Login Register Cart 0
Generic placeholder image

Pharmaceutical Nanotechnology

Editor-in-Chief

ISSN (Print): 2211-7385
ISSN (Online): 2211-7393

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Effect of Acyclovir Solid Lipid Nanoparticles for the Treatment of Herpes Simplex Virus (HSV) Infection in an Animal Model of HSV-1 Infection

Author(s): Ritika Kondel, Nusrat Shafiq*, Indu P. Kaur, Mini P. Singh, Avaneesh K. Pandey, Radha K. Ratho and Samir Malhotra

Volume 7, Issue 5, 2019

Page: [389 - 403] Pages: 15

DOI: 10.2174/2211738507666190829161737

Abstract

Background: Acyclovir use is limited by a high frequency of administration of five times a day and low bioavailability. This leads to poor patient compliance.

Objectives: To overcome the problem of frequent dosing, we used nanotechnology platform to evaluate the proof of concept of substituting multiple daily doses of acyclovir with a single dose.

Methods: Acyclovir was formulated as solid lipid nanoparticles (SLN). The nanoparticles were characterized for particle size, surface charge and morphology and in vitro drug release. The pharmacokinetic and pharmacodynamic of SLN acyclovir were compared with conventional acyclovir in a mouse model.

Results: SLN showed drug loading of 90.22% with 67.44% encapsulation efficiency. Particle size was found to be of 131 ± 41.41 nm. In vitro drug release showed 100% release in SIF in 7 days. AUC0-∞ (119.43 ± 28.74 μg/ml h), AUMC0-∞ (14469 ± 4261.16 μg/ml h) and MRT (120.10 ± 9.21 h) were significantly higher for ACV SLN as compared to ACV AUC0-∞ (12.22 ± 2.47 μg/ml h), AUMC0-∞ (28.78 ± 30.16 μg/ml h) and MRT (2.07 ± 1.77 h), respectively (p<0.05). In mouse model, a single dose of ACV SLN was found to be equivalent to ACV administered as 400mg TID for 5 days in respect to lesion score and time of healing.

Conclusion: The proof of concept of sustained-release acyclovir enabling administration as a single dose was thus demonstrated.

Keywords: Acyclovir, HSV-1, pharmacodynamic, pharmacokinetic, Solid Lipid Nanoparticles (SLN), sustained release.

« Previous Next »
Graphical Abstract

[1]
Arvin A, Campadelli-Fiume G, Mocarski E, et al. Human herpesviruses: biology, therapy, and immunoprophylaxis. Cambridge University Press: Cambridge 2007.
[2]
Hay CM, Reichman RC. Antiviral drugs. In: Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ, Wolff K, Eds Fitzpatrick’s Dermatology in General Medicine. 7th ed. McGraw-Hill: New York 2008; pp. 2203-11.
[3]
Chang YC, Madkan VK, Sra K, Carrasco DA, Tyring SK. Systemic antiviral agents. In: Wolff K, Ed Comprehensive Dermatologic Drug Therapy. WB Saunders: Philadelphia 2007; pp. 101-24.
[4]
Dollery C. Therapeutic drugs. 2nd ed. Churchill Livingstone: Edinburgh 1999; pp. A39-44.
[5]
Goodman L, Gilman A, Brunton L, Lazo J, Parker K. Goodman & Gilman’s the pharmacological basis of therapeutics. 13th ed. McGraw-Hill: New York 2006; pp. 1106-7.
[6]
Arora A, Shafiq N, Jain S, Khuller GK, Sharma S, Malhotra S. Development of sustained release “NANOFDC (fixed dose combination)” for hypertension - an experimental study. PLoS One 2015; 10(6)e0128208
[7]
Arora A, Shafiq N, Jain S, et al. Development of sustained release “Nanopolypill” of ischemic heart disease drugs - an experimental study. Curr Nanosci 2014; 10(6): 816-26.
[8]
Kumar G, Malhotra S, Shafiq N, Pandhi P, Khuller GK, Sharma S. In vitro physicochemical characterization and short term in vivo tolerability study of ethionamide loaded PLGA nanoparticles: potentially effective agent for multidrug resistant tuberculosis. J Microencapsul 2011; 28(8): 717-28.
[9]
Kumar G, Sharma S, Shafiq N, Khuller GK, Malhotra S. Optimization, in vitro-in vivo evaluation, and short-term tolerability of novel levofloxacin-loaded PLGA nanoparticle formulation. J Pharm Sci 2012; 101(6): 2165-76.
[10]
de Jalón EG, Blanco-Príeto MJ, Ygartua P, Santoyo S. Increased efficacy of acyclovir-loaded microparticles against herpes simplex virus type 1 in cell culture. Eur J Pharm Biopharm 2003; 56(2): 183-7.
[11]
Müller RH, Mäder K, Gohla S. Solid lipid nanoparticles (SLN) for controlled drug delivery - a review of the state of the art. Eur J Pharm Biopharm 2000; 50(1): 161-77.
[12]
Yang S, Zhu J, Lu Y, Liang B, Yang C. Body distribution of camptothecin solid lipid nanoparticles after oral administration. Pharm Res 1999; 16(5): 751-7.
[13]
Demirel M, Yazan Y, Müller RH, Kiliç F, Bozan B. Formulation and in vitro-in vivo evaluation of piribedil solid lipid micro- and nanoparticles. J Microencapsul 2001; 18(3): 359-71.
[14]
Penkler L. MuÈller RH, Runge SA. Pharmaceutical cyclosporin formulation with improved biopharmaceutical properties, improved physical quality and greater stability, and method for producing said formulation United States Patent US 6551619B1 1999.
[15]
Abd-Rabou AA, Bharali DJ, Mousa SA. Taribavirin and 5-fluorouracil-loaded pegylated-lipid nanoparticle synthesis, p38 docking, and antiproliferative effects on MCF-7 breast cancer. Pharm Res 2018; 35(4): 76.
[16]
Jain AK, Jai SK. Galactosylated poly (d, l-lactic-co-glycolic acid) nanoparticles for liver targeted delivery of acyclovir. J Biomed Pharm Res 2013; 2: 7-14.
[17]
Bhalekar MR, Upadhaya PG, Madgulkar AR, Kshirsagar SJ, Dube A, Bartakke US. In vivo bioavailability and lymphatic uptake evaluation of lipid nanoparticulates of darunavir. Drug Deliv 2016; 23(7): 2581-6.
[18]
Cavalli R, Donalisio M, Bisazza A, et al. Enhanced antiviral activity of acyclovir loaded into nanoparticles. Methods Enzymol 2012; 509: 1-19.
[19]
Seyfoddin A, Al-Kassas R. Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Dev Ind Pharm 2013; 39(4): 508-19.
[20]
Bhandari R, Kaur IP. Pharmacokinetics, tissue distribution and relative bioavailability of isoniazid-solid lipid nanoparticles. Int J Pharm 2013; 441(1-2): 202-12.
[21]
Emami J, Bazargan N, Ajami A. HPLC determination of acyclovir in human serum and its application in bioavailability studies. Res Pharm Sci 2009; 4: 47-54.
[22]
Brown SD, White CA, Chu CK, Bartlett MG. Determination of acyclovir in maternal plasma, amniotic fluid, fetal and placental tissues by high-performance liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci 2002; 772(2): 327-34.
[23]
Lipipun V, Kurokawa M, Suttisri R, et al. Efficacy of Thai medicinal plant extracts against herpes simplex virus type 1 infection in vitro and in vivo. Antiviral Res 2003; 60(3): 175-80.
[24]
Docherty JJ, Smith JS, Fu MM, Stoner T, Booth T. Effect of topically applied resveratrol on cutaneous herpes simplex virus infections in hairless mice. Antiviral Res 2004; 61(1): 19-26.
[25]
Kurokawa M, Ochiai H, Nagasaka K, et al. Antiviral traditional medicines against herpes simplex virus (HSV-1), poliovirus, and measles virus in vitro and their therapeutic efficacies for HSV-1 infection in mice. Antiviral Res 1993; 22(2-3): 175-88.
[26]
Guidelines for the validation of analytical methods used in residue depletion studies www.ema.europa. eu/docs/en_GB/document...guideline/2010/.../WC500040499.pdf2010
[27]
Food Drug Administration. Zovirax®. Available at:. https://www.accessdata.fda.gov/drugsatfda_docs/label/2001/018604s018lbl.pdf
[28]
O’Brien JJ, Campoli-Richards DM. Acyclovir. An updated review of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1989; 37(3): 233-309.
[29]
Seyfoddin A, Al-Kassas R. Development of solid lipid nanoparticles and nanostructured lipid carriers for improving ocular delivery of acyclovir. Drug Dev Ind Pharm 2013; 39(4): 508-19.
[30]
Hasanovic A, Zehl M, Reznicek G, Valenta C. Chitosan-tripolyphosphate nanoparticles as a possible skin drug delivery system for aciclovir with enhanced stability. J Pharm Pharmacol 2009; 61(12): 1609-16.
[31]
Cortesi R, Ravani L, Menegatti E, Drechsler M, Esposito E. Colloidal dispersions for the delivery of acyclovir: a comparative study. Indian J Pharm Sci 2011; 73(6): 687-93.
[32]
Bhosale U, Kusum DV, Jain N. Formulation and optimization of mucoadhesive nanodrug delivery system of acyclovir. J Young Pharm 2011; 3(4): 275-83.
[33]
AK Jain, J. S. Galactosylated poly (d, l-lactic-co-glycolic acid) nanoparticles for liver targeted delivery of acyclovir. J Biomed Pharm Res 2013; 2: 7-1.
[34]
Rohit B, Pal KI. A method to prepare solid lipid nanoparticles with improved entrapment efficiency of hydrophilic drugs. Curr Nanosci 2013; 9: 29-33.
[35]
Aburahma MH, Badr-Eldin SM. Compritol 888 ATO: a multifunctional lipid excipient in drug delivery systems and nanopharmaceuticals. Expert Opin Drug Deliv 2014; 11(12): 1865-83.
[36]
Qi J, Lu Y, Wu W. Absorption, disposition and pharmacokinetics of solid lipid nanoparticles. Curr Drug Metab 2012; 13(4): 418-28.
[37]
Hu L, Tang X, Cui F. Solid lipid nanoparticles (SLNs) to improve oral bioavailability of poorly soluble drugs. J Pharm Pharmacol 2004; 56(12): 1527-35.
[38]
Italia JL, Yahya MM, Singh D, Ravi Kumar MNV. Biodegradable nanoparticles improve oral bioavailability of amphotericin B and show reduced nephrotoxicity compared to intravenous fungizone. Pharm Res 2009; 26(6): 1324-31.
[39]
Zhang Z, Lv H, Zhou J. Novel solid lipid nanoparticles as carriers for oral administration of insulin. Pharmazie 2009; 64(9): 574-8.
[40]
Müller RH, Runge S, Ravelli V, Mehnert W, Thünemann AF, Souto EB. Oral bioavailability of cyclosporine: solid lipid nanoparticles (SLN) versus drug nanocrystals. Int J Pharm 2006; 317(1): 82-9.
[41]
Zhuang CY, Li N, Wang M, et al. Preparation and characterization of vinpocetine loaded nanostructured lipid carriers (NLC) for improved oral bioavailability. Int J Pharm 2010; 394(1-2): 179-85.
[42]
Hariharan S, Bhardwaj V, Bala I, Sitterberg J, Bakowsky U, Ravi Kumar MNV. Design of estradiol loaded PLGA nanoparticulate formulations: a potential oral delivery system for hormone therapy. Pharm Res 2006; 23(1): 184-95.
[43]
Sharma CP, Kalarikkal N, Sandeep K, Thomas S, Pothen LA. Evaluation of in vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with aloe vera in glioma cells. Mater Sci Eng C 2016; 66: 40-50.
[44]
Baek JS, Cho CW. Surface modification of solid lipid nanoparticles for oral delivery of curcumin: improvement of bioavailability through enhanced cellular uptake, and lymphatic uptake. Eur J Pharm Biopharm 2017; 117: 132-40.
[45]
Mosallaei N, Jaafari MR, Hanafi-Bojd MY, Golmohammadzadeh S, Malaekeh-Nikouei B. Docetaxel-loaded solid lipid nanoparticles: preparation, characterization, in vitro, and in vivo evaluations. J Pharm Sci 2013; 102(6): 1994-2004.
[46]
Ahmadnia S, Moazeni M, Mohammadi-Samani S, Oryan A. In vivo evaluation of the efficacy of albendazole sulfoxide and albendazole sulfoxide loaded solid lipid nanoparticles against hydatid cyst. Exp Parasitol 2013; 135(2): 314-9.

Rights & Permissions Print Cite
Article Metrics
46
10
1
© 2024 Bentham Science Publishers | Privacy Policy