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1.
Biomolecules ; 13(11)2023 11 13.
Article in English | MEDLINE | ID: mdl-38002329

ABSTRACT

BACKGROUND: Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. METHODS: Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. RESULTS: The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. CONCLUSIONS: These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.


Subject(s)
Nanoparticles , Thyroid Neoplasms , Humans , Animals , Mice , Polylactic Acid-Polyglycolic Acid Copolymer , Cetuximab , Lactic Acid , Polyglycolic Acid , Glycols , Tissue Distribution , Iodine Radioisotopes , Quality of Life , Cell Line, Tumor , Thyroid Neoplasms/drug therapy , ErbB Receptors , Drug Carriers
3.
Int J Pharm ; 639: 122968, 2023 May 25.
Article in English | MEDLINE | ID: mdl-37080363

ABSTRACT

Nanodiamonds were combined with niosome, and resulting formulations were named as nanodiasomes, which were evaluated in terms of physicochemical features, cellular internalization, cell viability and transfection efficiency both in in vitro and in in vivo conditions. Such parameters were analyzed at 4 and 25 °C, and at 15 and 30 days after their elaboration. Nanodiasomes showed a particle size of 128 nm that was maintained over time inside the ± 10% of deviation, unless after 30 days of storage at 25 °C. Something similar occurred with the initial zeta potential value, 35.2 mV, being both formulations more stable at 4 °C. The incorporation of nanodiamonds into niosomes resulted in a 4-fold increase of transfection efficiency that was maintained over time at 4 and 25 °C. In vivo studies reported high transgene expression of nanodiasomes after subretinal and intravitreal administration in mice, when injected freshly prepared and after 30 days of storage at 4 °C.


Subject(s)
Nanodiamonds , Rats , Mice , Animals , Rats, Sprague-Dawley , Cell Line , Retina/metabolism , Liposomes , Lipids
4.
Cell Biosci ; 13(1): 44, 2023 Mar 04.
Article in English | MEDLINE | ID: mdl-36871010

ABSTRACT

In recent years, progress in nanotechnology provided new tools to treat cancer more effectively. Advances in biomaterials tailored for drug delivery have the potential to overcome the limited selectivity and side effects frequently associated with traditional therapeutic agents. While autophagy is pivotal in determining cell fate and adaptation to different challenges, and despite the fact that it is frequently dysregulated in cancer, antitumor therapeutic strategies leveraging on or targeting this process are scarce. This is due to many reasons, including the very contextual effects of autophagy in cancer, low bioavailability and non-targeted delivery of existing autophagy modulatory compounds. Conjugating the versatile characteristics of nanoparticles with autophagy modulators may render these drugs safer and more effective for cancer treatment. Here, we review current standing questions on the biology of autophagy in tumor progression, and precursory studies and the state-of-the-art in harnessing nanomaterials science to enhance the specificity and therapeutic potential of autophagy modulators.

6.
ACS Appl Mater Interfaces ; 14(11): 13665-13677, 2022 Mar 23.
Article in English | MEDLINE | ID: mdl-35289181

ABSTRACT

Nanodiamonds (NDs) are promising materials for gene delivery because of their unique physicochemical and biological features, along with their possibility of combination with other nonviral systems. Our aim was to evaluate the biophysical performance of NDs as helper components of niosomes, named nanodiasomes, to address a potential nonviral gene delivery nanoplatform for therapeutic applications in central nervous system (CNS) diseases. Nanodiasomes, niosomes, and their corresponding complexes, obtained after genetic material addition at different ratios (w/w), were evaluated in terms of physicochemical properties, cellular uptake, intracellular disposition, biocompatibility, and transfection efficiency in HEK-293 cells. Nanodiasomes, niosomes, and complexes fulfilled the physicochemical features for gene therapy applications. Biologically, the incorporation of NDs into niosomes enhanced 75% transfection efficiency (p < 0.001) and biocompatibility (p < 0.05) to values over 90%, accompanied by a higher cellular uptake (p < 0.05). Intracellular trafficking analysis showed higher endocytosis via clathrins (p < 0.05) in nanodiaplexes compared with nioplexes, followed by higher lysosomal colocalization (p < 0.05), that coexisted with endosomal escape properties, whereas endocytosis mediated by caveolae was the most efficient pathway in the case of nanodiaplexes. Moreover, studies in CNS primary cells revealed that nanodiaplexes successfully transfected neuronal and retinal cells. This proof-of-concept study points out that ND integration into niosomes represents an encouraging nonviral nanoplatform strategy for the treatment of CNS diseases by gene therapy.


Subject(s)
Central Nervous System Diseases , Nanodiamonds , Genetic Therapy , HEK293 Cells , Humans , Liposomes/chemistry , Plasmids
7.
Colloids Surf B Biointerfaces ; 209(Pt 2): 112170, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34740093

ABSTRACT

Natural nasal spray formulations were prepared by using Zingiber officinalis (Z. officinalis) extract and citral synergically loaded into specifically designed phospholipid vesicles. Phospholipid vesicles were selected according to their stabilizing effect on the nasal mucosal barrier, and their effectiveness was further potentiated by the co-loading of Z. officinalis extract as antioxidant and anti-inflammatory agent, and citral as antibacterial molecule. Cryo-TEM images confirmed the formation of morphologically homogeneous and small vesicles, sized around 100 nm, negatively charged (-44 mV) and highly biocompatible (viability ≥100%) as detected by using epithelial cells. The analysis of size distribution of sprayed droplets, average velocity module and spray cone angle suggested a good aptitude of the vesicles to be nebulized and their effective deposition in the nasal cavity. Moreover, vesicles were effectively capable of inhibiting some nasal pathogenic bacteria (i.e. Streptococcus pyogenes, Staphylococcus aureus, Escherichia coli) and to protect the epithelial cells against oxidative damage. The formulations are natural and safe, and all of them have shown promising technological and biological properties suggesting their possible application in the nasal cavity for the treatment of congestions and non-allergic rhinitis.


Subject(s)
Antioxidants , Phospholipids , Acyclic Monoterpenes , Plant Extracts/pharmacology
8.
Pharmaceutics ; 13(12)2021 Nov 23.
Article in English | MEDLINE | ID: mdl-34959270

ABSTRACT

Inhalation therapy offers several advantages in respiratory disease treatment. Azithromycin is a macrolide antibiotic with poor solubility and bioavailability but with a high potential to be used to fight lung infections. The main objective of this study was to generate a new inhalable dry powder azithromycin formulation. To this end, an electrospray was used, yielding a particle size around 2.5 µm, which is considered suitable to achieve total deposition in the respiratory system. The physicochemical properties and morphology of the obtained microparticles were analysed with a battery of characterization techniques. In vitro deposition assays were evaluated after aerosolization of the powder at constant flow rate (100 L/min) and the consideration of the simulation of two different realistic breathing profiles (healthy and chronic obstructive pulmonary disease (COPD) patients) into a next generation impactor (NGI). The formulation was effective in vitro against two types of bacteria, Staphylococcus aureus and Pseudomonas aeruginosa. Finally, the particles were biocompatible, as evidenced by tests on the alveolar cell line (A549) and bronchial cell line (Calu-3).

9.
Molecules ; 26(21)2021 Nov 04.
Article in English | MEDLINE | ID: mdl-34771079

ABSTRACT

The extract of Cardiospermum halicacabum L. (C. halicacabum) obtained from flower, leaf and vine was loaded into modified phospholipid vesicles aiming at obtaining sprayable, biocompatible and effective nasal spray formulations for the treatment of nasopharyngeal diseases. Penetration enhancer-containing vesicles (PEVs) and hyalurosomes were formulated, and stabilized by adding a commercial gelatin from fish (20 mg/mL) or chondroitin sulfate from catshark cartilages (Scyliorhinus canicula, 20 mg/mL). Cryo-TEM images confirmed the formation of spherical vesicles, while photon correlation spectroscopy analysis disclosed the formation of small and negatively-charged vesicles. PEVs were the smaller vesicles (~100 nm) along with gelatin-hyalurosomes (~120 nm), while chondroitin-PEVs and chondroitin-hyalurosomes were larger (~160 nm). Dispersions prepared with chondroitin sulfate were more homogeneous, as the polydispersity index was ~0.15. The in vitro analysis of the droplet size distribution, average velocity module and spray cone angle suggested a good spray-ability and deposition of formulations in the nasal cavity, as the mean diameter of the droplets was in the range recommended by the Food and Drug Administration for nasal targets. The spray plume analysis confirmed the ability of PEVs, gelatin-PEVs, hyalurosomes and gelatin-hyalurosomes to be atomized in fine droplets homogenously distributed in a full cone plume, with an angle ranging from 25 to 30°. Moreover, vesicles were highly biocompatible and capable of protecting the epithelial cells against oxidative damage, thus preventing the inflammatory state.


Subject(s)
Chondroitin Sulfates , Gelatin , Liposomes , Nasal Sprays , Phospholipids , Plant Extracts/administration & dosage , Sapindaceae/chemistry , Aerosols , Antioxidants/administration & dosage , Antioxidants/chemistry , Biocompatible Materials/chemistry , Chemical Phenomena , Drug Compounding , Humans , Keratinocytes/drug effects , Oxidative Stress/drug effects , Particle Size , Plant Extracts/chemistry
10.
Eur J Pharm Biopharm ; 169: 103-112, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34606927

ABSTRACT

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.


Subject(s)
Brain , Gene Transfer Techniques , Genetic Vectors/biosynthesis , Liposomes/pharmacology , Retinal Pigment Epithelium , Sphingolipids/pharmacology , Animals , Brain/metabolism , Brain/pathology , Cell Survival , Complex Mixtures/pharmacology , Emulsions/pharmacology , Genetic Therapy/methods , Humans , Mice , Plasmids , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/pathology
11.
Antioxidants (Basel) ; 10(7)2021 Jul 11.
Article in English | MEDLINE | ID: mdl-34356342

ABSTRACT

A total green nanotechnological nasal spray has been manufactured and proposed as an alternative treatment of rhinitis and rhinosinusitis. It was obtained by combining the strengthening effect of liposomes on barrier function, the hydrating and lubricating properties of sodium hyaluronan and the anti-inflammatory and antioxidant activities of the extract of Zingiber officinalis. To this purpose, the extract was loaded in special phospholipid vesicles immobilized with hyaluronic acid (hyalurosomes), which were further enriched with glycerol in the water phase. Liposomes and glycerosomes were prepared as well and used as reference. Vesicles were oligolamellar and multicompartment, as confirmed by cryogenic transmission electron microscopy (cryo-TEM) observation, small in size (~140 nm) and negatively charged (~-23 mV). Spray characteristics were evaluated by using the Spraytec® and instant images, from which the plume angle was measured. The range of the droplet size distribution and the narrow spray angle obtained suggest a good nebulization and a possible local deposition in the nasal cavity. In vitro studies performed by using human keratinocytes confirmed the high biocompatibility of vesicles and their ability to effectively counteract oxidative damage on cells induced by hydrogen peroxide. The overall collected data suggest that our vesicles are suitable as nasal spray.

12.
J Control Release ; 335: 619-636, 2021 07 10.
Article in English | MEDLINE | ID: mdl-34116135

ABSTRACT

The development of cell microencapsulation systems began several decades ago. However, today few systems have been tested in clinical trials. For this reason, in the last years, researchers have directed efforts towards trying to solve some of the key aspects that still limit efficacy and biosafety, the two major criteria that must be satisfied to reach the clinical practice. Regarding the efficacy, which is closely related to biocompatibility, substantial improvements have been made, such as the purification or chemical modification of the alginates that normally form the microspheres. Each of the components that make up the microcapsules has been carefully selected to avoid toxicities that can damage the encapsulated cells or generate an immune response leading to pericapsular fibrosis. As for the biosafety, researchers have developed biological circuits capable of actively responding to the needs of the patients to precisely and accurately release the demanded drug dose. Furthermore, the structure of the devices has been subject of study to adequately protect the encapsulated cells and prevent their spread in the body. The objective of this review is to describe the latest advances made by scientist to improve the efficacy and biosafety of cell microencapsulation systems for sustained drug delivery, also highlighting those points that still need to be optimized.


Subject(s)
Cell Encapsulation , Containment of Biohazards , Alginates , Capsules , Drug Compounding , Glucuronic Acid , Hexuronic Acids , Humans , Microspheres
13.
Drug Discov Today ; 26(3): 852-861, 2021 03.
Article in English | MEDLINE | ID: mdl-33242694

ABSTRACT

In recent years, cell microencapsulation technology has advanced, mainly driven by recent developments in the use of stem cells or the optimization of biomaterials. Old challenges have been addressed from new perspectives, and systems developed and improved for decades are now being transferred to the market by novel start-ups and consolidated companies. These products are mainly intended for the treatment of diabetes mellitus (DM), but also cancer, central nervous system (CNS) disorders or lysosomal diseases, among others. In this review, we analyze the results obtained in clinical trials to date and define the global key players that will lead the cell microencapsulation market to bring this technology to the clinic in the future.


Subject(s)
Biocompatible Materials/administration & dosage , Cell Encapsulation/methods , Drug Delivery Systems , Biomedical Technology/methods , Capsules , Delayed-Action Preparations , Humans , Stem Cells/cytology
14.
Pharmaceutics ; 12(11)2020 Oct 23.
Article in English | MEDLINE | ID: mdl-33113923

ABSTRACT

An extract of Hypericum scruglii, an endangered endemic plant of Sardinia (Italy), was prepared and characterized. It was loaded in special phospholipid vesicles, glycerosomes, which were modified by adding maltodextrin (glucidex) and a polymer (gelatin or hyaluronan). The corresponding liposomes were also prepared and used as reference. The vesicles disclosed suitable physicochemical features for skin delivery. Indeed, their mean diameter ranged from 120 to 160 nm, they were homogeneously dispersed (polydispersity index ≤ 0.30), and their zeta potential was highly negative (~-45 mV). The vesicle dispersions maintained unchanged characteristics during 60 days of storage, were highly biocompatible, and were able to protect keratinocytes against damages due to oxidative stress induced by treating them with hydrogen peroxide. Vesicles were also capable of promoting cell proliferation and migration in vitro by means of a scratch wound assay. The results confirmed the fruitful delivery of the extract of H. scruglii in glycerosomes modified with glucidex and gelatin and their promising ability for skin protection and treatment.

15.
Int J Pharm ; 588: 119757, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-32791297

ABSTRACT

Gene therapy strategies based on non-viral vectors are currently considered as a promising therapeutic option for the treatment of cystic fibrosis (CF), being liposomes the most commonly used gene carriers. Niosomes offer a powerful alternative to liposomes due to their higher stability and lower cytotoxicity, provided by their non-ionic surfactant and helper components. In this work, a three-formulation screening is performed, in terms of physicochemical and biological behavior, in CF patient derived airway epithelial cells. The most efficient niosome formulation reaches 28% of EGFP expressing live cells and follows caveolae-mediated endocytosis. Transfection with therapeutic cystic fibrosis transmembrane conductance regulator (CFTR) gene results in 5-fold increase of CFTR protein expression in transfected versus non-transfected cells, which leads to 1.5-fold increment of the chloride channel functionality. These findings highlight the relevance of niosome-based systems as an encouraging non-viral gene therapy platform with potential therapeutic benefits for CF.


Subject(s)
Chloride Channels , Cystic Fibrosis , Genetic Therapy , Chloride Channels/genetics , Cystic Fibrosis/genetics , Cystic Fibrosis/therapy , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Epithelial Cells , Humans , Respiratory System
16.
Pharmaceutics ; 12(5)2020 May 06.
Article in English | MEDLINE | ID: mdl-32384817

ABSTRACT

Oxidative damage has been linked to a number of diseases. Oleuropein (OLE), a natural occurring polyphenol from olive leaves (Olea europaea L.), is known to be a potent antioxidant compound with inherent instability and compromised bioavailability. Therefore, in this work, nanostructured lipid carriers (NLCs) were proposed for OLE encapsulation to protect and improve its antioxidant efficacy. The lipid matrix, composed of olive oil and Precirol, was optimized prior to OLE encapsulation. The characterization of the optimized oleuropein-loaded NLCs (NLC-OLE) showed a mean size of 150 nm, a zeta potential of -21 mV, an encapsulation efficiency of 99.12%, sustained release profile, and improved radical scavenging activity. The cellular in vitro assays demonstrated the biocompatibility of the NLCs, which were found to improve and maintain OLE antioxidant efficacy in the A549 and CuFi-1 lung epithelial cell lines, respectively. Overall, these findings suggest a promising potential of NLC-OLE to further design a pulmonary formulation for OLE delivery in lung epithelia.

17.
Mol Pharm ; 17(6): 1848-1858, 2020 06 01.
Article in English | MEDLINE | ID: mdl-32293897

ABSTRACT

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.


Subject(s)
Central Nervous System Diseases/therapy , Central Nervous System/pathology , Genetic Therapy/methods , Animals , Brain/metabolism , Brain/pathology , Cell Survival/physiology , Cells, Cultured , Central Nervous System/metabolism , Central Nervous System Diseases/metabolism , Female , Mice , Pregnancy , Rats , Rats, Sprague-Dawley , Vascular Endothelial Growth Factor A/metabolism
18.
Pharmaceutics ; 12(3)2020 Feb 25.
Article in English | MEDLINE | ID: mdl-32106545

ABSTRACT

Non-viral vectors have emerged as a promising alternative to viral gene delivery systems due to their safer profile. Among non-viral vectors, recently, niosomes have shown favorable properties for gene delivery, including low toxicity, high stability, and easy production. The three main components of niosome formulations include a cationic lipid that is responsible for the electrostatic interactions with the negatively charged genetic material, a non-ionic surfactant that enhances the long-term stability of the niosome, and a helper component that can be added to improve its physicochemical properties and biological performance. This review is aimed at providing recent information about niosome-based non-viral vectors for gene delivery purposes. Specially, we will discuss the composition, preparation methods, physicochemical properties, and biological evaluation of niosomes and corresponding nioplexes that result from the addition of the genetic material onto their cationic surface. Next, we will focus on the in situ application of such niosomes to deliver the genetic material into immune-privileged tissues such as the brain cortex and the retina. Finally, as future perspectives, non-invasive administration routes and different targeting strategies will be discussed.

19.
Nanomedicine ; 17: 308-318, 2019 04.
Article in English | MEDLINE | ID: mdl-30790710

ABSTRACT

Low transfection efficiency is a major challenge to overcome in non-viral approaches to reach clinical practice. Our aim was to explore new strategies to achieve more efficient non-viral gene therapies for clinical applications and in particular, for retinal diseases. Cationic niosomes and three GFP-encoding genetic materials consisting on minicircle (2.3 kb), its parental plasmid (3.5 kb) and a larger plasmid (5.5 kb) were combined to form nioplexes. Once fully physicochemically characterized, in vitro experiments in ARPE-19 retina epithelial cells showed that transfection efficiency of minicircle nioplexes doubled that of plasmids ones, maintaining good cell viability in all cases. Transfections in retinal primary cells and injections of nioplexes in rat retinas confirmed the higher capacity of cationic niosomes vectoring minicircle to deliver the genetic material into retina cells. Therefore, nioplexes based on cationic niosomes vectoring minicircle DNA represent a potential tool for the treatment of inherited retinal diseases.


Subject(s)
Genetic Vectors/administration & dosage , Liposomes/chemistry , Retinal Diseases/therapy , Transfection/methods , Animals , Cations/chemistry , Cell Line , Cells, Cultured , Genetic Therapy/methods , Genetic Vectors/genetics , Genetic Vectors/therapeutic use , Humans , Lipids/chemistry , Male , Quaternary Ammonium Compounds/chemistry , Rats, Sprague-Dawley , Retina/cytology , Retina/metabolism , Retinal Diseases/genetics , Squalene/chemistry
20.
Int J Pharm ; 550(1-2): 388-397, 2018 Oct 25.
Article in English | MEDLINE | ID: mdl-30009984

ABSTRACT

The success of non-viral vectors based on cationic niosomes for retinal gene delivery applications depends on the ability to achieve persistent and high levels of transgene expression, ideally from a single administration. In this work, we studied the effect of the non-ionic surfactant component of niosomes in their transfection efficiency in rat retina. For that purpose, three niosome formulations that only differed in the non-ionic tensioactives were elaborated. Niosomes contained: cationic lipid 1,2-di-O-octadecenyl-3-trimethylammonium propane (DOTMA), helper lipid squalene and polysorbate 20, polysorbate 80 or polysorbate 85. Niosomes and corresponding nioplexes were fully characterized in terms of size, polydispersity index, zeta potential, morphology and ability to protect and release DNA. In vitro experiments were carried out to evaluate transfection efficiency, cell viability and intracellular trafficking pathways of the formulations. Nioplexes based on polysorbate 20 niosomes were the most efficient transfecting retinal cells in vitro. Moreover, subretinal and intravitreal administration of those nioplexes in vivo showed also high levels of transgene expression in rat retinas. Our results demonstrate that the incorporation of polysorbate 20 in cationic niosomes enhances retinal gene delivery. Thus, this formulation emerges as a potential non-viral candidate to efficiently transfer specific therapeutic genes into the eye for biomedical purposes.


Subject(s)
Gene Transfer Techniques , Green Fluorescent Proteins/genetics , Polysorbates/administration & dosage , Retina/metabolism , Surface-Active Agents/administration & dosage , Animals , Cell Line , Humans , Injections, Intraocular , Liposomes , Male , Plasmids , Rats, Sprague-Dawley
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