Polymeric Nanoparticles Loaded with Acyclovir: Formulation, Characterization and In-Vitro Drug Prolonged-Release Study

Author(s): Tran Thi Hai Yen*, Nguyen Tran Linh, Vu Thi Thu Giang, Hoang Lan Anh

Journal Name: Current Nanomedicine
(Formerly Recent Patents on Nanomedicine)

Volume 10 , Issue 3 , 2020


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Graphical Abstract:


Abstract:

Objectives: Acyclovir (ACV) is an antiviral drug, which requires frequent dosing regimen because of poor oral bioavailability and short half-life. In this study, ACV nanoparticles were formulated using ammonium methacrylates copolymers such as Eudragit RS 100 (Eud RS) and Eudragit RL 100 (Eud RL) to prolong release drug, and increase bioavailability.

Methods: ACV loaded nanoparticles were prepared by the solvent replacement technique and then were characterized by particle size, distribution, entrapment efficiency, differential scanning calorimeter, transmission electron microscope, and in-vitro drug release.

Results: It was found that as drug:polymer ratio changed from 1:2 to1:5, particle size and drug entrapment efficiency increased significantly. ACV– Eud RS loaded nanoparticles had a larger mean diameter of 363 nm in comparison to 200 nm of ACV- Eud RL nanoparticles. DSC results showed that in the prepared ACV-Eud RS nanoparticles, the drug was presented in the amorphous phase and may have been molecularly dispersed in the polymer matrix, but in the ACV-Eud RL nanoparticles, the drug was presented in the particles and homogeneously dispersed in the polymeric matrix. The entrapment efficiency of AVC-Eud RS nanoparticles was higher than that of ACV-Eud RL nanoparticles. In vitro drug release study showed that the ratios of released drug from ACV-Eud RS nanoparticles in the range from 58±3.8 to 62.9±4.6%, which was lower than those from ACV-Eud RL nanoparticles, in the range from 73.3±4.9 to 77.9±2.9%. The release was found to follow the Weibull model with a Fickian diffusion mechanism for both ACVEud RS and ACV- Eud RL nanoparticles.

Conclusion: These results suggest that ACV nanoparticles based on Eud RS100 and Eud RL100 could prolong the release of the drug.

Keywords: Polymer nanoparticles, acyclovir, prolonged-release, nanoprecipitation, Eudragit RS 100, Eudragit RL 100.

[1]
Wagstaff AJ, Faulds D, Goa KL. Aciclovir. A reappraisal of its antiviral activity, pharmacokinetic properties and therapeutic efficacy. Drugs 1994; 47(1): 153-205.
[http://dx.doi.org/10.2165/00003495-199447010-00009] [PMID: 7510619]
[2]
de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. The J Antimicrob Chemother 1983; 12(Suppl. B): 29-37.
[http://dx.doi.org/10.1093/jac/12.suppl_B.29]
[3]
Vergin H, Kikuta C, Mascher H, Metz R. Pharmacokinetics and bioavailability of different formulations of aciclovir. Arzneimittelforschung 1995; 45(4): 508-15.
[PMID: 7779152]
[4]
Bhosale U, Kusum DV, Jain N. Formulation and optimization of mucoadhesive nanodrug delivery system of acyclovir. J Young Pharm 2011; 3(4): 275-83.
[http://dx.doi.org/10.4103/0975-1483.90236] [PMID: 22224033]
[5]
Kyada C, Ranch K, Shah D. Optimization of mucoadhesive microspheres of acyclovir by applying 32 full factorial design. J Drug Deliv Sci Technol 2014; 24: 61-8.
[http://dx.doi.org/10.1016/S1773-2247(14)50009-3]
[6]
Attali P, Costantini D. Caroline Lemarchand. Mucoadhesive buccal tablets for the treatment of orofacial herpes 2009.https://patents.google.com/patent/ US859 2434 [April 11, 2018].
[7]
Vinodbhai PK, Gohel DMC. DRKP R, et al Sustained release floating microspheres of acyclovir: formulation, optimization, characterization and in vitro evaluation. Inter J Drug Dev Res 2009.
[8]
Gandhi A, Jana S, Sen KK. In-vitro release of acyclovir loaded Eudragit RLPO(®) nanoparticles for sustained drug delivery. Int J Biol Macromol 2014; 67: 478-82.
[http://dx.doi.org/10.1016/j.ijbiomac.2014.04.019] [PMID: 24755259]
[9]
Naderkhani E, Erber A, Škalko-Basnet N, Flaten GE. Improved permeability of acyclovir: optimization of mucoadhesive liposomes using the phospholipid vesicle-based permeation assay. J Pharm Sci 2014; 103(2): 661-8.
[http://dx.doi.org/10.1002/jps.23845] [PMID: 24395733]
[10]
Mukherjee B, Patra B, Layek B, Mukherjee A. Sustained release of acyclovir from nano-liposomes and nano-niosomes: an in vitro study. Int J Nanomedicine 2007; 2(2): 213-25.
[PMID: 17722549]
[11]
Devarajan PV, Sonavane GS. Preparation and in vitro/in vivo evaluation of gliclazide loaded Eudragit nanoparticles as a sustained release carriers. Drug Dev Ind Pharm 2007; 33(2): 101-11.
[http://dx.doi.org/10.1080/03639040601096695] [PMID: 17454041]
[12]
Tang J, Xu N, Ji H, Liu H, Wang Z, Wu L. Eudragit nanoparticles containing genistein: formulation, development, and bioavailability assessment. Int J Nanomedicine 2011; 6: 2429-35.
[PMID: 22072878]
[13]
Hoobakht F, Ganji F, Vasheghani-Farahani E, Mousavi SM. Eudragit RS PO nanoparticles for sustained release of pyridostigmine bromide. J Nanopart Res 2013; 15: 1912.
[http://dx.doi.org/10.1007/s11051-013-1912-y]
[14]
Yamaoka K, Nakagawa T, Uno T. Application of Akaike’s information criterion (AIC) in the evaluation of linear pharmacokinetic equations. J Pharmacokinet Biopharm 1978; 6(2): 165-75.
[http://dx.doi.org/10.1007/BF01117450] [PMID: 671222]
[15]
Kamel AO, Awad GAS, Geneidi AS, Mortada ND. Preparation of intravenous stealthy acyclovir nanoparticles with increased mean residence time. AAPS PharmSciTech 2009; 10(4): 1427-36.
[http://dx.doi.org/10.1208/s12249-009-9342-y] [PMID: 19949904]
[16]
Saltzman WM, Fung LK. Polymeric implants for cancer chemotherapy. Adv Drug Deliv Rev 1997; 26(2-3): 209-30.
[http://dx.doi.org/10.1016/S0169-409X(97)00036-7] [PMID: 10837544]
[17]
Siepmann J, Siepmann F. Mathematical modeling of drug delivery. Int J Pharm 2008; 364(2): 328-43.
[http://dx.doi.org/10.1016/j.ijpharm.2008.09.004] [PMID: 18822362]
[18]
Fu Y, Kao WJ. Drug release kinetics and transport mechanisms of non-degradable and degradable polymeric delivery systems. Expert Opin Drug Deliv 2010; 7(4): 429-44.
[http://dx.doi.org/10.1517/17425241003602259] [PMID: 20331353]
[19]
Papadopoulou V, Kosmidis K, Vlachou M, Macheras P. On the use of the Weibull function for the discernment of drug release mechanisms. Int J Pharm 2006; 309(1-2): 44-50.
[http://dx.doi.org/10.1016/j.ijpharm.2005.10.044] [PMID: 16376033]
[20]
Cardinal JR. Drug release from matrix devices recent advances in drug delivery systems. Boston, MA: Springer US 1984; pp. 229-48.
[http://dx.doi.org/10.1007/978-1-4613-2745-5_16]
[21]
Joshi AS, Patil CC, Shiralashetti SS, Kalyane NV. Design, characterization and evaluation of Eudragit microspheres containing glipizide. Drug Invention Today 2013; 5: 229-34.
[http://dx.doi.org/10.1016/j.dit.2013.06.009]


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Article Details

VOLUME: 10
ISSUE: 3
Year: 2020
Page: [271 - 279]
Pages: 9
DOI: 10.2174/2468187310999200701215154
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