Journal Home > Online First

Graphene oxide (GO) and mesoporous silica nanoparticle (MSN) have been documented as advanced nanocarriers for drug delivery due to their unique and versatile properties. The design of GO–MSN nanocomposite offers a large surface area, adjustable pore size, biocompatibility, and low cytotoxicity. The application of acyclovir (ACV) (BCS: III) is suffering from poor permeability, low bioavailability, etc. Hence, the use of GO–MSN nanocomposite for the delivery of ACV may overcome the limitations of ACV. Therefore, the present work aims to design the lipid-coated ACV-loaded GO–MSN (LC-ACV-GO–MSN) nanocomposites. In brief, the design of experiments (DoE, 32 response surface methodology) approach was preferred for the development of GO–MSN nanocomposite. The loading of ACV in nanocomposite was done passive loading whereas the coating of lipids was done using a modified thin film hydration technique. At last, different spectral characterizations were performed. The output demonstrated that the entrapment efficiency of ACV-MSN and ACV-GO–MSN was 51.13% and 71.86%, respectively. Afterward, the designed LC-ACV-GO–MSN and ACV-GO–MSN nanocomposite shows 93.40% and 80.74% in vitro drug release, respectively. In conclusion, the design of LC-ACV-GO–MSN nanocomposite using optimized GO–MSN followed lipid coating offers the modified release. Therefore, in the future, LC-ACV-GO–MSN nanocomposite can be used for the delivery of ACV and other drug molecules with a high payload and enhanced release profile. We hope the current proof of concept may provide advantages over existing methods and emphasize the significance of protocells in cargo delivery systems.


menu
Abstract
Full text
Outline
About this article

Design of Surface Modified Acyclovir-loaded Graphene Oxide–Mesoporous Silica Nanocomposite: Optimization and In Vitro Characterization

Show Author's information Ketan B. Patil1,2( )Jayvadan K. Patel3,4Hardik H. Goswami5Arjun S. Chaudhari3
Nootan Pharmacy College, Sankalchand Patel University, Visnagar 384315, Gujarat, India
Department of Pharmaceutics, H. R. Patel Institute of Pharmaceutical Education and Research, Shirpur 425405, MH, India
Aavis Pharmaceuticals, Hoschton, GA 30548, USA
Nootan Pharmacy College, Sankalchand Patel University, Visnagar 384315, Gujarat, India
Biostatistics and Research Decision Sciences and Health Economics and Decision Sciences, Merck & Co, North Wales, PA, USA

Abstract

Graphene oxide (GO) and mesoporous silica nanoparticle (MSN) have been documented as advanced nanocarriers for drug delivery due to their unique and versatile properties. The design of GO–MSN nanocomposite offers a large surface area, adjustable pore size, biocompatibility, and low cytotoxicity. The application of acyclovir (ACV) (BCS: III) is suffering from poor permeability, low bioavailability, etc. Hence, the use of GO–MSN nanocomposite for the delivery of ACV may overcome the limitations of ACV. Therefore, the present work aims to design the lipid-coated ACV-loaded GO–MSN (LC-ACV-GO–MSN) nanocomposites. In brief, the design of experiments (DoE, 32 response surface methodology) approach was preferred for the development of GO–MSN nanocomposite. The loading of ACV in nanocomposite was done passive loading whereas the coating of lipids was done using a modified thin film hydration technique. At last, different spectral characterizations were performed. The output demonstrated that the entrapment efficiency of ACV-MSN and ACV-GO–MSN was 51.13% and 71.86%, respectively. Afterward, the designed LC-ACV-GO–MSN and ACV-GO–MSN nanocomposite shows 93.40% and 80.74% in vitro drug release, respectively. In conclusion, the design of LC-ACV-GO–MSN nanocomposite using optimized GO–MSN followed lipid coating offers the modified release. Therefore, in the future, LC-ACV-GO–MSN nanocomposite can be used for the delivery of ACV and other drug molecules with a high payload and enhanced release profile. We hope the current proof of concept may provide advantages over existing methods and emphasize the significance of protocells in cargo delivery systems.

Keywords: graphene oxide (GO)–mesoporous silica nanoparticle (MSN), acyclovir (ACV), protocell, drug delivery system (DDS), Design of Experiments (DoE)

References(38)

[1]

A. Sharma. Liposomes in drug delivery: Progress and limitations. International Journal of Pharmaceutics, 1997, 154(2): 123−140. https://doi.org/10.1016/s0378-5173(97)00135-x

[2]

A.M. Caminade, C.O. Turrin. Dendrimers for drug delivery. Journal of Materials Chemistry B, 2014, 2(26): 4055−4066. https://doi.org/10.1039/c4tb00171k

[3]

T. Zavvar, M. Babaei, K. Abnous, et al. Synthesis of multimodal polymersomes for targeted drug delivery and MR/fluorescence imaging in metastatic breast cancer model. International Journal of Pharmaceutics, 2020, 578: 119091. https://doi.org/10.1016/j.ijpharm.2020.119091

[4]
Y. Qiu, K. Park, Environment-sensitive hydrogels for drug delivery. Advanced Drug Delivery Reviews, 2001, 53(3): 321–339.
DOI
[5]

S. Croy, G. Kwon. Polymeric micelles for drug delivery. Current Pharmaceutical Design, 2006, 12(36): 4669−4684. https://doi.org/10.2174/138161206779026245

[6]

C. Mayer. Nanocapsules as drug delivery systems. The International Journal of Artificial Organs, 2005, 28(11): 1163−1171. https://doi.org/10.1177/039139880502801114

[7]

P.B. Han, C.W. Lin, K.J. Wang, et al. Aggregation-induced emission luminogen with excellent triplet–triplet upconversion efficiency for highly efficient non-doped blue organic light-emitting diodes. Materials Horizons, 2022, 9(1): 376−382. https://doi.org/10.1039/d1mh01129d

[8]

P.Y. Xu, C.P. Fu, R.K. Kankala, et al. Supercritical carbon dioxide-assisted nanonization of dihydromyricetin for anticancer and bacterial biofilm inhibition efficacies. The Journal of Supercritical Fluids, 2020, 161: 104840. https://doi.org/10.1016/j.supflu.2020.104840

[9]

M. Akbari, M. Ali Ghasemzadeh, M. Fadaeian. Synthesis and application of ZIF-8 MOF incorporated in a TiO2@Chitosan nanocomposite as a strong nanocarrier for the drug delivery of acyclovir. ChemistrySelect, 2020, 5(46): 14564−14571. https://doi.org/10.1002/slct.202003213

[10]

P. Liu, G.L. Chen, J.C. Zhang. A review of liposomes as a drug delivery system: Current status of approved products, regulatory environments, and future perspectives. Molecules, 2022, 27(4): 1372. https://doi.org/10.3390/molecules27041372

[11]

A.A. Chis, C. Dobrea, C. Morgovan, et al. Applications and limitations of dendrimers in biomedicine. Molecules, 2020, 25(17): 3982. https://doi.org/10.3390/molecules25173982

[12]

J. Wang, B.X. Li, L. Qiu, et al. Dendrimer-based drug delivery systems: History, challenges, and latest developments. Journal of Biological Engineering, 2022, 16(1): 18. https://doi.org/10.1186/s13036-022-00298-5

[13]

T. Anajafi, S. Mallik. Polymersome-based drug-delivery strategies for cancer therapeutics. Therapeutic Delivery, 2015, 6(4): 521−534. https://doi.org/10.4155/tde.14.125

[14]

T.R. Hoare, D.S. Kohane. Hydrogels in drug delivery: Progress and challenges. Polymer, 2008, 49(8): 1993−2007. https://doi.org/10.1016/j.polymer.2008.01.027

[15]

Y. Lu, E.S. Zhang, J.H. Yang, et al. Strategies to improve micelle stability for drug delivery. Nano Research, 2018, 11(10): 4985−4998. https://doi.org/10.1007/s12274-018-2152-3

[16]

P. Vega-Vásquez, N.S. Mosier, J. Irudayaraj. Nanoscale drug delivery systems: From medicine to agriculture. Frontiers in Bioengineering and Biotechnology, 2020, 8: 79. https://doi.org/10.3389/fbioe.2020.00079

[17]

K.X. Gu, F.Z. Meng. Former research and recent advances of metal-organic frameworks (MOF) for anti-cancer drug delivery. Journal of Physics:Conference Series, 2021, 2021(1): 012021. https://doi.org/10.1088/1742-6596/2021/1/012021

[18]

M. Esfahanian, M. Ali Ghasemzadeh, S.M.H. Razavian. Synthesis, identification and application of the novel metal-organic framework Fe3O4 @PAA@ZIF-8 for the drug delivery of ciprofloxacin and investigation of antibacterial activity. Artificial Cells,Nanomedicine,and Biotechnology, 2019, 47(1): 2024−2030. https://doi.org/10.1080/21691401.2019.1617729

[19]

R. Rahmatolahzadeh, M. Hamadanian, L. Ma’mani, et al. Aspartic acid functionalized PEGylated MSN@GO hybrid as an effective and sustainable nano-system for in-vitro drug delivery. Advances in Medical Sciences, 2018, 63(2): 257−264. https://doi.org/10.1016/j.advms.2018.01.003

[20]

A.T. Smith, A.M. La Chance, S.S. Zeng, et al. Synthesis, properties, and applications of graphene oxide/reduced graphene oxide and their nanocomposites. Nano Materials Science, 2019, 1(1): 31−47. https://doi.org/10.1016/j.nanoms.2019.02.004

[21]

M. Aliabadi, H. Shagholani, A. Yunessnia lehi. Synthesis of a novel biocompatible nanocomposite of graphene oxide and magnetic nanoparticles for drug delivery. International Journal of Biological Macromolecules, 2017, 98: 287−291. https://doi.org/10.1016/j.ijbiomac.2017.02.012

[22]

A.P. Subramanian, S.K. Jaganathan, E. Supriyanto. Overview on in vitro and in vivo investigations of nanocomposite based cancer diagnosis and therapeutics. RSC Advances, 2015, 5(89): 72638−72652. https://doi.org/10.1039/c5ra11912j

[23]

P.K. Deshmukh, S.H. Lakade, U.R. Jaiswal, et al. One step synthesis approach of mesoporous silica packed with graphene oxide nanosheet: Characterisation and drug release aspects. Materials Technology, 2022, 37(11): 1677−1690. https://doi.org/10.1080/10667857.2021.1972689

[24]

C.C. Zhang, H.Y. Xie, Z.Y. Zhang, et al. Applications and biocompatibility of mesoporous silica nanocarriers in the field of medicine. Frontiers in Pharmacology, 2022, 13: 829796. https://doi.org/10.3389/fphar.2022.829796

[25]

G. Bruni, M. Maietta, L. Maggi, et al. Preparation and physicochemical characterization of acyclovir cocrystals with improved dissolution properties. Journal of Pharmaceutical Sciences, 2013, 102(11): 4079−4086. https://doi.org/10.1002/jps.23721

[26]

J. Chen, B.W. Yao, C. Li, et al. An improved Hummers method for eco-friendly synthesis of graphene oxide. Carbon, 2013, 64: 225−229. https://doi.org/10.1016/j.carbon.2013.07.055

[27]

J.Q. Dalagan, E.P. Enriquez. One-step synthesis of mesoporous silica–graphene composites by simultaneous hydrothermal coupling and reduction of graphene oxide. Bulletin of Materials Science, 2014, 37(3): 589−595. https://doi.org/10.1007/s12034-014-0661-6

[28]

N. Han, Q.F. Zhao, L. Wan, et al. Hybrid lipid-capped mesoporous silica for stimuli-responsive drug release and overcoming multidrug resistance. ACS Applied Materials &Interfaces, 2015, 7(5): 3342−3351. https://doi.org/10.1021/am5082793

[29]

N.R. Shirsath, A.K. Goswami. Vildagliptin-loaded gellan gum mucoadhesive beads for sustained drug delivery: Design, optimisation and evaluation. Materials Technology, 2021, 36(11): 647−659. https://doi.org/10.1080/10667857.2020.1786783

[30]
R.J. Dias, K.K. Mali, V.S. Ghorpade, et al. In vitro absorption studies of acyclovir using natural permeation enhancers. Latin American Journal of Pharmacy, 2010, 29(8): 1411–1418.
[31]

E.Y. Choi, T.H. Han, J. Hong, et al. Noncovalent functionalization of graphene with end-functional polymers. Journal of Materials Chemistry, 2010, 20(10): 1907. https://doi.org/10.1039/b919074k

[32]
S. Kim, S. Philippot, S. Fontanay, et al. pH- and glutathione-responsive release of curcumin from mesoporous silica nanoparticles coated using tannic acid–Fe(iii) complex. RSC Advances, 2015, 5(110): 90550–90558.
DOI
[33]

L.D. Patil, U. Verma, U.D. Patil, et al. Inclusion of aceclofenac in mesoporous silica nanoparticles: Drug release study and statistical optimization of encapsulation efficiency by response surface methodology. Materials Technology, 2019, 34(12): 751−763. https://doi.org/10.1080/10667857.2019.1624301

[34]

M. Shamsipur, S.M. Pourmortazavi, A.A.M. Beigi, et al. Thermal stability and decomposition kinetic studies of acyclovir and zidovudine drug compounds. AAPS PharmSciTech, 2013, 14(1): 287−293. https://doi.org/10.1208/s12249-012-9916-y

[35]

V.V. Pande, K.S. Jadhav, M.A. Giri, et al. Design and development of paliperidone mesoporous silica template as a platform for surge dose drug delivery system. Materials Technology, 2019, 34(3): 117−125. https://doi.org/10.1080/10667857.2018.1538186

[36]

S.K. Maji, S. Sreejith, A.K. Mandal, et al. Immobilizing gold nanoparticles in mesoporous silica covered reduced graphene oxide: A hybrid material for cancer cell detection through hydrogen peroxide sensing. ACS Applied Materials &Interfaces, 2014, 6(16): 13648−13656. https://doi.org/10.1021/am503110s

[37]

L. Guardia, F. Suárez-García, J.I. Paredes, et al. Synthesis and characterization of graphene–mesoporous silica nanoparticle hybrids. Microporous and Mesoporous Materials, 2012, 160: 18−24. https://doi.org/10.1016/j.micromeso.2012.04.038

[38]

C. Ashok raja, S. Balakumar, B. Anandkumar, et al. Formation of bioactive nano hybrid thin films on anodized titanium via electrophoretic deposition intended for biomedical applications. Materials Today Communications, 2020, 25: 101666. https://doi.org/10.1016/j.mtcomm.2020.101666

Publication history
Copyright
Acknowledgements
Rights and permissions

Publication history

Received: 01 February 2024
Revised: 05 March 2024
Accepted: 21 March 2024
Published: 29 April 2024

Copyright

© The Author(s) 2024.

Acknowledgements

Acknowledgements

The researchers affiliated with the Faculty of Pharmacy, Nootan Pharmacy College, Sankalchand Patel University, Visnagar 384315, Gujarat, India, express their satisfaction, attributing it to the essential resources available that facilitate their research endeavors. The authors gratefully acknowledge HRPIPER Shipur for generously providing the necessary facilities that significantly contributed to their research activities.

Rights and permissions

This is an open-access article distributed under  the  terms  of  the  Creative  Commons  Attribution  4.0 International  License (CC BY) (http://creativecommons.org/licenses/by/4.0/), which  permits  unrestricted  use,  distribution,  and reproduction in any medium, provided the original author and source are credited.

Return