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Dual Drug Delivery Using Lactic Acid Conjugated SLN for Effective Management of Neurocysticercosis

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Abstract

Purpose

The debut study was aimed to develop Lactic acid (LA)-conjugated solid lipid nanoparticles (SLN-LA) bearing albendazole (ALB) and prednisolone (PRD) for effective management of neurocysticercosis (NCC).

Methods

LA was coupled to SLN by post-insertion technique. SLNs were characterized for particle size and size distribution, shape, and percent drug entrapment efficiency. In vitro drug release kinetics, fluorescence study and in vitro transendothelial transport, hematological studies and pharmacokinetic studies were carried out to predict the fullest drug delivery potential.

Results

Spherical SLNs (~100 nm) with good drug entrapments (~64 and ~78% for ALB and PRD, respectively) showed in vitro initial fast release (i.e., 20–40% drugs release in 4 h) followed by sustained release for more than 48 h. Fluorescence study and in vitro transendothelial transport depicted selective brain uptake of SLN-LA compared to SLN attributed to carrier mediated transport via monocarboxylic acid transporters (MCT – 1/2/3). Pharmacokinetic parameters such as AUC0-t and AUMC0-t and Cllast showed good drugs withholding capacity of SLNs. Organ distribution studies reflected high accumulation of drugs (ALB, 7.6 ± 0.31%; PRD, 5.21 ± 0.24%) in the brain after 24 h in case of SLN-LA as compared to plain drugs solution. SLN-LA in hematological studies revealed insignificant toxicity to blood cells.

Conclusions

The overall study paved the potential advances in brain targeting with synergistic acting drugs for effective management of NCC.

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Abbreviations

%EE:

Percent entrapment efficiency

ACs:

Astrocyte cells

ALB:

Albendazole

BBB:

Blood brain barrier

BCECs:

Brain capillary endothelial cells

BCRP:

Breast cancer resistance protein

CMT:

Carrier mediated transporters

DDW:

Double distilled water

EDC:

1-ethyl-3-(3-dimethylaminopropyl) carbodiimide

FITC:

Fluorescein isothiocyanate

Hb:

Hemoglobin

HSPC:

Hydrogenated soya phosphatidylcholine

LA:

DL-lactic acid

MCT:

Monocarboxylic acid transporters

MRP:

Multidrug resistance proteins

NCC:

Neurocysticercosis

OLA:

OH protected LA

P-gp:

P-glycoprotein

PRD:

Prednisolone

RBC:

Red blood corpuscles

SA:

Stearylamine

SD:

Standard deviation

SLN-LA:

Lactic acid conjugated SLN loaded with ALB-PRD

SLNs:

Solid lipid nanoparticles

Sulfo-NHS:

N-Hydroxysulfosuccinimide

WBC:

White blood corpuscles

XRD:

X-ray diffraction

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ACKNOWLEDGMENTS AND DISCLOSURES

Authors are thankful to Mino Pharma and Sain Medicaments (Hyderabad, India) and Synmedic Laboratories, Faridabad (Haryana, India) for providing gift samples of drugs. We wish to acknowledge the support of Lipoid (Ludwigshafen Am Rhein, Germany) for rendering gift samples of lipids. The authors are also thankful to AIIMS, New Delhi for carrying out TEM and SEM studies. Authors namely Mr. Ankit Jain and Ms. Pooja Hurkat are highly obliged to Council of Scientific and Industrial Research (New Delhi, India) for rendering Senior Research Fellowship (SRF). The authors declare no competing financial interest and they alone are responsible for the content and writing of the manuscript.

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Authors and Affiliations

  1. Pharmaceutics Research Projects Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Vishwavidyalaya, Sagar, (M.P.), 470 003, India

    Rekha Devi, Ankit Jain, Pooja Hurkat & Sanjay K. Jain

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  1. Rekha Devi
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  2. Ankit Jain
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  3. Pooja Hurkat
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  4. Sanjay K. Jain
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Correspondence to Sanjay K. Jain.

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Devi, R., Jain, A., Hurkat, P. et al. Dual Drug Delivery Using Lactic Acid Conjugated SLN for Effective Management of Neurocysticercosis. Pharm Res 32, 3137–3148 (2015). https://doi.org/10.1007/s11095-015-1677-3

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  • DOI: https://doi.org/10.1007/s11095-015-1677-3

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