Oxime-functionalized anti-insecticide fabric reduces insecticide exposure through dermal and nasal routes, and prevents insecticide-induced neuromuscular-dysfunction and mortality.

Farmers from South Asian countries spray insecticides without protective gear, which leads to insecticide exposure through dermal and nasal routes. Acetylcholinesterase plays a crucial role in controlling neuromuscular function. Organophosphate and carbamate insecticides inhibit acetylcholinesterase, which leads to severe neuronal/cognitive dysfunction, breathing disorders, loss of endurance, and death. To address this issue, an Oxime-fabric is developed by covalently attaching silyl-pralidoxime to the cellulose of the fabric. The Oxime-fabric, when stitched as a bodysuit and facemask, efficiently deactivates insecticides (organophosphates and carbamates) upon contact, preventing exposure. The Oxime-fabric prevents insecticide-induced neuronal damage, neuro-muscular dysfunction, and loss of endurance. Furthermore, we observe a 100% survival rate in rats when repeatedly exposed to organophosphate-insecticide through the Oxime-fabric, while no survival is seen when organophosphate-insecticide applied directly or through normal fabric. The Oxime-fabric is washable and reusable for at least 50 cycles, providing an affordable solution to prevent insecticide-induced toxicity and lethality among farmers.

Mitigation of pesticide-mediated ocular toxicity via nanotechnology-based contact lenses: a review.

The xenobiotic stress exerted by pesticides leads to the deterioration of human and animal health including ocular health. Acute or prolonged exposure to these agricultural toxicants has been implicated in a number of pathological conditions of the eye such as irritation, epiphora or hyper-lacrimation, abrasions on the ocular surface, and decreased visual acuity. The issue is compounded by the fact that tissues of the eye absorb pesticides faster than other organs of the body and are more susceptible to damage as well. However, there is a lacuna in our knowledge regarding the ways by which pesticide exposure-mediated ocular insult might be counteracted. Topical instillation of drugs known to combat the pesticide induced toxicity has been explored to mitigate the detrimental impact of pesticide exposure. However, topical eye drop solutions exhibit very low bioavailability and limited drug residence duration in the tear film decreasing their efficacy. Contact lenses have been explored in this respect to increase bioavailability of ocular drugs, while nanoparticles have lately been utilized to increase drug bioavailability and increase drug residence duration in different tissues. The current review focuses on drug delivery and futuristic aspects of corneal protection from ocular toxicity using contact lenses.

Gemini Lipopeptide Bearing an Ultrashort Peptide for Enhanced Transfection Efficiency and Cancer-Cell-Specific Cytotoxicity.

Cationic gemini lipopeptides are a relatively new class of amphiphilic compounds to be used for gene delivery. Through the possibility of incorporating short peptides with cell-penetrating functionalities, these lipopeptides may be advantageous over traditional cationic lipids. Herein, we report the design, synthesis, and application of a novel cationic gemini lipopeptide for gene delivery. An ultrashort peptide, containing four amino acids, arginine-cysteine-cysteine-arginine, serves as a cationic head group, and two α-tocopherol moieties act as hydrophobic anchoring groups. The new lipopeptide (ATTA) is incorporated into the conventional liposomes, containing 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 1,2-dioleoyl-sn-glycerol-3-phosphoethanolamine (DOPE), at different molar ratios. The formulated liposomes are characterized and screened for better transfection efficiency. Transfection activity in multiple human cell lines from cancerous and noncancerous origins indicates that the inclusion of an optimal ratio of ATTA in the liposomes substantially enhances the transfection efficiency, superior to that of a traditional liposome, DOTAP-DOPE. Cytotoxicity of ATTA-containing formulations against multiple cell lines indicates potentially distinct activity between cancer and noncancer cell lines. Furthermore, lipoplexes of the ATTA-containing formulations with anticancer therapeutic gene, plasmid encoding tumor necrosis factor-related apoptosis-inducing ligand (pTRAIL), induce obviously more cytotoxicity than conventional formulations. The results indicate that arginine-rich cationic lipopeptide appears to be a promising ingredient in gene delivery vector formulations to enhance transfection efficiency and cell-selective cytotoxicity.

Arginine-tocopherol bioconjugated lipid vesicles for selective pTRAIL delivery and subsequent apoptosis induction in glioblastoma cells.

The incorporation of specific therapeutic gene into glioblastoma offers potent therapeutic strategy to treat the disease. Non-viral gene delivery vectors are of particular interest due to their tuneable transfection efficiency and easy scale-up. Herein, we demonstrate successful delivery of plasmid encoding tumor necrosis factor (TNF)-related apoptosis-inducing ligand (pTRAIL) using arginine-conjugated tocopherol lipid (AT) nanovesicles into glioblastoma cell lines. Another cationic lipid, glycine-conjugated tocopherol lipid (GT) having glycine in the head group region is also synthesized as a control lipid. Both lipid-derived liposomes effectively condensed the pDNA and the corresponding biomacromolecular assemblies (lipoplexes) are efficiently transfected into different cell lines. AT-based liposomes exhibit higher transfection efficacy in various cell lines, particularly selective in glioma cell lines. At an optimized N/P ratio, both the liposomal formulations show low cytotoxicity. AT-based lipoplexes have superior cellular uptake in U87 than the control lipid GT. The expression of TRAIL protein regulated death receptor and apoptosis signaling pathway is assayed by western blot using transfection of AT-based/pTRAIL into U87 cell lines. Induction of apoptosis in U87 cells exposed to AT-based/pTRAIL plasmid is evaluated by MTT assay as well as Annexin V-propidium iodide dual-staining assay. All results indicate that the developed AT-based/pTRAIL system offers a potentially safe and efficient therapeutic strategy for glioblastoma gene therapy.

α-Tocopherol-anchored gemini lipids with delocalizable cationic head groups: the effect of spacer length on DNA compaction and transfection properties.

Understanding the role of structural units in cationic lipids used for gene delivery is essential in designing efficient gene delivery vehicles. Herein, we report a systematic structure-activity investigation on the influence of the spacer length on the DNA compaction ability and the transfection properties of gemini lipids with delocalizable cationic head groups. We have synthesized a series of dimeric cationic lipids varying in spacer length. The DNA binding interactions of liposomal formulations were characterized by gel electrophoresis and ethidium bromide (EtBr) exclusion assays. Condensation potentials were optimized and the best results were observed with cationic lipids possessing a 6 methylene spacer (TIM 6). We found that the size of the lipid/DNA complex decreased with the increase in spacer chain length up to a 6 methylene spacer TIM 6 and increased further. We have optimized the dimeric lipid/DOPE molar formulation using the ß-galactosidase activity assay and found that the molar ratio of 1 : 1.5 (gemini lipid/DOPE) showed the maximum transfection among all molar ratios. The cellular uptake and co-localization of lipoplexes were observed by cell analysis and imaging using confocal microscopy. The results confirm that the lipoplex derived from lipid TIM 6 and pCMV-bgal/DNA internalizes via cellular endocytosis. The cytotoxicity studies using the MTT assay revealed that all formulations show comparable cell viability to the commercial standard even at higher charge ratios. Overall, the data suggest that the DNA compaction ability of these lipid dimers depends on the spacer chain length and the gemini lipid containing a six methylene aliphatic spacer has the maximum potential to deliver genes.

Evolution of New "Bolaliposomes" using Novel α-Tocopheryl Succinate Based Cationic Lipid and 1,12-Disubstituted Dodecane-Based Bolaamphiphile for Efficient Gene Delivery.

Nonviral lipid-based vectors are promising transporting systems for the intracellular delivery of therapeutic gene sequences and directly influence the success of gene delivery. However, the associated drawbacks like lower transfection, toxicity, and targetability require further improvement. Thus, herein, we report a novel lipid formulation by the mixing of two distinct cationic surfactants such as tocopheryl succinate based cationic lipid and 1,12 dodecane based bolaamphiphile and prove it to be a good transfection reagent with its competing potential with the "golden standard", Lipofectamine 3000 (L3K). These interesting aggregations were named "Bolaliposome" and showed adequate unilamellar vesicle morphology under transmission electron microscopy, having a size of around 100 nm and could transfect efficiently different varieties of cell lines. Moreover, the generated complexes from bolaliposome and DNA (bolalipoplex) were characterized in terms of surface potential, hydrodynamic size, and gel electrophoresis. Various pharmacological inhibitors were also used in reporter gene expression to prove that the complexes followed the clathrin-mediated endocytosis. Finally, these findings would be helpful in the making of new aggregates and the development of better cytofectins. This was developed by optimizing the formulation based on the efficiency of reporter gene expression performed using the pEGFP-N3 plasmid.