A commonly held view is that nanocarriers conjugated to polyethylene glycol (PEG) are nonimmunogenic. However, many studies have reported that unexpected immune responses have occurred against PEG-conjugated nanocarriers. One unanticipated response is the rapid clearance of PEGylated nanocarriers upon repeat administration, called the accelerated blood clearance (ABC) phenomenon. ABC involves the production of antibodies toward nanocarrier components, including PEG, which reduces the safety and effectiveness of encapsulated therapeutic agents. Another immune response is the hypersensitivity or infusion reaction referred to as complement (C) activation-related pseudoallergy (CARPA). Such immunogenicity and adverse reactivities of PEGylated nanocarriers may be of potential concern for the clinical use of PEGylated therapeutics. Accordingly, screening of the immunogenicity and CARPA reactogenicity of nanocarrier-based therapeutics should be a prerequisite before they can proceed into clinical studies. This review presents PEGylated liposomes, immunogenicity of PEG, the ABC phenomenon, C activation and lipid-induced CARPA from a toxicological point of view, and also addresses the factors that influence these adverse interactions with the immune system.

No abstract

Most countries are currently gravitating towards vaccination as mainstay strategy to quell COVID-19 transmission. Between December 2020 and January 2021, we conducted a follow-up online survey in Somalia to monitor adherence to COVID-19 preventive measures, and COVID-19 vaccine acceptability and reasons for vaccine hesitancy. Adherence was measured via a composite adherence score based on four measures (physical distancing, face mask use, hand hygiene, and mouth covering when coughing/sneezing). We analyzed 4543 responses (mean age: 23.5 ± 6.4 years, 62.4% males). The mean adherence score during this survey was lower than the score during a similar survey in April 2020. A total of 76.8% of respondents were willing to receive the COVID-19 vaccine. Flu-like symptoms were more frequently reported in the current survey compared to previous surveys. Multiple logistic regression showed that participants who experienced flu-like symptoms, those in the healthcare sector, and those with higher adherence scores had higher odds for vaccine acceptability while being a female reduced the willingness to be vaccinated. In conclusion, our data suggest that the decreasing adherence to COVID-19 preventive measures may have caused increased flu-like symptoms over time. COVID-19 vaccine acceptance in Somalia is relatively high but could be improved by addressing factors that contribute to vaccine hesitancy.

, Poloxamer-based thermoresponsive ketorolac tromethamine in situ gel preparations: Design, characterisation, toxicity and transcorneal permeation studies, European Journal of Pharmaceutics and Biopharmaceutics (2017), doi: http://dx.doi.org/10. 1016/j.ejpb.2017.01.008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThis study was aimed at preparing, characterising and evaluating in situ gel formulations based on a blend of two hydrophilic polymers i.e. poloxamer 407 (P407) and poloxamer 188 (P188) for a sustained ocular delivery of ketorolac tromethamine (KT). Drug-polymer interaction studies were performed using DSC and FT-IR. The gelation temperature (T sol-gel ), gelation time, rheological behaviour, mucoadhesive characteristics of these gels, transcorneal permeation and ocular irritation as well as toxicity was investigated. DSC and FT-IR studies revealed that there may be electrostatic interactions between the drug and the polymers used.P188 modified the T sol/gel of P407 bringing it close to eye temperature (35 o C) compared with the formulation containing P407 alone. Moreover, gels that comprised P407 and P188 exhibited a pseudoplastic behaviour at different concentrations. Furthermore, mucoadhesion study using mucin discs showed that in situ gel formulations have good mucoadhesive characteristics upon increasing the concentration of P407. When comparing formulations PP11 and PP12, the work of adhesion decreased significantly (P < 0.001) from 377.9 ± 7.79 mN.mm to 272.3 ± 6.11 mN.mm. In vitro release and ex vivo permeation experiments indicated that the in situ gels were able to prolong and control KT release as only 48% of the KT released within 12 h. In addition, the HET-CAM and BCOP tests confirmed the nonirritancy of KT loaded in situ gels, and HET-CAM test demonstrated the ability of ocular protection against strongly irritant substances. MTT assay on primary corneal epithelial cells revealed that in situ gel formulations loaded with KT showed reasonable and acceptable percent cell viability compared with control samples.

No abstract

The present work aimed to prolong the contact time of flurbiprofen (FBP) in the ocular tissue to improve the drug anti-inflammatory activity. Different niosome systems were fabricated adopting thin-film hydration technique and using the nonionic surfactant Span 60. The morphology of the prepared niosomes was characterized by scanning electron microscopy (SEM). Physical characterization by differential scanning calorimetry, X-ray powder diffraction and Fourier transform infrared spectroscopy were conducted for the optimized formula (F5) that was selected on the basis of percent entrapment efficiency, vesicular size and total lipid content. F5 was formulated as 1% w/w Carpobol 934 gel. Pharmacokinetic parameters of FBP were investigated following ocular administration of F5-loaded gel system, F5 niosome dispersion or the corresponding FBP ocular drops to albino rabbits dispersion. Anti-inflamatory effect of F5-loaded carbopol gel was investigated by histopathological examination of the corneal tissue before and after the treatment of inflamed rabbit eye with the system. Results showed that cholesterol content, surfactant type. and total lipid contents had an apparent impact on the vesicle size of the formulated niosomes. Physical characterization revealed reduced drug crystallinity and incidence of interaction with other niosome contents. F5-loaded gel showed higher C, area under the curve (AUC), and thus higher ocular bioavailability than those of the corresponding FBP ocular solution. F5-loaded gel showed a promising rapid anti-inflammatory effect in the inflamed rabbit eye. These findings will eradicate the necessity for frequent ocular drug instillation and thus, improve patient compliance.

The aim of this work was to formulate chitosan (CS) based nanoparticles (NPs) loaded with ketorolac tromethamine (KT) intended for topical ocular delivery. NPs were prepared using ionic gelation method incorporating tri-polyphosphate (TPP) as cross-linker. Following the preparation, the composition of the system was optimised in terms of their particle size, zeta potential, entrapment efficiency (EE) and morphology, as well as performing structural characterisation studies using FT-IR and DSC. The data suggested that the size of the NPs was affected by CS/TPP ratio where the diameter of the NPs ranged from 108.0 ± 2.4 nm to 257.2 ± 18.6 nm. A correlation between drug EE and the corresponding drug concentration added to the formulation was observed, where the EE of the NPs increased with increasing drug concentration, for up to 10 mg/mL. FT-IR and DSC revealed that KT was dispersed within the NPs where the phosphate groups of TPP were associated with the ammonium groups of CS. The in vitro release profile of KT from CS NPs showed significant differences (P<0.05) compared to KT solution. Furthermore, mucoadhesion studies revealed adhesive properties of the formulated NPs. The KT loaded NPs were found to be stable when stored at different storage conditions for a period of 3 months. The ex vivo corneal permeation studies performed on excised porcine eye balls confirmed the ability of NPs in retaining the drug on the eye surface for a relatively longer time. These results demonstrate the potential of CS based NPs for the ocular delivery of KT.

Background Healthcare workers (HCWs) fighting against the COVID-19 pandemic are under incredible pressure, which puts them at risk of developing mental health problems. This study aimed to determine the prevalence of depression, anxiety, and stress among HCWs responding to COVID-19 and its associated factors. Methods A multi-country cross-sectional study was conducted during July–August 2020 among HCWs responding to COVID-19 in nine Eastern Mediterranean Region (EMR) countries. Data were collected using an online questionnaire administered using KoBo Toolbox. Mental problems were assessed using the Depression, Anxiety, and Stress Scale (DASS-21). Results A total of 1448 HCWs from nine EMR countries participated in this study. About 51.2% were male and 52.7% aged ≤ 30 years. Of all HCWs, 57.5% had depression, 42.0% had stress, and 59.1% had anxiety. Considering the severity, 19.2%, 16.1%, 26.6% of patients had severe to extremely severe depression, stress, and anxiety, respectively. Depression, stress, anxiety, and distress scores were significantly associated with participants’ residency, having children, preexisting psychiatric illness, and being isolated for COVID-19. Furthermore, females, those working in a teaching hospital, and specialists had significantly higher depression and stress scores. Married status, current smoking, diabetes mellitus, having a friend who died with COVID-19, and high COVID-19 worry scores were significantly associated with higher distress scores. Conclusions Mental problems were prevalent among HCWs responding to COVID-19 in EMR. Therefore, special interventions to promote mental well-being among HCWs responding to COVID-19 need to be immediately implemented.