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Physicochemical Characteristics, Cytotoxicity, and Antioxidant Activity of Three Lipid Nanoparticulate Formulations of Alpha-lipoic Acid

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Abstract

Exogenously supplied alpha-lipoic acid (LA) has proven to be effective as an antioxidant. In an effort to develop a water-soluble formulation for topical administration, LA was formulated in the form of solid lipid nanoparticles (SLN), nanostructure lipid carriers (NLC), and nanoemulsion (NE) and characterized in terms of physical and biological properties. Mean particle size of 113, 110, and 121 nm were obtained for NE, NLC, and SLN, respectively, with narrow size distribution. Zeta potential was approximately in the range of −25 to −40 mV. Disc and spherical structures of nanoparticles were observed by cryo-scanning electron microscopy. Entrapment efficiency of LA in three formulations was found to be more than 70%. After 120 days of storage at 25°C, physical stability of all formulations remained unchanged whereas the entrapment efficiency of SLN and NLC could be maintained, suggesting relative long-term stability. Prolonged release of LA formulation following the Higuchi model was found where a faster release was observed from NE compared with that of SLN and NLC. More than 80% of cell survivals were found up to 1 μM of LA concentrations. Antioxidant activity analysis demonstrated that all LA-loaded formulations expressed antioxidant activity at a similar magnitude as pure LA. These results suggest that chosen compositions of lipid nanoparticles play an important role on drug loading, stability, and biological activity of nanoparticles. Both SLN and NLC demonstrated their potential as alternative carriers for aqueous topical administration of LA.

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Abbreviations

DHLA:

dihydrolipoic acid

LA:

alpha-lipoic acid

NE:

nanoemulsion

NLC:

nanostructure lipid carriers

SLN:

solid lipid nanoparticles

ROS:

reactive oxygen species

Z :

ave particle diameter

MW:

molecular weight

PDI:

polydispersity index

ZP:

zeta potential

PCS:

photon correlation spectroscopy

SEM:

scanning electron microscopy

TEM:

transmission electron microscope

DSC:

differential scanning calorimetry

ΔH :

melting enthalpy

RI:

recrystallization index

HPLC:

high-performance liquid chromatography

EE:

entrapment efficiency

FBS:

fetal bovine serum

NHF:

human foreskin fibroblast

DMEM:

Dulbecco’s modified Eagle’s medium

MTT:

3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

PBS:

phosphate buffer saline

SD:

standard deviation

p value:

probability value

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Acknowledgements

This research was financially supported by the National Nanotechnology Center (NANOTEC), Thailand (research grant number B22 CR0102).

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Authors and Affiliations

  1. National Nanotechnology Center, National Science and Technology Development Agency, 111 Thailand Science Park, Paholyothin Road., Klong 1, Klong Luang, Pathumthani, 12120, Thailand

    Uracha Ruktanonchai, Piyawan Bejrapha & Usawadee Sakulkhu

  2. Faculty of Pharmacy, Silpakorn Univerity, Nakhonpathom, Thailand

    Praneet Opanasopit

  3. Department of Pharmacognosy, Faculty of Pharmacy, Mahidol University, Sri-ayudhya Road, Bangkok, 10400, Thailand

    Nuntavan Bunyapraphatsara, Varaporn Junyaprasert & Satit Puttipipatkhachorn

  4. Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Sri-ayudhya Road, Bangkok, 10400, Thailand

    Nuntavan Bunyapraphatsara, Varaporn Junyaprasert & Satit Puttipipatkhachorn

  5. Department of Manufacturing Pharmacy, Faculty of Pharmacy, Mahidol University, Sri-ayudhya Road, Bangkok, 10400, Thailand

    Nuntavan Bunyapraphatsara, Varaporn Junyaprasert & Satit Puttipipatkhachorn

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  1. Uracha Ruktanonchai
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Correspondence to Uracha Ruktanonchai.

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Ruktanonchai, U., Bejrapha, P., Sakulkhu, U. et al. Physicochemical Characteristics, Cytotoxicity, and Antioxidant Activity of Three Lipid Nanoparticulate Formulations of Alpha-lipoic Acid. AAPS PharmSciTech 10, 227–234 (2009). https://doi.org/10.1208/s12249-009-9193-6

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