Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA

Olbrich, Carsten; Bakowsky, Udo; Lehr, Claus‐Michael; Müller, Rainer H.; Kneuer, Carsten

doi:10.1016/s0168-3659(01)00506-5

Cited by 167 publications

(76 citation statements)

References 24 publications

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“…As a carrier system, solid lipid nanoparticles have many features that are valuable for nanomedicine. So far, SLNs have been investigated as delivery systems mostly for drugs and rarely for genes (14)(15)(16)(18)(19)(20). In both cases, this delivery system is reported to proceed more efficiently compared to the drug or gene alone.…”

Section: Percent Of Cells Expressed Gfpmentioning

confidence: 99%

Cationic Solid Lipid Nanoparticles Loaded by Cystein Proteinase Genes as a Novel anti-Leishmaniasis DNA Vaccine Delivery System: Characterization and in vitro Evaluations

et al. 2010

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-Purpose. Leishmaniasis is a major health problem in many tropical and sub-tropical countries and development of a safe and easily-available vaccine has high priority. Although several antigens potentially capable of inducing protective immunity have been studied, in the absence of pharmaceutical industry interest they have remained as fine publications only. Amongst them, Cathepsin L-like cysteine proteinases (CPs) have received considerable attention and type I and II CPs have been used in a heterologous prime-boost vaccination regime for experimental visceral leishmaniasis in dogs. Due to the promising results of the mentioned vaccination regime, we aimed to evaluate cationic solid lipid nanoparticles (cSLNs) for in vitro delivery of cpa, cpb and cpb CTE intended to be used as a cocktail DNA vaccine in our forthcoming studies. Methods: cSLNs were formulated of cetyl palmitate, cholesterol, DOTAP and Tween 80 via melt emulsification method followed by high shear homogenization. Different formulations were prepared by anchoring pDNAs on the surface of cSLNs via charge interaction. The formulations were characterized according to their size and zeta potential as well as pDNA integrity and stability against DNase I treatment. Lipoplexes' cytotoxicity was investigated on COS-7 cells by MTT test. The effect of the DOTAP:pDNA ratio on protection ability and cytotoxicity was also studied. In vitro transfection efficiency was qualified by florescent microscopy and quantified using flow cytometry technique. Results: cSLN-pDNA complexes were formulated with suitable size and zeta potential. Efficiency/cytotoxicity ratio of cSLN-pDNAs formulations was comparable to linear PEI-25kDa-pDNAs polyplexes while exhibiting significantly lower cytotoxicity. Conclusion: Tested formulations were able to deliver immunogenic CP genes efficiently. This data proves the ability of this system as a promising DNA vaccine carrier for leishmaniasis to cover the main drawback of naked pDNA delivery that is rapidly elimination from the circulation.

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Section: Percent Of Cells Expressed Gfpmentioning

confidence: 99%

Cationic Solid Lipid Nanoparticles Loaded by Cystein Proteinase Genes as a Novel anti-Leishmaniasis DNA Vaccine Delivery System: Characterization and in vitro Evaluations

et al. 2010

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“…Outra técnica que tem sido empregada para caracterizar a morfologia de superfície das nanopartículas é a microscopia de força atômica [69][70][71][72] , a qual fornece informações com alta resolução em três dimensões, em escala nanométrica, sendo capaz ainda de resolver detalhes de superfície em nível atômico 72 . Feng e colaboradores 69 empregaram esta técnica visando um estudo morfológico mais detalhado de nanoesferas de PLGA, preparadas empregando-se diferentes emulsificantes.…”

Section: Avaliação Morfológicaunclassified

Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos

et al. 2003

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Recebido em 28/10/02; aceito em 27/2/03 PHYSICOCHEMICAL CHARACTERIZATION AND STABILITY OF THE POLYMERIC NANOPARTICLE SYSTEMS FOR DRUG ADMINISTRATION. Polymeric nanoparticle systems such as nanocapsules and nanospheres present potential applications for the administration of therapeutic molecules. The physico-chemical characteristics of nanoparticle suspensions are important pre-requisites of the success of any dosage form development. The purpose of this review is to present the state of the art regarding the physico-chemical characterization of these drug carriers, in terms of the particle size distribution, the morphology, the polymer molecular weight, the surface charge, the drug content and the in vitro drug release profiles. Part of the review is devoted to the description of the techniques to improve the stability of colloidal systems.Keywords: nanoparticles; polymers; characterization. INTRODUÇÃOO controle da liberação de fármacos em sítios de ação específi-cos, através da utilização de vetores, capazes de permitir a otimização da velocidade de cedência e do regime de dosagem das substâncias, tem sido uma área de intensa pesquisa nos últimos dez anos. Dentre os vetores, incluem-se as micropartículas e os sistemas coloidais (lipossomas e nanopartículas). As nanopartículas, constituídas por polímeros biodegradáveis, têm atraído maior atenção dos pesquisadores em relação aos lipossomas, devido às suas potencialidades terapêuticas, à maior estabilidade nos fluídos biológicos e durante o armazenamento 1-3 . As nanopartículas poliméricas são sistemas carreadores de fármacos que apresentam diâmetro inferior a 1 µm. O termo nanopartícula inclui as nanocápsulas e as nanoesferas, as quais diferem entre si segundo a composição e organização estrutural (Figura 1). As nanocápsulas são constituídas por um invólucro polimérico disposto ao redor de um núcleo oleoso, podendo o fármaco estar dissolvido neste núcleo e/ou adsorvido à parede polimérica. Por outro lado, as nanoesferas, que não apresentam óleo em sua composição, são formadas por uma matriz polimérica, onde o fármaco pode ficar retido ou adsorvido 2,4,5 . Estes sistemas têm sido desenvolvidos visando inúmeras aplicações terapêuticas, sendo planejados, principalmente, para administração parenteral, oral ou oftálmica. Uma das áreas mais promissoras na utilização das nanopartículas é a vetorização de fármacos anticancerígenos 2,6-8 e de antibióticos 2,9,10 , principalmente através de administração parenteral, almejando uma distribuição mais seletiva dos mesmos e, assim, um aumento do índice terapêutico. Com relação à administração oral de nanopartículas, as pesquisas têm sido direcionadas especialmente à: a) diminuição dos efeitos colaterais de certos fármacos, destacando-se os antiinflamatórios não-esteróides (diclofenaco 11,12 , indometacina 13-15 ), os quais causam freqüentemente irritação à mucosa gastrintestinal e b) proteção de fármacos degradáveis no trato gastrintestinal, como peptídeos 16,17 , proteínas 8,18 e/ou hormônios 19 , aumentando a biodisponi...

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“…For the latter, specific ligands grafted at the surface of the LNP promote the docking of the LNPs at the matching receptors of the target cells. 3,7 The DNA binding and in vitro transfection efficiency for cetyl palmitate cLNP, stabilized by TW, SP and DOTAP, and liposomes prepared from the same stabilizers, were found to be very similar. 8 In previous studies Compritol s ATO 888 (a mixture of mono-, di-and triglyerides of mainly behenic fatty acids), 3,7,[9][10][11] Precirol s ATO 5 (glycerol distearate), 12 cetyl palmitate 8,9 or fatty a Professur für Nanomaterialcharakterisierung (Streumethoden), Friedrich-Alexander-Universität Erlangen-Nürnberg, Staudtstr.…”

Section: Introductionmentioning

confidence: 92%

“…3,4 Viral vectors are associated with potential safety concerns. Furthermore, in contrast to non-viral vectors, the size of the transported macromolecules is rather limited.…”

Section: Introductionmentioning

confidence: 99%

“…E-mail: tobias.unruh@fau.de b German Engineering Materials Science Centre (GEMS) at Heinz Maier-Leibnitz acids like oleic and stearic acid were used as matrix lipids. Nonionic stabilizers like TW(+SP) and PLX and different cationic co-stabilizers like CPYC, 3,9 CTAB, 9 EQ1, 3,9 DODAB [9][10][11] and DOTAP 8,9,12 were used to stabilize the cLNP and to equip them with a positive charge.…”

Section: Introductionmentioning

confidence: 99%

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Analysis of the structure of nanocomposites of triglyceride platelets and DNA

Schmiele

Knittel

Unruh

et al. 2015

Phys. Chem. Chem. Phys.

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DNA-complexes with platelet-like, cationically modified lipid nanoparticles (cLNPs) are studied with regard to the formation of nanocomposite structures with a sandwich-like arrangement of the DNA and platelets. For this purpose suspensions of platelet-like triglyceride nanocrystals, stabilized by a mixture of two nonionic (lecithin plus polysorbate 80 or poloxamer 188) and one cationic stabilizer dimethyldioctadecylammonium (DODAB), are used. The structure of the platelets in the native suspensions and their DNA-complexes, ranging from the sub-nano to the micron scale, is investigated with small-and wideangle scattering (SAXS, SANS, WAXS), calorimetry, photon correlation spectroscopy, transmission electron microscopy and computer simulations. The appearance of strong, lamellarly ordered peaks in the SAXS patterns of the DNA-complexes suggests a stacked arrangement of the nanocrystals, with the DNA being partially condensed between the platelets. This finding is supported with computer simulated small-angle scattering patterns of nanocrystal stacks, which can reproduce the measured small-angle scattering patterns on an absolute scale. The influence of the choice of the nonionic stabilizers and the amount of the cationic stabilizer DODAB on the structure of the native suspensions and the inner structure of their DNA-complexes is studied, too. Using high amounts of DODAB, lecithins with saturated acyl chains and polysorbate 80 instead of poloxamer 188 produces thinner nanocrystals, and thus decreases their repeat distances in the nanocomposites. Such nanocomposites could be of interest as DNA carriers, where the triglyceride platelets protect the sandwiched DNA from degradation.

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Cationic solid-lipid nanoparticles can efficiently bind and transfect plasmid DNA

Cited by 167 publications

References 24 publications

Cationic Solid Lipid Nanoparticles Loaded by Cystein Proteinase Genes as a Novel anti-Leishmaniasis DNA Vaccine Delivery System: Characterization and in vitro Evaluations

Cationic Solid Lipid Nanoparticles Loaded by Cystein Proteinase Genes as a Novel anti-Leishmaniasis DNA Vaccine Delivery System: Characterization and in vitro Evaluations

Caracterização e estabilidade físico-química de sistemas poliméricos nanoparticulados para administração de fármacos

Analysis of the structure of nanocomposites of triglyceride platelets and DNA

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