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.

The use of quantitative analysis and Hansen solubility parameter predictions for the selection of excipients for lipid nanocarriers to be loaded with water soluble and insoluble compounds.

The aim of these studies was to determine the miscibility of different API with lipid excipients to predict drug loading and encapsulation properties for the production of solid lipid nanoparticles and nanostructured lipid carriers. Five API exhibiting different physicochemical characteristics, viz., clarithromycin, efavirenz, minocycline hydrochloride, mometasone furoate, and didanosine were used and six solid lipids in addition to four liquid lipids were investigated. Determination of solid and liquid lipids with the best solubilization potential for each API were performed using a traditional shake-flask method and/or a modification thereof. Hansen solubility parameters of the API and different solid and liquid lipids were estimated from their chemical structure using Hiroshi Yamamoto's molecular breaking method of Hansen Solubility Parameters in Practice software. Experimental results were in close agreement with solubility parameter predictions for systems with ΔδT < 4.0 MPa1/2. A combination of Hansen solubility parameters with experimental drug-lipid miscibility tests can be successfully applied to predict lipids with the best solubilizing potential for different API prior to manufacture of solid lipid nanoparticles and nanostructured lipid carriers.

Chitosan-Coated SLN: A Potential System for Ocular Delivery of Metronidazole.

Ophthalmic drops for ocular delivery exhibit inadequate residence time, which often requires multiple daily dosing that may result in patient non-adherence. In this study, the development of a once-daily-dosed chitosan-coated metronidazole (MTZ)-loaded solid lipid nanoparticles (SLNs) for ocular delivery was undertaken. Melt emulsification and ultrasonication were used to manufacture MTZ-loaded SLN, which were subsequently coated with chitosan (CS) by mechanical stirring using a 0.1% w/v solution. Gelucire® 48/16 and Transcutol® HP were used as the solid lipid and synthetic solvent, respectively, with Tween® 20 included as a stabilizing agent. The critical quality attributes (CQA) of the optimized CS-coated SLN that was monitored included particle size, polydispersity index, Zeta potential, % entrapment efficiency, % MTZ loading, pH, and osmolarity. The optimized coated nanocarriers were evaluated using laser Doppler anemometry (LDA) and were determined to be stable, with particle sizes in the nanometre range. In vitro mucoadhesion, MTZ release and short-term stability, in addition to the determination of the shape of the optimized CS-coated SLN, were undertaken. The mucoadhesive properties of the optimized CS-coated MTZ-loaded SLN demonstrated increased ocular availability, which may allow dose reduction or longer intervals between doses by improving precorneal retention and ocular availability. Overall, our findings suggest that CS-coated MTZ-loaded SLNs have the potential for clinical application, to enhance ocular delivery through the release of MTZ.

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.

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.

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.

Biocompatibility of Biomaterials for Nanoencapsulation: Current Approaches.

Nanoencapsulation is an approach to circumvent shortcomings such as reduced bioavailability, undesirable side effects, frequent dosing and unpleasant organoleptic properties of conventional drug delivery systems. The process of nanoencapsulation involves the use of biomaterials such as surfactants and/or polymers, often in combination with charge inducers and/or ligands for targeting. The biomaterials selected for nanoencapsulation processes must be as biocompatible as possible. The type(s) of biomaterials used for different nanoencapsulation approaches are highlighted and their use and applicability with regard to haemo- and, histocompatibility, cytotoxicity, genotoxicity and carcinogenesis are discussed.

Short Term Stability Testing of Efavirenz-Loaded Solid Lipid Nanoparticle (SLN) and Nanostructured Lipid Carrier (NLC) Dispersions.

The short term stability of efavirenz-loaded solid lipid nanoparticle and nanostructured lipid carrier dispersions was investigated. Hot High Pressure Homogenization with the capability for scale up production was successfully used to manufacture the nanocarriers without the use of toxic organic solvents for the first time. Glyceryl monostearate and Transcutol® HP were used as the solid and liquid lipids. Tween® 80 was used to stabilize the lipid nanocarriers. A Box-Behnken Design was used to identify the optimum operating and production conditions viz., 1100 bar for 3 cycles for the solid lipid nanoparticles and 1500 bar for 5 cycles for nanostructured lipid carriers. The optimized nanocarriers were predicted to exhibit 10% efavirenz loading with 3% and 4% Tween® 80 for solid lipid nanoparticles and nanostructured lipid carriers, respectively. Characterization of the optimized solid lipid nanoparticle and nanostructured lipid carrier formulations in relation to shape, surface morphology, polymorphism, crystallinity and compatibility revealed stable formulations with particle sizes in the nanometer range had been produced. The nanocarriers had excellent efavirenz loading with the encapsulation efficiency >90%. The optimized nanocarriers exhibited biphasic in vitro release patterns with an initial burst release during the initial 0-3 h followed by sustained release over a 24 h period The colloidal systems showed excellent stability in terms of Zeta potential, particle size, polydispersity index and encapsulation efficiency when stored for 8 weeks at 25 °C/60% RH in comparison to when stored at 40 °C/75% RH. The formulations manufactured using the optimized conditions and composition proved to be physically stable as aqueous dispersions.