Despite the substantial body of research investigating the use of liposomes, niosomes and other bilayer vesicles for drug delivery, the translation of these systems into licensed products remains limited. Indeed, recent shortages in the supply of liposomal products demonstrate the need for new scalable production methods for liposomes. Therefore, the aim of our research has been to consider the application of microfluidics in the manufacture of liposomes containing either or both a water soluble and a lipid soluble drug to promote co-delivery of drugs. For the first time, we demonstrate the entrapment of a hydrophilic and a lipophilic drug (metformin and glipizide respectively) both individually, and in combination, using a scalable microfluidics manufacturing system. In terms of the operating parameters, the choice of solvents, lipid concentration and aqueous:solvent ratio all impact on liposome size with vesicle diameter ranging from ∼90 to 300nm. In terms of drug loading, microfluidics production promoted high loading within ∼100nm vesicles for both the water soluble drug (20-25% of initial amount added) and the bilayer embedded drug (40-42% of initial amount added) with co-loading of the drugs making no impact on entrapment efficacy. However, co-loading of glipizide and metformin within the same liposome formulation did impact on the drug release profiles; in both instances the presence of both drugs in the one formulation promoted faster (up to 2 fold) release compared to liposomes containing a single drug alone. Overall, these results demonstrate the application of microfluidics to prepare liposomal systems incorporating either or both an aqueous soluble drug and a bilayer loaded drug.
Exosomes are small extracellular vesicles that have emerged as an important tool for intercellular communication. In the central nervous system, exosomes can mediate glia and neuronal communication. Once released from the donor cell, exosomes can act as discrete vesicles and travel to distant and proximal recipient cells to alter cellular function. Microglia cells secrete exosomes due to stress stimuli of alcohol abuse. The goal of this study was to investigate the effects of alcohol exposure on the biogenesis and composition of exosomes derived from microglia cell line BV-2. The BV-2 cells were cultured in exosome-free media and were either mock treated (control) or treated with 50 mM or 100 mM of alcohol for 48 and 72 h. Our results demonstrated that alcohol significantly impacted BV-2 cell morphology, viability, and protein content. Most importantly, our studies revealed that exosome biogenesis and composition was affected by alcohol treatment.
Objective To investigate the toxicity and antibacterial application of antimicrobial peptide-functionalized silver-coated carbon nanotubes against Staphylococcus infection using a full thickness human three-dimensional skin model. Materials and methods The three-dimensional skin formation on the scaffolds was characterized by electron microscopy and investigation of several skin cell markers by real time–reverse transcriptase polymerase chain reaction. Functionalized silver-coated carbon nanotubes were prepared using carboxylated silver-coated carbon nanotubes with antimicrobial peptides such as TP359, TP226 and TP557. Following the characterization and toxicity evaluation, the antibacterial activity of functionalized silver-coated carbon nanotubes against Staphylococcus aureus was investigated using a bacterial enumeration assay and scanning electron microscopy. For this purpose, a scar on the human three-dimensional skin grown on Alvetex scaffold using keratinocytes and fibroblasts cells was created by taking precaution not to break the scaffold beneath, followed by incubation with 5 µg/mL of functionalized silver-coated carbon nanotubes re-suspended in minimum essential medium for 2 h. Post 2-h incubation, 200 µL of minimum essential medium containing 1 × 104 colony forming units of Staphylococcus aureus were incubated for 2 h. After incubation with bacteria, the colony forming unit/gram (cfu/g) of skin tissue were counted using the plate count assay and the samples were processed for scanning electron microscopy analysis. Results MTT assay revealed no toxicity of functionalized silver-coated carbon nanotubes to the skin cells such as keratinocytes and fibroblasts at 5 µg/mL with 98% cell viability. The bacterial count increased from 104 to 108 cfu/g in the non-treated skin model, whereas skin treated with functionalized silver-coated carbon nanotubes showed only a small increase from 104 to 105 cfu/g (1000-fold viable cfu difference). Scanning electron microscopy analysis showed the presence of Staphylococcus aureus on the non-treated skin as opposed to the treated skin. Conclusion Thus, our results showed that functionalized silver-coated carbon nanotubes are not only non-toxic, but also help reduce the infection due to their antibacterial activity. These findings will aid in the development of novel antibacterial skin substitutes.
Microfluidics is a very facile and fast method of particulate production. Besides, it enables the manufacturing of size tuned particulate systems. Niosomes due to structural similarities have importance as alternative drug delivery systems to liposomes. Niosomes can be encapsulated or co-encapsulated with hydrophilic and lipophilic drugs. The research presented here includes the optimization of method parameters for niosome production as well as evaluation of the efficiency of microfluidics to encapsulate and co-encapsulate the drugs. For this purpose, metformin (MET) and garcinol (GC) were the model drugs. Two different non-ionic surfactants (NIS), namely Tween-20 and Span-60 with significant difference in hydrophilic-lipophilic balance (HLB) value, were chosen to analyze their efficiency to form niosomes and encapsulate one or more drugs.
Introduction: Human respiratory syncytial virus (RSV) is a common respiratory virus that causes severe lower respiratory tract infection in infants, children and aged adults. Currently, there is no active prophylaxis present in the market for RSV infection; however, there are over a dozen compounds being tested in the laboratory as well as clinical trials. To increase the efficiency and safety of these therapeutics, there is a need for delivery vehicles. Areas covered: Liposomes can be used for delivering anti-RSV agents with the advantage of modulating and eliciting the desired adjuvant effect by the different combination of lipids. This review discusses the promising application of liposome for anti-RSV therapeutics. Expert opinion: Liposomes are attracting attention for delivery of pulmonary therapeutics, since they offer compatibility for delivering drugs, vaccines and other therapeutic molecules. Variation in liposome size and composition gives flexibility for the amount and number of deliverables, whilst targeted delivery with the capability for immunomodulation makes liposomes a promising candidate for RSV therapeutic applications.
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