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

[ Vol. 7 , Issue. 5 ]

Author(s):

Ritika Kondel, Nusrat Shafiq*, Indu P. Kaur, Mini P. Singh, Avaneesh K. Pandey, Radha K. Ratho and Samir Malhotra   Pages 389 - 403 ( 15 )

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.

Affiliation:

Department of Pharmacology, PGIMER, Chandigarh, 160012, Department of Pharmacology, PGIMER, Chandigarh, 160012, UIPS, Punjab University, Chandigarh, 160014, Department of Virology, PGIMER, Chandigarh, 160012, Department of Pharmacology, PGIMER, Chandigarh, 160012, Department of Virology, PGIMER, Chandigarh, 160012, Department of Pharmacology, PGIMER, Chandigarh, 160012

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