Lipid coated chitosan-DNA nanoparticles for enhanced gene delivery

Baghdan, Elias; Pinnapireddy, Shashank Reddy; Strehlow, Boris; Engelhardt, Konrad

doi:10.1016/j.ijpharm.2017.11.045

Cited by 96 publications

(53 citation statements)

References 41 publications

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“…After a series of lethal events, most of which were based on the use of viral vectors and because most immunogenic reactions or mutations were caused by viruses, gene therapy has experienced a strong suppression owing to safety concerns. However, significant advances have been made thanks to technological and scientific developments, and so non-viral delivery systems have been utilised in the transport of genetic materials over the years [20].…”

Section: Resultsmentioning

confidence: 99%

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In vitro preliminary studies of chitooligosaccharide coated nanostructered lipidic nanoparticles for efficient gene delivery

Şenel¹

2019

jrp

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How to cite this article: Şenel B. In vitro preliminary studies of chitooligosaccharide coated nanostructered lipidic nanoparticles for efficient gene delivery. J Res Pharm. 2019; 23(4): 671-681. ABSTRACT:Gene therapy is generally defined as the transfer of genetic material to cells to treat a disease or at least improve the clinical condition of a patient. The most commonly used vectors in gene therapy are viral and non-viral vectors. The aim of this study was to develop a gene carrier system based on chitooligosaccharide-coated nanostructured lipidic nanoparticles and evaluate the physicochemical properties, such as zeta potential, particle size, SEM images, pH, cytotoxicity, DNA-binding properties, serum stability and transfection to cells. In this study, cationic formulations were produced using Dynasan ® 116 and Transcutol ® P as a lipidic phase and chitooligosaccharide lactate for polymeric coating with DOTAP as a cationic agent. These formulations were made with the oil-in water hot emulsification technique. GFP was selected as the genetic material to be loaded into the formulations. According to the results, the chitooligosaccharide-coated cationic lipid nanoparticles prepared had considerably small particle sizes (144-178 nm) and high zeta potential (+37.6/+33.7mV). Based on the MTT assay, the cytotoxic effect of formulations on the NIH 3T3, A549 and MDA-MB-231 cell lines exhibited a dose-time-dependant pattern. Further, the prepared formulations binded DNA effectively and protected DNA against the serum component. It was concluded that chitooligosaccharide-coated lipidic nanoparticle formulations can be prepared as a pDNA-nanoparticle complex and can be employed as a gene delivery system effectively.

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Section: Resultsmentioning

confidence: 99%

“…The formulation of nanoparticle systems with a large surface area/volume ratio is hence very important. However, as size may affect cytotoxicity, optimum properties should be determined [20,34].…”

Section: Cell Viability and Transfectionmentioning

confidence: 99%

In vitro preliminary studies of chitooligosaccharide coated nanostructered lipidic nanoparticles for efficient gene delivery

Şenel¹

2019

jrp

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“…Other alternatives to liposomes-in-chitosan hydrogels have been also reported by entrapping liposomes (DPPC/Chol) and plasmid DNA into CSNPs. This strategy has enabled to protect CS from being deprotonated at physiological pH and thus overcoming important drawbacks associated to cytotoxicity and in vivo gene delivery (95,96).…”

Section: However It Is Well-known That Other Intermolecular Interactmentioning

confidence: 99%

Liposomes‐in‐Chitosan Hydrogels: Challenges and Opportunities for Biomedical Applications

Grijalvo

Eritja

Díaz

2019

Materials Science and Technology

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4 drug delivery (17) and tissue engineering (e.g. bone (18), cartilage (18,19) or neural (20) tissue regenerations). From the structural point of view, CS is a linear polysaccharide made of randomly distributed mixtures of deacetylated residues (β-(14)-linked-D-glucosamine) and acetylated residues (N-acetyl-Dglucosamine). This polysaccharide is commercially produced by deacetylation of chitin ( Figure 1A). The percentage of deacetylated and acetylated residues (so-called degree of deacetylation, DA) in CS determines its physicochemical properties as well as solubility (21), biodegradability and biological activity (22).The protonation of the amino groups on the CS backbone under acidic conditions permits the biopolymer solubility before reaching pH values that can range from 6.2 and 6.5. As a consequence, the amino groups of the Dgalactosamine units are predominantly positively charged at pH values below 6.2 (23, 24). The development of physical entanglements in CS hydrogels is governed by reversible non-covalent forces such as hydrogen, ionic and/or hydrophobic intermolecular interactions that depend on the pH, temperature, chemical composition and polymer chain length (24,25,26). Importantly, the robustness of CS-based hydrogels permits the incorporation of small molecules during the gelation process under mild conditions. In this regard, β-glycerophosphate (GP) has been described as an efficient catalyst to trigger the CS sol-to-gel transition at physiological pH. This process has led to transparent physically cross-linked hydrogels with potential use as injectable biomaterials (24) ( Figure 1B). Other small anionic molecules have also been described as effective ionic cross-linking agents including a) citrate and sulphates, b) transition metal ions like Pt (II) (27) or Mo (IV) (28), and c) the use

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“…Chitosan is safe and degradable as a non-viral gene vector, but the transfection efficiency is limited [1,2]. Modification of chitosan with arginine [3], histidine [4], lysine [4], Polyethylenimine [5], polyethylene glycol (PEG) [1], lipid [6], inorganic nanoparticles [7], and branched structure [8,9] can improve chitosan transfection to a certain degree, but the resulting materials are still not efficient enough or mass produced, which limits the wide range of applications.. PEGylated gene carriers generally achieve higher gene transfection efficiency [1,10,11]. PEG could promote transfection by another method.…”

Section: Introductionmentioning

confidence: 99%

Endosomal explosion induced by hypertonicity

Wang

2019

Preprint

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Transferring DNA into cells to regulate cell function is a novel research field in recent decades.Chitosan is a gene vector with the properties of low-cost and safe，but high efficient delivery has remained challenging. We developed a strategy termed EEIH，for endosomal explosion induced by hypertonicity, in which short-time exposure to hypertonic solutions triggers endosomes destabilization like explosions. EEIH can force chitosan/DNA polyplexes to break through the endosomal barriers to approach the nucleus, which results in boosting the transfection efficiency of chitosan in several cell lines. We demonstrate that EEIH is a significant and practical strategy in chitosan transfection system without sophisticated modification of chitosan.

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Lipid coated chitosan-DNA nanoparticles for enhanced gene delivery

Cited by 96 publications

References 41 publications

In vitro preliminary studies of chitooligosaccharide coated nanostructered lipidic nanoparticles for efficient gene delivery

In vitro preliminary studies of chitooligosaccharide coated nanostructered lipidic nanoparticles for efficient gene delivery

Liposomes‐in‐Chitosan Hydrogels: Challenges and Opportunities for Biomedical Applications

Endosomal explosion induced by hypertonicity

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