Cationic Niosomes Research Articles

Development of FK506-loaded maleimide-functionalized cationic niosomes for prolonged retention and therapeutic efficacy in dry eye disease.

Tacrolimus (FK506) is widely used in ocular diseases such as corneal transplantation-host disease, uveitis, conjunctivitis, and dry eye disease (DED). However, its low aqueous solubility and poor ocular retention pose challenges for its application in the eye diseases. This study developed a novel FK506-loaded maleimide-functionalized cationic niosomes (FK506 M-CNS), aiming to prolong the retention time of FK506 in the eye and enhance its therapeutic efficacy. FK506 M-CNS had a particle size of 87.69 ± 1.05nm and zeta potential of 22.06 ± 1.01 mV. Results of histological evaluation through H&E staining and in vitro cytotoxicity of human corneal epithelial cells consistently revealed the excellent biocompatibility of FK506 M-CNS. FK506 M-CNS exhibited superior ocular retention compared to the market product Talymus®. FK506 M-CNS significantly alleviated the symptoms of DED and promoted the recovery of corneal epithelia. FK506 M-CNS group had the lowest expression levels of inflammatory factors associated with DED. These superiorities might be due to the electrostatic interaction between cationic niosomes and negatively charged mucin in the eye, and the covalent binding of maleimide with the thiol group in the mucin. The maleimide group improved the ocular retention and efficacy of FK506, but did not increase the toxicity. Results indicated that FK506 M-CNS had great potential as a nanopharmaceutical in the treatment of ocular diseases, and M-CNS could be a promising drug carrier for ophthalmic drug delivery systems.

Investigation on the structural and dynamical properties of cationic, anionic, and catanionic niosomes as multifunctional controlled drug delivery system for cabozantinib

BackgroundNiosomes are versatile nanocarriers for therapeutic compounds, and optimizing their structures via ionic surfactants can enhance their functionality considerably. Catanionic niosomes, which have the capability of both cationic and anionic niosomes, are attractive vehicles for drug delivery objectives. Here, we aim to design and evaluate catanionic niosome as a vehicle for anticancer agents. MethodsA molecular modeling pipeline was performed to model the physicochemical properties of cationic, anionic, and catanionic niosomes as a multifunctional drug delivery system for Cabozantinib. SPAN60 was used as the nonionic surfactant, cholesterol was the stabilizer, DOTAP and DCP were used as the cationic and anionic surfactants, respectively, and cabozantinib, an FDA-approved c-Met inhibitor was chosen as the drug compound. Some meaningful parameters relevant to the cabozantinib molecule and its characteristics in the bilayer, such as hydrogen bonding, total energy, the radius of gyration (Rgyr), mean square displacements (MSD), diffusion coefficient, and the radial distribution function (RDF) were evaluated and compared between the formulations. ResultsThe outcomes revealed that hydrogen bonding of cabozantinib is more probable with DOTAP, and the total energy of the drug is lower in anionic formulation (-180 kcal/mol). The MSD showed that cationic niosome restricts the movement of cabozantinib, while the drug could be efficiently released from the anionic niosome, and catanionic niosome can equilibrate the movement of the drug with a diffusion coefficient of 5.73 × 10−12 (m2/s). ConclusionsThis technique could effectively describe the behavior of drugs in various bilayer compositions, and the catanionic niosomes are potential multifunctional carriers for anticancer agents.

Preparation, Optimization and In vitro Evaluation of Doxorubicin-loaded into Hyaluronic Acid Coated Niosomes Against Breast Cancer.

Doxorubicin (DOX) is widely used against solid tumors. Niosomes are self-assembled nanocarriers of non-ionic surfactants. DOX loaded into cationic niosomes (DOX-Nio) was prepared via thin film hydration method. DOX-Nio was then decorated with a hyaluronic acid (DOX-HA-Nio) via electrostatic interaction. DOX-Nio and DOX-HA-Nio displayed a particle size of 120.0±1.02 and 182.9±2.3 nm, and charge of + 35.5±0.15 and -15.6±0.25 mV, respectively, with PDI < 0.3. DOX-HA-Nio showed a good stability regarding size and charge over 4 weeks at 4 °C and maintain their integrity after lyophilization. HPLC results showed a 94.1±4.2 % encapsulation efficiency of DOX with good entrapment and slow, prolonged DOX release even after 48 hrs. Cell viability assay showed an IC50 of 14.26 nM for the DOX-HA-Nio against MCF-7 cell line with micromolar IC50 results against CD-44 negative cell lines (NIH/3T3). DOX-HA-Nio was proven to be an effective, targeted nanocarrier for DOX against MCF-7 cell line.

Dual-Targeted Therapy in HER2-Overexpressing Breast Cancer with Trastuzumab and Novel Cholesterol-Based Nioplexes Silencing Mcl-1.

The challenge in HER2-overexpressing breast cancer therapy lies in creating an effective target therapy to overcome treatment resistance. Monoclonal antibodies and target gene silencing by siRNA are two potential strategies that have been widely developed for treating HER2-positive breast cancer. The siRNA delivery system is a crucial factor that influences siRNA therapy's success. In this study, lipid-based nanoparticles (cationic niosomes) composed of different cholesterol-based cationic lipids were formulated and characterized for delivering siRNA into HER2-overexpressing breast cancer cells. Niosomes containing a trimethylammonium headgroup showed the highest siRNA delivery efficiency with low toxicity. The myeloid cell leukemia-1 (Mcl-1) siRNA nioplex treatment significantly decreased mRNA expression and breast cancer cell growth. Dual-targeted therapy, consisting of treatment with an Mcl-1 siRNA nioplex and trastuzumab (TZ) solution, noticeably promoted cell-growth inhibition and apoptosis. The synergistic effect of dual therapy was also demonstrated by computer modeling software (CompuSyn version 1.0). These findings suggest that the developed cationic niosomes were effective nanocarriers for siRNA delivery in breast cancer cells. Furthermore, the Mcl-1 nioplex/TZ dual treatment establishes a synergistic outcome that may have the potential to treat HER2-overexpressing breast cancer.

Stability of polymeric cationic niosomes and their plasmid DNA-based complexes as gene delivery carriers

This study aims to explore the stability of lipo-polymeric niosomes/niosome-based pCMS-EGFP complexes under different storage temperatures (25 °C, 4 °C, and −20 °C). To date, the question of nucleic acid-complex stability is one of the most vital issues in gene delivery applications. The need for stable vaccines during the COVID-19 pandemic has merely highlighted it. In the case of niosomes as gene carriers, the scientific literature still lacks comprehensive stability studies. In this study, the physicochemical features of niosomes/nioplexes in terms of size, surface charge, and polydispersity index (PDI), along with transfection efficiency, and cytotoxicity in NT2 cells were evaluated for 8 weeks. Compared to day 0, the physicochemical features of the niosomes stored at 25 °C and −20 °C changed dramatically in terms of size, zeta potential, and PDI, while remaining in reasonable values when stored at 4 °C. However, niosomes and nioplexes stored at 4 °C and −20 °C showed nearly stable transfection efficiency values, yet an obvious decrease at 25 °C. This article provides a proof of concept into the stability of polymeric cationic niosomes and their nioplexes as promising gene delivery vehicles. Moreover, it highlights the practical possibility of storing nioplexes at 4 °C for up to 2 months, as an alternative to niosomes, for gene delivery purposes.

Formulation and Characterization of Epalrestat-Loaded Polysorbate 60 Cationic Niosomes for Ocular Delivery.

The aim of this work was to develop niosomes for the ocular delivery of epalrestat, a drug that inhibits the polyol pathway and protects diabetic eyes from damage linked to sorbitol production and accumulation. Cationic niosomes were made using polysorbate 60, cholesterol, and 1,2-di-O-octadecenyl-3-trimethylammonium propane. The niosomes were characterized using dynamic light scattering, zeta-potential, and transmission electron microscopy to determine their size (80 nm; polydispersity index 0.3 to 0.5), charge (-23 to +40 mV), and shape (spherical). The encapsulation efficiency (99.76%) and the release (75% drug release over 20 days) were measured with dialysis. The ocular irritability potential (non-irritating) was measured using the Hen's Egg Test on the Chorioallantoic Membrane model, and the blood glucose levels (on par with positive control) were measured using the gluc-HET model. The toxicity of the niosomes (non-toxic) was monitored using a zebrafish embryo model. Finally, corneal and scleral permeation was assessed with the help of Franz diffusion cells and confirmed with Raman spectroscopy. Niosomal permeation was higher than an unencapsulated drug in the sclera, and accumulation in tissues was confirmed with Raman. The prepared niosomes show promise to encapsulate and carry epalrestat through the eye to meet the need for controlled drug systems to treat the diabetic eye.

Chondrogenic Differentiation of Human Mesenchymal Stem Cells via SOX9 Delivery in Cationic Niosomes.

Gene transfer to mesenchymal stem cells constitutes a powerful approach to promote their differentiation into the appropriate cartilage phenotype. Although viral vectors represent gold standard vehicles, because of their high efficiency, their use is precluded by important concerns including an elevated immunogenicity and the possibility of insertional mutagenesis. Therefore, the development of new and efficient non-viral vectors is under active investigation. In the present study, we developed new non-viral carriers based on niosomes to promote the effective chondrogenesis of human MSCs. Two different niosome formulations were prepared by varying their composition on non-ionic surfactant, polysorbate 80 solely (P80), or combined with poloxamer 407 (P80PX). The best niosome formulation was proven to transfer a plasmid, encoding for the potent chondrogenic transcription factor SOX9 in hMSC aggregate cultures. Transfection of hMSC aggregates via nioplexes resulted in an increased chondrogenic differentiation with reduced hypertrophy. These results highlight the potential of niosome formulations for gene therapy approaches focused on cartilage repair.

Encapsulation of photosensitizer in niosomes for promotion of antitumor and antimicrobial photodynamic therapy

Photodynamic therapy (PDT) combines light with photosensitizers (PS) to produce reactive oxygen species (ROS) that can eliminate pathogenic microorganisms and tumor cells. Niosomes (NSs) are efficient nanocarriers and able to disperse insoluble drugs in water. Zinc phthalocyanine (ZnPc) is an excellent PS with water solubility problem that can be resolved by encapsulation in NSs. It is possible to apply PDT without inducing resistance to microorganisms or cells, since ROS interact in different cellular structures, such as proteins, lipid membranes and nucleic acids, avoiding the activation of resistance mechanisms. This work aims to develop NSs containing ZnPc to promote PDT against skin infections caused by pathogenic microorganisms and melanoma, the most severe type of skin cancer. Experimental planning was used to optimize the preparation of NSs with an average size of 233 ± 5.6 nm with PdI of 0.22 ± 0.07 nm and charge of −36.73 ± 0.65 mV, showing spherical and regular shape. Cationic NSs were also produced by surface modification of vesicles with chitosan and exhibited superior photobiological activity. NSs (anionic and cationic) containing ZnPc showed low dark cytotoxicity and intense photobiological activity after light irradiation. Antitumor and antimicrobial photobiological activities of NSs were tested on melanoma cells, methicillin-resistant Staphylococcus aureus (MRSA) and Candida albicans. The system showed excellent production of ROS in cell culture and apoptosis can be probably the main mechanism of cell death. The results show that NSs containing PS are versatile and can eliminate pathogenic microorganisms, such as bacteria and fungi of clinical interest and tumor cells.

Sphingolipid extracts enhance gene delivery of cationic lipid vesicles into retina and brain

The aim was to evaluate relevant biophysic processes related to the physicochemical features and gene transfection mechanism when sphingolipids are incorporated into a cationic niosome formulation for non-viral gene delivery to central nervous system. For that, two formulations named niosphingosomes and niosomes devoid of sphingolipid extracts, as control, were developed by the oil-in water emulsion technique. Both formulations and the corresponding complexes, obtained upon the addition of the reporter EGFP plasmid, were physicochemically and biologically characterized and evaluated. Compared to niosomes, niosphingosomes, and the corresponding complexes decreased particle size and increased superficial charge. Although there were not significant differences in the cellular uptake, cell viability and transfection efficiency increased when human retinal pigment epithelial (ARPE-19) cells were exposed to niosphingoplexes. Endocytosis via caveolae decreased in the case of niosphingoplexes, which showed higher co-localization with lysosomal compartment, and endosomal escape properties. Moreover, niosphingoplexes transfected not only primary central nervous system cells, but also different cells in mouse retina, depending on the administration route, and brain cortex. These preliminary results suggest that niosphingosomes represent a promising non-viral vector formulation purposed for the treatment of both retinal and brain diseases by gene therapy approach.

Design and Validation of a Process Based on Cationic Niosomes for Gene Delivery into Novel Urine-Derived Mesenchymal Stem Cells.

Background: Mesenchymal stem cells (MSCs) are stem cells present in adult tissues. They can be cultured, have great growth capacity, and can differentiate into several cell types. The isolation of urine-derived mesenchymal stem cells (hUSCs) was recently described. hUSCs present additional benefits in the fact that they can be easily obtained noninvasively. Regarding gene delivery, nonviral vectors based on cationic niosomes have been used and are more stable and have lower immunogenicity than viral vectors. However, their transfection efficiency is low and in need of improvement. Methods: We isolated hUSCs from urine, and the cell culture was tested and characterized. Different cationic niosomes were elaborated using reverse-phase evaporation, and they were physicochemically characterized. Then, they were screened into hUSCs for transfection efficiency, and their internalization was evaluated. Results: GPxT-CQ at a lipid/DNA ratio of 5:1 (w/w) had the best transfection efficiency. Intracellular localization studies confirmed that nioplexes entered mainly via caveolae-mediated endocytosis. Conclusions: In conclusion, we established a protocol for hUSC isolation and their transfection with cationic niosomes, which could have relevant clinical applications such as in gene therapy. This methodology could also be used for creating cellular models for studying and validating pathogenic genetic variants, and even for performing functional studies. Our study increases knowledge about the internalization of tested cationic niosomes in these previously unexplored cells.

Synergistic Effect of Doxorubicin and siRNA-Mediated Silencing of Mcl-1 Using Cationic Niosomes against 3D MCF-7 Spheroids.

Chemotherapy is a vital option for cancer treatment; however, its therapeutic outcomes are limited by dose-dependent toxicity and the occurrence of chemoresistance. siRNAs have emerged as an attractive therapeutic option enabling specific interference with target genes. Combination therapy using chemotherapeutic agents along with gene therapy could be a potential strategy for cancer management, which not only improves therapeutic efficacy but also decreases untoward effects from dose reduction. In this study, a cationic niosome containing plier-like cationic lipid B was used to convey siRNA against anti-apoptotic mRNA into MCF-7 and MDA-MB-231 cells. Mcl-1 silencing markedly decreased the viability of MCF-7 cells and triggered apoptosis. Moreover, computer modeling suggested that the combination of doxorubicin (Dox) and Mcl-1 siRNA exhibited a synergistic relationship and enabled a dose reduction of each agent at 1.71 and 3.91 folds, respectively, to reach a 90% inhibitory effect when compared to single-agent treatments. Synergistic antitumor activity was further verified in a 3D spheroid culture which revealed, in contrast to single-agent treatment, the combination markedly decreased spheroid volume over time. Together, the combination therapy between Mcl-1 silencing and Dox exhibits a synergistic effect that may be exploited for novel breast cancer treatment.

Co-delivery of miRNA-15a and miRNA-16-1 using cationic PEGylated niosomes downregulates Bcl-2 and induces apoptosis in prostate cancer cells.

Tumor suppressor miRNAs, miR-15a and miR-16-1, with high-specificity and oncogenic targeting of Bcl-2, can target tumor tissues. Disadvantages of the clinical application of free miRNAs include poor cellular uptake and instability in plasma, which can be partially improved by using nanocarriers to deliver anti-cancer agents to the tumor cell. In this study, cationic niosomes were designed and optimized with the specific formulation. Then, the physical characteristics, the cytotoxicity, the impact of transfected miRNAs on the expression of the Bcl-2 gene, and the apoptosis rate of the different formulation into prostate cancer cell were determined. The optimum formulation containing tween-60: cholesterol: DOTAP: DSPE-PEG2000 at 70:30:25:5 demonstrated that the vesicle size and zeta potentials were 69.7nm and + 14.83mV, respectively. Additionally, noisome-loaded miRNAs had higher toxicity against cancer cells comparing with free forms. The transfection of PC3 cells with the combination therapy of nanocarriers loaded of two miRNAs led to a significant decrease in the expression of the Bcl-2 gene and increased the degree of cell death in PC3 cells compared with other treatment groups, and the synergistic effects of co-delivery of miR-15a and miR-16-1 on prostate cancer cells were shown. According to the results, it seems the designed niosomes containing miR-15a and miR-16-1 can target the Bcl-2 gene and provide a cheap, applicable, cost-effective, and safe drug delivery system against prostate cancer.

Promising Antifungal Potential of Engineered Non-ionic Surfactant-Based Vesicles: In Vitro and In Vivo Studies.

Fungal keratitis (FK) is a corneal infection caused by different fungal species. It is treated by the topical application of natamycin (NAT). Nevertheless, this approach faces many limitations like toxic effects, frequent dosing, resistance, and patient discomfort. The present research reports the development of trimethyl chitosan (TMC) coated mucoadhesive cationic niosomes by a modified thin-film hydration method. TMC was synthesized using a one-step carbodiimide method and characterized by 1H-NMR and degree of quaternization (53.74 ± 1.06%). NAT, cholesterol (CHOL), span 60 (Sp60), and dicetyl phosphate (DCP) were used to prepare niosomes which were incubated with TMC to obtain mucoadhesive cationic NAT loaded niosomes (MCNNs). MCNNs showed a spherical shape with 1031.12 ± 14.18nm size (PDI below 0.3) and 80.23 ± 5.28% entrapment efficiency. In vitro drug release studies showed gradual drug release from TMC coated niosomes as compared to the uncoated niosomes. MIC assay and disk diffusion assay revealed promising in vitro antifungal potential of MCNNs similar to the marketed formulation. For investigating in vivo performance, ocular retention and pharmacokinetics, ocular irritation, and ulcer healing studies were performed using the rabbit model. Mucoadhesive property and prolonged local drug release improved the safety and efficacy of NAT, suggesting that the developed niosomes could be an emerging system for effective treatment of fungal keratitis.

Brain Angiogenesis Induced by Nonviral Gene Therapy with Potential Therapeutic Benefits for Central Nervous System Diseases.

Gene therapy employing nanocarriers represents a promising strategy to treat central nervous system (CNS) diseases, where brain microvasculature is frequently compromised. Vascular endothelial growth factor (VEGF) is a key angiogenic molecule; however, its in vivo administration to the CNS by nonviral gene therapy has not been conducted. Hence, we prepared and physicochemically characterized four cationic niosome formulations (1-4), which were combined with pVEGF-GFP to explore their capacity to transfer the VEGF gene to CNS cells and achieve angiogenesis in the brain. Experiments in primary neuronal cells showed successful and safe transfection with niosome 4, producing double levels of biologically active VEGF in comparison to the rest of the formulations. Intracortical administration of niosome 4 based nioplexes in mouse brain validated the ability of this nonviral vector to deliver the VEGF gene to CNS cells, inducing brain angiogenesis and emerging as a promising therapeutic approach for the treatment of CNS diseases.

Effect of hydrophobic tails of plier-like cationic lipids on nucleic acid delivery and intracellular trafficking.

In the optimization of transfection efficacy, one of the crucial barriers to effective gene delivery is in fact the intracellular trafficking of nucleic acids, besides the first and the last steps of gene transfer, i.e., delivery to the cell and transcription. Modifications of cationic lipid structure have been reported to have a significant effect on gene delivery. Therefore, the plier-like cationic lipids (PCLs) have been synthesized and the effect of the different types of hydrophobic tails (chain length and unsaturated hydrocarbon) on physicochemical properties, cellular uptake, trafficking process, transfection, and silencing efficiency has been investigated. In this study, the plier-like cationic niosomes (PCNs) containing PCL (A, B, and C) were evaluated their performance to deliver pDNA and siRNA to HeLa cells. Among the PCNs, PCN-B with saturated asymmetric hydrocarbon tails (C18 and C12) provided the highest efficiency for pDNA and siRNA delivery. Furthermore, the results revealed that the structure of the cationic lipids affected the internalization pathway and the intracellular trafficking. PCL-B and PCL-C with asymmetric tails preferred clathrin- and caveolae-mediated endocytosis as the predominant internalization pathways and were also involved in the polymerization process for transfection. However, PCL-A with symmetry hydrocarbon tails (C12) was predominantly taken up via macropinocytosis. All PCNs were able to escape from endosomal-lysosomal systems through facilitation of acidification. Results obtained from the cytotoxicity test revealed that the PCNs were safe in vitro. Therefore, PCNs provide a great prospect as an alternative effective gene delivery system.

Cationic niosome-based hBMP7 gene transfection of neuronal precursor NT2 cells to reduce the migration of glioma cells in vitro

This study explores interesting complementary approaches in cell-based hBMP7 gene delivery in order to mitigate the migration of glioblastoma cells based on the idea that this human bone morphogenetic protein (hBMP7) has enormous therapeutic potential in curing brain injuries as well as malignancies. After physicochemical characterization, the non-viral cationic niosomes were complexed with pUNO1-hBMP7 plasmids and used to transfect neuronal precursor NT2 cells. Subsequently, the transfected cells were co-cultured with glioma C6 cells to determine their antitumor effect in vitro. However the co-culture with either untransfected/transfected NT2 cells may reduce the viability of C6 glioma cells, the hBMP7-overexpressing NT2 cells hamper the migration of C6 glioma cells. These results highlight the potential of NT2 cell-based delivery of hBMP7 for impeding the metastasis of glioma cells.

PEGylated Plier-Like Cationic Niosomes on Gene Delivery in HeLa Cells

Lipid-based formulations have been used as a widespread carrier to improve gene delivery. Niosomes, one type of lipid-based vesicular systems are produced from non-ionic surfactants which are generally inexpensive and potentially more stable than phospholipids. This article was to develop PEGylated cationic niosomes for DNA delivery. Thin film hydration and sonication method were applied for cationic niosomes. The niosome formulations were composed of Span 20, cholesterol (Chol) and plier-like cationic lipid B (PCL-B) with or without cholesterol-polyethylene glycol 2000 (Chol-PEG). The physicochemical properties of cationic niosomes and nioplexes were evaluated including particle size, zeta potential, DNA condensation and serum protection. The transfection efficiency and cell viability were examined in HeLa cells. The particle size and surface charge of PEGylated cationic niosome containing Span 20: Chol: PCL-B: Chol-PEG at the molar ratio of 2.5: 2.5: 1.5: 0.14 (N-PEG2) were 129.47 ± 2.15 nm and 25.93 ± 4.18 mV, respectively. These PEGylated cationic niosomes could condense pDNA into the nanosize particles and also enhance the serum protection ability for at least 6 h. Moreover, N-PEG2 exhibited high transfection efficiency in comparison with lipofectamine® 2000 and low cytotoxicity. Therefore, the novel PEGylated cationic niosomes have the capability to develop as a promising potential carrier for DNA delivery.

Niosomes Containing Spermine-Based Cationic Lipid with Different Linkers for siRNA Delivery

Niosomes are a lipid nanoparticle which have been widely used as non-viral carrier for therapeutic DNA or siRNA. They are formulated from non-ionic surfactant and other helper lipids. The aim of this study were to formulate niosome containing spermine-based cationic lipid with different linkers and to evaluate the efficiency of siRNA delivery in cervical cancer cell (HeLa cell). The niosomes were formulated from cholesterol (Chol), Span 20 and different cationic lipid (Ay, By, Cy and Dy) at various molar ratios. The properties of niosomes and ability of niosome to complex with siRNA were characterized. The cellular uptake, gene silencing efficiency and cytotoxicity were also determined. From the results, niosomes formulated at Chol:Span20:lipid molar ratio of 2.5:2.5:2 showed positive zeta potential and they were in nanosize (&lt;200 nm). The binding ability of cationic niosomes to siRNA depended on types of cationic lipid. Among niosome/siRNA complexes, the niosome By/siRNA complex provided the highest gene silencing efficiency at weight ratio of 20. The highest cellular uptake also obtained by using niosome By as a carrier. The cytotoxicity revealed that cationic niosomes had low toxicity (cell viability &gt; 80%). In conclusion, the cationic niosomes prepared from Chol, Span 20 and spermine-based cationic lipids are able to complex with siRNA and suitable for siRNA delivery with low toxicity.

Gene delivery to the rat retina by non-viral vectors based on chloroquine-containing cationic niosomes

The incorporation of chloroquine within nano formulations, rather than as a co-treatment of the cells, could open a new avenue for in vivo retinal gene delivery. In this manuscript, we evaluated the incorporation of chloroquine diphosphate into the cationic niosome formulation composed of poloxamer 188, polysorbate 80 non-ionic surfactants, and 2,3-di (tetradecyloxy) propan-1-amine (hydrochloride salt) cationic lipid, to transfect rat retina. Niosome formulations without and with chloroquine diphosphate (DPP80, and DPP80-CQ, respectively) were prepared by the reverse phase evaporation technique and characterized in terms of size, PDI, zeta potential, and morphology. After the incorporation of the pCMS-EGFP plasmid, the resultant nioplexes -at different cationic lipid/DNA mass ratios- were further evaluated to compact, liberate, and secure the DNA against enzymatic digestion. In vitro procedures were achieved in ARPE-19 cells to assess transfection efficacy and intracellular transportation. Both nioplexes formulations transfected efficiently ARPE-19 cells, although the cell viability was clearly better in the case of DPP80-CQ nioplexes. After subretinal and intravitreal injections, DPP80 nioplexes were not able to transfect the rat retina. However, chloroquine containing vector showed protein expression in many retinal cells, depending on the administration route. These data provide new insights for retinal gene delivery based on chloroquine-containing niosome non-viral vectors.

A novel plier-like gemini cationic niosome for nucleic acid delivery

This study aimed to develop a novel cationic niosome formulation from a novel plier-like cationic lipid A (PCL-A) with Span 20 and cholesterol (Chol). The niosomes were prepared by a thin film hydration method followed by probe sonication. The molar ratios of the cationic lipid in the formulation, and the weight ratios of the cationic niosomes to the nucleic acids (pDNA or siRNA) were optimized. The physical properties of the niosome were investigated. In addition, the cytotoxicity, transfection efficiency, gene silencing efficiency, cellular uptake, and cellular uptake pathway were also determined. The results revealed that the cationic niosomes containing PCL-A: Span20: Chol at the molar ratio of 1.5: 2.5: 2.5 (N1.5) and 2: 2.5: 2.5 (N2) were optimal for DNA and siRNA delivery, respectively. The high transfection efficiency of about 97% was obtained form N1.5/DNA at the weight ratio of 1: 1. In addition, the efficiency of gene silencing obtained from the complexes of N2/siRNA at the weight ratio of 5: 1 was higher than that of the commercial product without affecting the cell viability. Therefore, these novel cationic niosomes could be a promising potential carrier for DNA and siRNA delivery.