COVID-19 vaccine uptake and associated factors among adolescents and youths: Findings and implications for future vaccination programmes.

Adolescents and youths are a key part of the population that needs to be protected against the coronavirus disease 2019 (COVID-19). This is because they are more likely to spread the virus to vulnerable individuals. In view of these concerns, this study investigated the uptake of COVID-19 vaccines and associated factors among adolescents and youths attending secondary schools in Zambia. This cross-sectional study was conducted among 1500 school-going adolescents in Lusaka from September 2022 to November 2022. Overall, 1409 participants took part giving a response rate of 94%. Only 29.2% (n = 411) of the participants were vaccinated against COVID-19 at the time of the study. Compared to their unvaccinated counterparts, vaccinated adolescents and youths scored higher for knowledge (66.2% vs 57.8%) and attitudes (76.7% vs 39.4%) regarding COVID-19 vaccines. Healthcare workers, family/friends and social media were key sources of information regarding the vaccine. Factors associated with increased vaccine uptake were positive attitudes (AOR = 33.62, 95% CI: 19.92-56.73), indicating it was stressful to follow COVID-19 preventive measures (AOR = 1.47, 95% CI: 1.09-1.99), participants in Grade 12 (AOR = 3.39, 95% CI: 1.94-5.91), Grade 11 (AOR = 2.59, 95% CI: 1.94-5.91), Grade 10 (AOR = 3.48, 95% CI: 1.98-6.11) and Grade 9 (AOR = 3.04, 95% CI: 1.74-5.32) compared to Grade 8. This study found a relatively low uptake of COVID-19 vaccines among adolescents and youths in Zambia. There is a need to provide adequate strategies to address knowledge and attitude gaps regarding COVID-19 vaccines to improve uptake and reduce future morbidity and mortality.

COVID-19 Vaccine Acceptance and Hesitancy among Healthcare Workers in Lusaka, Zambia; Findings and Implications for the Future.

The uptake of COVID-19 vaccines is critical to address the severe consequences of the disease. Previous studies have suggested that many healthcare workers (HCWs) are hesitant to receive the COVID-19 vaccine, further enhancing hesitancy rates within countries. COVID-19 vaccine acceptance and hesitancy levels are currently unknown among HCWs in Zambia, which is a concern given the burden of infectious diseases in the country. Consequently, this study assessed COVID-19 vaccine acceptance and hesitancy among HCWs in Lusaka, Zambia. A cross-sectional study was conducted among 240 HCWs between August and September 2022, using a semi-structured questionnaire. Multivariable analysis was used to determine the key factors associated with vaccine hesitancy among HCWs. Of the 240 HCWs who participated, 54.2% were females. A total of 72.1% of the HCWs would accept being vaccinated, while 27.9% were hesitant. Moreover, 93.3% of HCWs had positive attitudes towards COVID-19 vaccines, with medical doctors having the highest mean attitude score (82%). Encouragingly, HCWs with positive attitudes towards COVID-19 vaccines had reduced odds of being hesitant (AOR = 0.02, 95% CI: 0.01-0.11, p < 0.001). Overall, acceptance of the COVID-19 vaccine among HCWs in Lusaka, Zambia, was high, especially by those with positive attitudes. However, the current hesitancy among some HCWs is a concern. Consequently, there is a need to address this and encourage HCWs to fully promote vaccination programs going forward.

Antimicrobial Stewardship for Outpatients with Chronic Bone and Joint Infections in the Orthopaedic Clinic of an Academic Tertiary Hospital, South Africa.

Bone and joint infections are associated with prolonged hospitalizations, high morbidity and complexity of care. They are difficult to treat, and successful therapy requires organism-specific antimicrobial therapy at high doses for a prolonged duration as recommended in standard treatment guidelines (STGs). Adherence to the treatment plan is equally important, which is enhanced with knowledge of the condition as well as appropriate antibiotics. Consequently, the aim of this study was to provide antimicrobial stewardship (AMS) services to outpatients with chronic bone and joint infections presenting to the orthopaedic clinic at a public South African tertiary hospital. A total of 44 patients participated in this study. Chronic osteomyelitis was diagnosed in 39 (89%) patients and septic arthritis in 5 (11%). The majority (43%) of infections were caused by Staphylococcus aureus followed by Pseudomonas aeruginosa (14%). Seventy-one antibiotics were prescribed at baseline with rifampicin prescribed the most (39%), followed by ciprofloxacin (23%). The majority (96%) of the antibiotics were not prescribed according to the South African STG; however, interventions were only needed in 31% of prescribed antibiotics (n = 71) since the STG only recommends empiric therapy directed against Staphylococcus aureus. Seventy-seven percent of the patients obtained a high self-reported adherence score at baseline. Consequently, there is a need to improve AMS in bone and joint infections to improve future care.

Current advances in nanodrug delivery systems for malaria prevention and treatment.

Malaria is a life-threatening, blood-borne disease with over two hundred million cases throughout the world and is more prevalent in Sub-Saharan Africa than anywhere else in the world. Over the years, several treatment agents have been developed for malaria; however, most of these active pharmaceutical ingredients exhibit poor aqueous solubility and low bioavailability and may result in drug-resistant parasites, thus increasing malaria cases and eventually, deaths. Factors such as these in therapeutics have led to a better appreciation of nanomaterials. The ability of nanomaterials to function as drug carriers with a high loading capacity and targeted drug delivery, good biocompatibility, and low toxicity renders them an appealing alternative to conventional therapy. Nanomaterials such as dendrimers and liposomes have been demonstrated to be capable of enhancing the efficacy of antimalarial drugs. This review discusses the recent development of nanomaterials and their benefits in drug delivery for the potential treatment of malaria.

Exploring Nanotechnology as a Strategy to Circumvent Antimicrobial Resistance in Bone and Joint Infections.

Bone and joint infections (BJIs) are difficult to treat, necessitating antimicrobial therapy at high doses for an extended period of time, in some cases different from our local guidelines. As a consequence of the rise in antimicrobial-resistant organisms, drugs that were previously reserved for last-line defense are now being used as first line treatment, and the pill burden and adverse effects on patients are leading to nonadherence, encouraging antimicrobial resistance (AMR) to these last-resort medicines. Nanodrug delivery is the field of pharmaceutical sciences and drug delivery which combines nanotechnology with chemotherapy and/or diagnostics to improve treatment and diagnostic outcomes by targeting specific cells or tissues affected. Delivery systems based on lipids, polymers, metals, and sugars have been used in an attempt to provide a way around AMR. This technology has the potential to improve drug delivery by targeting the site of infection and using the appropriate amount of antibiotics to treat BJIs caused by highly resistant organisms. This Review aims to provide an in-depth examination of various nanodrug delivery systems used to target the causative agents in BJI.

A SWOT analysis of nano co-crystals in drug delivery: present outlook and future perspectives.

The formulation of poorly soluble drugs is an intractable challenge in the field of drug design, development and delivery. This is particularly problematic for molecules that exhibit poor solubility in both organic and aqueous media. Usually, this is difficult to resolve using conventional formulation strategies and has resulted in many potential drug candidates not progressing beyond early stage development. Furthermore, some drug candidates are abandoned due to toxicity or have an undesirable biopharmaceutical profile. In many instances drug candidates do not exhibit desirable processing characteristics to be manufactured at scale. Nanocrystals and co-crystals, are progressive approaches in crystal engineering that can solve some of these limitations. While these techniques are relatively facile, they also require optimisation. Combining crystallography with nanoscience can yield nano co-crystals that feature the benefits of both fields, resulting in additive or synergistic effects to drug discovery and development. Nano co-crystals as drug delivery systems can potentially improve drug bioavailability and reduce the side-effects and pill burden of many drug candidates that require chronic dosing as part of treatment regimens. In addition, nano co-crystals are carrier-free colloidal drug delivery systems with particle sizes ranging between 100 and 1000 nm comprising a drug molecule, a co-former and a viable drug delivery strategy for poorly soluble drugs. They are simple to prepare and have broad applicability. In this article, the strengths, weaknesses, opportunities and threats to the use of nano co-crystals are reviewed and a concise incursion into the salient aspects of nano co-crystals is undertaken.

Iridoid Derivatives as Anticancer Agents: An Updated Review from 1970-2022.

The rise of cancer cases has coincided with the urgent need for the development of potent chemical entities and/or modification of existing commodities to improve their efficacy. Increasing evidence suggests that cancer remains one of the leading causes of death globally, with colon cancer cases alone likely to rise exponentially by 2030. The exponential rise in cancer prevalence is largely attributable to the growing change toward a sedentary lifestyle and modern diets, which include genetically modified foods. At present, the prominent treatments for cancer are chemotherapy, surgery, and radiation. Despite slowing cancer progression, these treatments are known to have devastating side effects that may deteriorate the health of the patient, thus, have a low risk-benefit ratio. In addition, many cancer drugs have low bioavailability, thereby limiting their therapeutic effects in cancer patients. Moreover, the drastic rise in the resistance of neoplastic cells to chemotherapeutic agents is rendering the use of some drugs ineffective, thereby signaling the need for more anticancer chemical entities. As a result, the use of natural derivatives as anticancer agents is gaining considerable attention. Iridoids have the potential to form conjugates with other anticancer, antidiabetic, antileishmanial, and antimalarial drugs, which synergistically have the potential to increase their effects. Published studies have identified the role of iridoids, which, if fully explored, may result in cheaper and less toxic alternative/adjuvant cancer drugs. The subject of this article is natural and synthetic iridoid derivatives and their potential therapeutic roles as anticancer agents.

Knowledge, Attitudes, and Acceptance of COVID-19 Vaccines among Secondary School Pupils in Zambia: Implications for Future Educational and Sensitisation Programmes.

The coronavirus disease 2019 (COVID-19) pandemic resulted in the closure of schools to slow the spread of the virus across populations, and the administration of vaccines to protect people from severe disease, including school children and adolescents. In Zambia, there is currently little information on the acceptance of COVID-19 vaccines among school-going children and adolescents despite their inclusion in the vaccination programme. This study assessed the knowledge, attitudes, and acceptance of COVID-19 vaccines among secondary school pupils in Lusaka, Zambia. A cross-sectional study was conducted from August 2022 to October 2022. Of the 998 participants, 646 (64.7%) were female, and 127 (12.7%) would accept to be vaccinated. Those who were willing to be vaccinated had better knowledge (68.5% vs. 56.3%) and a positive attitude (79.1% vs. 33.7%) compared to those who were hesitant. Overall, the odds of vaccine acceptance were higher among pupils who had higher knowledge scores (AOR = 11.75, 95% CI: 6.51-21.2), positive attitude scores (AOR = 9.85, 95% CI: 4.35-22.2), and those who knew a friend or relative who had died from COVID-19 (AOR = 3.27, 95% CI: 2.14-5.09). The low vaccine acceptance among pupils is of public health concern, emphasising the need for heightened sensitisation programmes that promote vaccine acceptance among pupils in Zambia.

Challenges faced by blind patients using chronic medication at a tertiary hospital in South Africa.

Background: Difficulties faced by blind patients in using medicines are largely unknown and underexplored. This limits the ability of health providers and health policy makers to plan and provide for medicine related needs of this special group. Objectives: To describe the challenges faced by blind patients around Mankweng Hospital when taking chronic medications and to identify methods used to overcome the challenges. Methods: Quantitative cross-sectional descriptive study, where questionnaires were administered to 82 blind patients, 18 years and older, and who were on chronic medications. Data was analysed using the Statistical Package for the Social Sciences (SPSS) software. Results: Majority of participants were elderly (59%) and had partial blindness (78%). Challenges faced by participants included inability to locate and identify medication (60%), missing doses (64%), inaccurate dosing and spilling medicines (33%). A staggering 68.3% of the participants did not have specific methods to overcome challenges. Conclusions: Challenges faced by the blind and visually impaired are similar across the world. However, participants are unaware of other simple, feasible methods available in the market. Current methods used by the participants to overcome the challenges encountered are minimal or caregiver dependent. Programs may be set up at clinics, hospitals and health care centers to teach the visually impaired simple and inexpensive methods to help administer medications. Contribution: Results obtained may be used to raise awareness in health care policy makers of the under-explored challenges faced by the partially blind or completely blind patients in the use of medicines.

The Use of Medicinal Plant-Derived Metallic Nanoparticles in Theranostics.

In the quest to effectively diagnose and treat the diseases that afflict mankind, the development of a tool capable of simultaneous detection and treatment would provide a significant cornerstone for the survival and control of these diseases. Theranostics denotes a portmanteau of therapeutics and diagnostics which simultaneously detect and treat ailments. Research advances have initiated the advent of theranostics in modern medicine. Overall, theranostics are drug delivery systems with molecular or targeted imaging agents integrated into their structure. The application of theranostics is rising exponentially due to the urgent need for treatments that can be utilized for diagnostic imaging as an aid in precision and personalised medicine. Subsequently, the emergence of nanobiotechnology and the green synthesis of metallic nanoparticles (MNPs) has provided one such avenue for nanoscale development and research. Of interest is the drastic rise in the use of medicinal plants in the synthesis of MNPs which have been reported to be potentially effective in the diagnosis and treatment of diseases. At present, medicinal plant-derived MNPs have been cited to have broad pharmacological applications and have been studied for their potential use in the treatment and management of cancer, malaria, microbial and cardiovascular diseases. The subject of this article regards the role of medicinal plants in the synthesis of MNPs and the potential role of MNPs in the field of theranostics.

Current Advances in Specialised Niosomal Drug Delivery: Manufacture, Characterization and Drug Delivery Applications.

Development of nanomaterials for drug delivery has received considerable attention due to their potential for achieving on-target delivery to the diseased area while the surrounding healthy tissue is spared. Safe and efficiently delivered payloads have always been a challenge in pharmaceutics. Niosomes are self-assembled vesicular nanocarriers formed by hydration of a non-ionic surfactant, cholesterol or other molecules that combine to form a versatile drug delivery system with a variety of applications ranging from topical delivery to targeted delivery. Niosomes have advantages similar to those of liposomes with regards to their ability to incorporate both hydrophilic and hydrophobic payloads. Moreover, niosomes have simple manufacturing methods, low production cost and exhibit extended stability, consequently overcoming the major drawbacks associated with liposomes. This review provides a comprehensive summary of niosomal research to date, including the types of niosomes and critical material attributes (CMA) and critical process parameters (CPP) of niosomes and their effects on the critical quality attributes (CQA) of the technology. Furthermore, physical characterisation techniques of niosomes are provided. The review then highlights recent applications of specialised niosomes in drug delivery. Finally, limitations and prospects for this technology are discussed.

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders.

Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.

Chemical Characterization and Nutritional Markers of South African Moringa oleifera Seed Oils.

Moringa oleifera Lam (syn. M. ptreygosperma Gaertn.) leaves are globally acclaimed for their nutritional content and mitigation of malnutrition. In most impoverished rural communities including Limpopo, Mpumalanga and KwaZulu Natal of South Africa, powdered leaves of Moringa oleifera are applied as a nutritional supplement for readily available food such as porridge for malnourished children and even breast-feeding mothers. Widely practiced and admired is also the use of the plant seed in the do-it-yourself purification of water by rural South Africans. This study aimed at identifying the chemical and nutritional marker compounds present in South African Moringa oleifera seed oils using high resolution 1-2-dimension gas chromatography in order to give scientific validation to its uses in cosmetics and particularly in culinary practices. Results obtained from two-dimension tandem mass spectrometry chemical signature revealed over 250 compounds, five times more than those reported from one-dimension gas chromatography. Whereas previous reports from gas chromatography-mass spectrometry analysis reported oleic acid (70-78%) as the major compound from oil samples from other countries, M. oleifera seed oil from South Africa is marked by cis-13-octadeaconic acid with 78.62% and 41.9% as the predominant monounsaturated fatty acid in the hexane and dichloromethane extracts respectively. This was followed by cis-vaccenic acid, an isomer of oleic acid at 51% in the acetone extract, 9-octadecanoic acid-(z)-methyl ester at 39.18%, 21.34% and 10.06% in dichloromethane, hexane and acetone extracts respectively. However, a principal component analysis with R2 = 0.98 of the two-dimension tandem mass spectrometry cum chemometric analysis indicated n-hexadecanoic acid, oleic acid, 9-octadecanoic acid-(z)-methyl ester and cis-vaccenic acid with a probability of 0.96, 0.88, 0.80 and 0.79 respectively as the marker compounds that should be used for the quality control of moringa seed oils from South Africa. This study demonstrates that South African Moringa oleifera oils contain C-18 monounsaturated fatty acids similar to oils from Egypt (76.2%), Thailand (71.6%) and Pakistan (78.5%) just to mention but a few. These fatty acids are sunflower and olive oil type-compounds and therefore place moringa seed oil for consideration as a cooking oil amongst its other uses.

Current Advances in Nano-Based and Polymeric Stimuli-Responsive Drug Delivery Targeting the Ocular Microenvironment: A Review and Envisaged Future Perspectives.

Optimal vision remains one of the most essential elements of the sensory system continuously threatened by many ocular pathologies. Various pharmacological agents possess the potential to effectively treat these ophthalmic conditions; however, the use and efficacy of conventional ophthalmic formulations is hindered by ocular anatomical barriers. Recent novel designs of ophthalmic drug delivery systems (DDS) using nanotechnology show promising prospects, and ophthalmic formulations based on nanotechnology are currently being investigated due to their potential to bypass these barriers to ensure successful ocular drug delivery. More recently, stimuli-responsive nano drug carriers have gained more attention based on their great potential to effectively treat and alleviate many ocular diseases. The attraction is based on their biocompatibility and biodegradability, unique secondary conformations, varying functionalities, and, especially, the stimuli-enhanced therapeutic efficacy and reduced side effects. This review introduces the design and fabrication of stimuli-responsive nano drug carriers, including those that are responsive to endogenous stimuli, viz., pH, reduction, reactive oxygen species, adenosine triphosphate, and enzymes or exogenous stimuli such as light, magnetic field or temperature, which are biologically related or applicable in clinical settings. Furthermore, the paper discusses the applications and prospects of these stimuli-responsive nano drug carriers that are capable of overcoming the biological barriers of ocular disease alleviation and/or treatment for in vivo administration. There remains a great need to accelerate the development of stimuli-responsive nano drug carriers for clinical transition and applications in the treatment of ocular diseases and possible extrapolation to other topical applications such as ungual or otic drug delivery.

Applications of Electrospun Drug-Eluting Nanofibers in Wound Healing: Current and Future Perspectives.

Wounds are a consequence of disruption in the structure, integrity, or function of the skin or tissue. Once a wound is formed following mechanical or chemical damage, the process of wound healing is initiated, which involves a series of chemical signaling and cellular mechanisms that lead to regeneration and/or repair. Disruption in the healing process may result in complications; therefore, interventions to accelerate wound healing are essential. In addition to mechanical support provided by sutures and traditional wound dressings, therapeutic agents play a major role in accelerating wound healing. The medicines known to improve the rate and extent of wound healing include antibacterial, anti-inflammatory, and proliferation enhancing agents. Nonetheless, the development of these agents into eluting nanofibers presents the possibility of fabricating wound dressings and sutures that provide mechanical support with the added advantage of local delivery of therapeutic agents to the site of injury. Herein, the process of wound healing, complications of wound healing, and current practices in wound healing acceleration are highlighted. Furthermore, the potential role of drug-eluting nanofibers in wound management is discussed, and lastly, the economic implications of wounds as well as future perspectives in applying fiber electrospinning in the design of wound dressings and sutures are considered and reported.

Assessment of the availability of snakebite antivenom in health facilities in Ndola District, Zambia: a cross-sectional study.

BACKGROUND: Despite snakebite antivenom being included on the WHO list of essential medicines, many parts of the world, especially Africa, lack effective and safe antivenoms. METHODS: A descriptive, field-based, cross-sectional study was undertaken from August to November 2020 in 40 out of 71 health facilities in Ndola district. Interviews and physical inspection were conducted at each facility. RESULTS: The study revealed that only three (8%) of all the private health facilities had antivenom available at the time of the assessment. Factors significantly associated with antivenom supply included lack of central country supply (90%), lack of demand of the antivenom (55%) and no budget allocation for the antivenom (95%). CONCLUSIONS: Despite the high number of notified snakebites within Ndola district, there remains poor availability of snakebite antivenom within the district.

Application of Lipid-Based Nanocarriers for Antitubercular Drug Delivery: A Review.

The antimicrobial drugs currently used for the management of tuberculosis (TB) exhibit poor bioavailability that necessitates prolonged treatment regimens and high dosing frequency to achieve optimal therapeutic outcomes. In addition, these agents cause severe adverse effects, as well as having detrimental interactions with other drugs used in the treatment of comorbid conditions such as HIV/AIDS. The challenges associated with the current TB regimens contribute to low levels of patient adherence and, consequently, the development of multidrug-resistant TB strains. This has led to the urgent need to develop newer drug delivery systems to improve the treatment of TB. Targeted drug delivery systems provide higher drug concentrations at the infection site, thus leading to reduced incidences of adverse effects. Lipid-based nanocarriers have proven to be effective in improving the solubility and bioavailability of antimicrobials whilst decreasing the incidence of adverse effects through targeted delivery. The potential application of lipid-based carriers such as liposomes, niosomes, solid lipid nanoparticles, nanostructured lipid carriers, nano and microemulsions, and self-emulsifying drug delivery systems for the treatment of TB is reviewed herein. The composition of the investigated lipid-based carriers, their characteristics, and their influence on bioavailability, toxicity, and sustained drug delivery are also discussed. Overall, lipid-based systems have shown great promise in anti-TB drug delivery applications. The summary of the reviewed data encourages future efforts to boost the translational development of lipid-based nanocarriers to improve TB therapy.

Vesicular drug delivery for the treatment of topical disorders: current and future perspectives.

OBJECTIVES: Vesicular drug delivery has become a useful approach for therapeutic administration of pharmaceutical compounds. Lipid vesicles have found application in membrane biology, immunology, genetic engineering and theragnostics. This review summarizes topical delivery, specifically dermal/transdermal, ocular and transungual, via these vesicles, including future formulation perspectives. KEY FINDINGS: Liposomes and their subsequent derivatives, viz. niosomes, transferosomes, pharmacososmes and ethosomes, form a significant part of vesicular systems that have been successfully utilized in treating an array of topical disorders. These vesicles are thought to be a safe and effective mode of improving the delivery of lipophilic and hydrophilic drugs. SUMMARY: Several drug molecules are available for topical disorders. However, physicochemical properties and undesirable toxicity have limited their efficacy. Vesicular delivery systems have the potential to overcome these shortcomings due to properties such as high biocompatibility, simplicity of surface modification and suitability as controlled delivery vehicles. However, incorporating these systems into environmentally responsive dispersants such as hydrogels, ionic liquids and deep eutectic solvents may further enhance therapeutic prowess of these delivery systems. Consequently, improved vesicular drug delivery can be achieved by considering combining some of these formulation approaches.

Nano Co-Crystal Embedded Stimuli-Responsive Hydrogels: A Potential Approach to Treat HIV/AIDS.

Currently, the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS) can only be treated successfully, using combination antiretroviral (ARV) therapy. Lamivudine (3TC) and zidovudine (AZT), two compounds used for the treatment of HIV and prevention of disease progression to AIDS are used in such combinations. Successful therapy with 3TC and AZT requires frequent dosing that may lead to reduced adherence, resistance and consequently treatment failure. Improved toxicity profiles of 3TC and AZT were observed when combined as a nano co-crystal (NCC). The use of stimuli-responsive delivery systems provides an opportunity to overcome the challenge of frequent dosing, by controlling and/or sustaining delivery of drugs. Preliminary studies undertaken to identify a suitable composition for a stimulus-responsive in situ forming hydrogel carrier for 3TC-AZT NCC were conducted, and the gelation and erosion time were determined. A 25% w/w Pluronic® F-127 thermoresponsive hydrogel was identified as a suitable carrier as it exhibited a gelation time of 5 min and an erosion time of 7 days. NCC-loaded hydrogels were evaluated using in vitro dissolution and cytotoxicity assays. In vitro dissolution undertaken using membrane-less diffusion over 168 h revealed that 3TC and AZT release from NCC-loaded hydrogels was complete and followed zero-order kinetic processes, whereas those loaded with the micro co-crystal and physical mixture were incomplete and best described using the Korsmeyer-Peppas kinetic model. The release of AZT and 3TC from the physical mixture and MCC-loaded gel exhibited a value for n of 0.595 for AZT release from the physical mixture and 0.540 for the MCC technology, whereas the release exponent for 3TC was 0.513 for the physical mixture and 0.557 for the MCC technology indicating that diffusion and erosion controlled 3TC and AZT release. In vitro cytotoxicity assay data revealed that the addition of NCC to the thermoresponsive hydrogel resulted in an improved cell viability of 88.0% ± 5.0% when compared to the cell viability of the NCC of 76.9% ± 5.0%. The results suggest that the use of a thermoresponsive nanosuspension may have the potential to be delivered as an intramuscular injection that can subsequently increase bioavailability and permit dose reduction and/or permit use of a longer dosing frequency.

Nano-Biomimetic Drug Delivery Vehicles: Potential Approaches for COVID-19 Treatment.

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a "Trojan horse" for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.