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Effect of Solid Lipid Nanoparticles Formulation Compositions on Their Size, Zeta Potential and Potential for In Vitro pHIS-HIV-Hugag Transfection

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Abstract

Purpose

This work was conducted to determine model equations describing the effect of solid lipid nanoparticles (SLN) formulation compositions on their size and zeta potential using the face-centered central composite design and to determine the effect of SLN formulation compositions on the potential for in vitro pHIS-HIV-hugag transfection.

Materials and Methods

SLN were prepared by the hot high pressure homogenization technique using cetylpalmitate as lipid matrix at varying concentrations of Tween 80 and Span 85 mixture, dimethyldioctadecyl ammonium bromide (DDAB) and cholesterol. Size and zeta potential used as responses of the design were measured at pH 7.0. The model equations were accepted as statistical significance at p value of less than 0.05. Ability of SLN to form complex with pHIS-HIV-hugag was evaluated by electrophoretic mobility shift assay. In vitro cytotoxicity of SLN was studied in HeLa cells using alamar blue bioassay. The potential of SLN for in vitro pHIS-HIV-hugag transfection was also determined in HeLa cells by western blot technique.

Results

SLN possessed diameter in a range of 136–191 nm and zeta potential 11–61 mV depending on the concentrations of surfactant mixture, DDAB and cholesterol. The regression analysis showed that the model equations of responses fitted well with quadratic equations. The ability of SLN to form complex with pHIS-HIV-hugag was also affected by formulation compositions. In vitro cytotoxicity results demonstrated that HeLa cells were not well tolerant of high concentrations of SLN but still survived in a range of 100–200 μg/ml of SLN in culture medium. The results of transfection study showed ability of SLN to use as a vector for in vitro pHIS-HIV-hugag transfection. However, their potential for in vitro transfection was lower than the established transfection reagent.

Conclusions

Size and zeta potential of SLN could be predicted from their quadratic model equations achieved by combination of three variables surfactant, DDAB and cholesterol concentrations. In addition, these variables also affected the potential of SLN as a vector for in vitro pHIS-HIV-hugag transfection. The results here provide the framework for further study involving the SLN formulation design for DNA delivery.

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Abbreviations

Adj. R2 :

adjusted coefficient of determination

cm:

centimeter

CO2 :

carbon dioxide

CPC:

cetylpyridinium chloride

CTAB:

cetyltrimethylammonium bromide

°C:

degree Celsius

DDAB:

dimethyl dioctadecyl ammonium bromide

DMEM:

Dulbecco’s modified eagle’s medium

DOTAP:

N-[1-(2,3-dioleoyloxy)propyl]-N,N,N-trimethylammonium chloride

EDTA:

ethylenediaminetetraacetic acid

EQ1:

esterquat 1 (N,N-di-(B-stearoylethyl)-N,N-dimethyl-ammonium chloride

FBS:

fetal bovine serum

g:

gram

HAART:

highly active antiretroviral therapy

HIV:

human immunodeficiency virus

ml:

milliliter

mV:

millivolt

nm:

nanometer

PBS:

phosphate buffer saline

PCS:

photon correlation spectroscopy

pDNA:

plasmid deoxy ribonucleic acid

PI:

polydispersity index

psi:

pound per square inch

rpm:

round per minute

SD:

standard deviation

SLN:

solid lipid nanoparticles

TAE:

tris-acetate EDTA

TEM:

transmission electron microscopy

UV:

ultraviolet

v/v:

volume by volume

w/v:

weight by volume

w/w:

weight by weight

μg:

microgram

μl:

microliter

%:

percent

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Acknowledgments

The authors gratefully acknowledge the support for this work by the Thailand Research Fund (TRF) under the Royal Golden Jubilee PhD program grant and the Rachadapisek Sompoch Fund, Graduate School, Chulalongkorn University for providing Chulalongkorn University 90th Anniversary grant.

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Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Rathapon Asasutjarit & Garnpimol C. Ritthidej

  2. Faculty of Medicine, Chulalongkorn University, Bangkok, 10330, Thailand

    Sven-Iver Lorenzen, Sunee Sirivichayakul &  Kiat Ruxrungtham

  3. National Nanotechnology Center, National Science and Technology Development Agency (NSTDA), Thailand Science Park, Pathumthani, 12120, Thailand

    Uracha Ruktanonchai

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  1. Rathapon Asasutjarit
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  2. Sven-Iver Lorenzen
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Correspondence to Garnpimol C. Ritthidej.

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Asasutjarit, R., Lorenzen, SI., Sirivichayakul, S. et al. Effect of Solid Lipid Nanoparticles Formulation Compositions on Their Size, Zeta Potential and Potential for In Vitro pHIS-HIV-Hugag Transfection. Pharm Res 24, 1098–1107 (2007). https://doi.org/10.1007/s11095-007-9234-3

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  • DOI: https://doi.org/10.1007/s11095-007-9234-3

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