curcumin is claimed to be effective against several diseases, including inflammation and cancer. However, its utilization in food, supplement, and pharmaceutical products is often challenging due to its poor water solubility, high chemical instability, and limited oral bioavailability. Emulsion-based delivery systems can be designed to overcome these challenges, but their composition and structure must be optimized to ensure they function appropriately. This study examined the impact of emulsifier type on the formation and stability of curcumin-loaded oil-in-water emulsions: sodium caseinate; Tween 80; quillaja saponin; gum arabic. The effectiveness of these food-grade emulsifiers at forming emulsions by microfluidization was characterized in terms of their surface load, i.e., the mass of emulsifier per unit surface area. The surface loads decreased in the following order: gum arabic (55.3 mg/m2) > > saponins (2.0 mg/m2) > Tween 80 (1.6 mg/m2) > caseinate (1.5 mg/m2), which indicated that much more gum arabic was required to form emulsions than the other emulsifiers. Curcumin-loaded emulsions were then prepared under conditions where there was just enough emulsifier to cover the droplet surfaces ("critical"), and under conditions where there was an excess of emulsifier in the aqueous phase ("excess"). Initially, both critical and excess emulsions were physically stable and had similar appearances. In all emulsions, curcumin degradation during storage occurred more rapidly at pH 7 than at pH 3, and was faster at 55 °C than at 37 °C. The physical and chemical stability of the curcumin-loaded emulsions also depended on emulsifier type. After storage at 55 °C for 15 days, the extent of curcumin degradation decreased in the following order: saponins > > gum arabic ≈ casinate ≈ Tween 80. Moreover, droplet creaming was observed in the critical Tween 80 and saponin emulsions, but not in the other emulsions. These results suggest that saponin accelerated curcumin degradation, possibly due to its ability to promote peroxidation reactions. Emulsifier concentration did not significantly affect curcumin degradation. These results suggest that the physical and chemical stability of curcumin-loaded emulsions is influenced by emulsifier type and level. This information may be useful for formulating emulsion-based delivery systems for curcumin with improved physicochemical and functional properties.

Physical and Chemical Stability of Curcumin in Aqueous Solutions and Emulsions: Impact of pH, Temperature, and Molecular Environment.

The utilization of curcumin as a nutraceutical in food and supplement products is often limited because of its low water solubility, poor chemical stability, and low oral bioavailability. This study examined the impact of pH, storage temperature, and molecular environment on the physical and chemical stability of pure curcumin in aqueous solutions and in oil-in-water emulsions. Unlike naturally occurring curcuminoid mixtures (that contain curcumin, demethoxy-curcumin, and bisdemethoxy-curcumin), pure curcumin was highly unstable to chemical degradation in alkaline aqueous solutions (pH ≥7.0) and tended to crystallize out of aqueous acidic solutions (pH <7). These effects were attributed to changes in the molecular structure of curcumin under different pH conditions. The curcumin crystals formed were relatively large (10-50 µm), which made them prone to rapid sedimentation. The incorporation of curcumin into oil-in-water emulsions (30% MCT, 1 mg curcumin/g MCT, d32 ≈ 298 nm) improved its water dispersibility and chemical stability. After incubation at 37 °C for 1 month, >85% of curcumin was retained by emulsions stored under acidic conditions (pH <7), whereas 62, 60, and 53% was retained by emulsions stored at pH 7.0, 7.4, and 8.0, respectively. There was little change in the color of curcumin-loaded emulsions when stored under acidic conditions, but their yellow color faded when stored under alkaline conditions. There was no evidence of droplet aggregation or creaming in emulsions stored for 31 days at ambient temperature. These results suggest that emulsion-based delivery systems may be suitable for improving the water dispersibility and chemical stability of curcumin, which would facilitate its application in foods and supplements.

Biosynthesis of Anti-Proliferative Gold Nanoparticles Using Endophytic Fusarium oxysporum Strain Isolated from Neem (A. indica) Leaves.

Here we report a simple, rapid, environment friendly approach for the synthesis of gold nanoparticles using neem (Azadirachta indica A. Juss.) fungal endophyte, which based upon morphological and cultural characteristics was eventually identified as Fusarium oxysporum. The aqueous precursor (HAuCl4) solution when reacted with endophytic fungus resulted in the biosynthesis of abundant amounts of well dispersed gold nanoparticles of 10-40 nm with an average size of 22nm. These biosynthesized gold nanoparticles were then characterized by standard analytical techniques such as UV-Visible spectroscopy, X-ray diffraction, Transmission Electron Microscopy and Fourier Transform Infrared Spectroscopy. Cytotoxic activity of these nanoparticles was checked against three different cell types including breast cancer (ZR-75-1), Daudi (Human Burkitt's lymphoma cancer) and normal human peripheral blood mononuclear cells (PBMC), where it was found that our gold nanoparticles are anti-proliferative against cancer cells but completely safe toward normal cells. In addition to this, assessment of toxicity toward human RBC revealed less than 0.1 % hemolysis as compared to Triton X-100 suggesting safe nature of our biosynthesized gold nanoparticles on human cells. Also, our nanoparticles exhibited no anti-fungal (against Aspergillus niger) or anti-bacterial [against Gram positive (Bacillus subtilis & Staphylococcus aureus) and Gram negative (Escherichia coli & Pseudomonas aeruginosa) bacteria] activity thus suggesting their non-toxic, biocompatible nature. The present investigation opens up avenues for ecofriendly, biocompatible nanomaterials to be used in a wide variety of application such as drug delivery, therapeutics, theranostics and so on.

Antioxidant Compounds in Traditional Indian Pickles May Prevent the Process-Induced Formation of Benzene.

Pickles in the Indian market contain ascorbic acid from the raw material used and benzoate as an added preservative that are involved in the formation of benzene in soft drinks. In this work, 24 market pickle samples were surveyed for benzene content, as well as its precursors and other constituents that influence its formation. The analysis showed that pickle samples were high in acid content (low pH) and showed significant amount of ascorbic acid, minerals (Cu and Fe), and benzoic acid present in them. Also, most samples exhibited high antioxidant activity that might be attributed to the ingredients used, such as fruits and spices. The solid-phase microextraction headspace gas chromatography-mass spectrometry method was developed in-house for benzene analysis. Eleven of 24 samples had benzene, with the highest concentration of 4.36 ± 0.82 µg of benzene per kg of pickle for a lime pickle that was also reported to have highest benzoic acid and considerably less hydroxyl radical ((•)OH) scavenging activity. However, benzene levels for all 11 samples were considerably below the World Health Organization regulatory limit of 10 µg/kg for benzene in mineral water. Studies on model systems revealed that the high antioxidant activity of Indian pickles may have had a strong inhibitory effect on benzene formation.

Failure to Use and Sustain Male Condom Usage: Lessons Learned from a Prospective Study among Men Attending STI Clinic in Pune, India.

BACKGROUND: Sustained or consistent use of condoms by men remains a challenge. A study was carried out to identify factors associated with failure to use condoms consistently by men attending STD clinics in Pune, India. METHOD: Among 14137 STI clinic attendees, 8360 HIV sero-negative men were enrolled in a cohort study. The changes in condom usage behavior were studied among 1284 men who returned for first scheduled quarterly follow up, 309 reported consistent condom use at the time of enrollment in the cohort. Data pertaining to heterosexual men practicing high risk behavior were analyzed to identify factors associated with change in condom use behavior using logistic regression model. Demographic, behavioral and biological factors observed to be associated with condom use were fitted in five Cox proportional hazards models to calculate hazard ratios and their 95% confidence intervals to identify independent predictors of failure to sustain condom use behavior. RESULTS: The univariate analysis showed that men who were 30 years or older in age (p = 0.002) and those who did not have contact female sex worker (FSW) were more likely to fail to sustain consistent condom use. However both these factors did not show significant association in multivariable analysis. Marital status and contact with Hijra (eunuch) in lifetime were associated with failure to change in their condom use behavior [AOR 0.33 (CI 0.13-0.82; p = 0.017)]. During the follow up of 2 years, 61 events (15.5 per 100 person years, 95% CI 12.3-19.5 years) of 'failure of condom use' were recorded despite counseling. Older age, contact with non CSW partner and presence of genital ulcer disease / discharge syndrome were significant predictors of failure to sustain condom use. DISCUSSION: Married monogamous older men, who report contact with sex worker and present with genital ulcer disease are at risk of failure to use condom after first exposure to voluntary HIV counseling and testing. This is a scenario of primary prevention program. Condom promotion and counseling needs to be reinforced through follow up counseling among this population.