Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer

Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This st...

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Main Authors: Arul Prakash Francis, Aftab Ahmad, Sri Durga Devi Nagarajan, Harish Sundar Yogeeswarakannan, Krishnaraj Sekar, Shah Alam Khan, Dhanalekshmi Unnikrishnan Meenakshi, Asif Husain, Mohammed A. Bazuhair, Nandakumar Selvasudha
Format: Article
Language:English
Published: MDPI AG 2023-07-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/15/7/1919
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author Arul Prakash Francis
Aftab Ahmad
Sri Durga Devi Nagarajan
Harish Sundar Yogeeswarakannan
Krishnaraj Sekar
Shah Alam Khan
Dhanalekshmi Unnikrishnan Meenakshi
Asif Husain
Mohammed A. Bazuhair
Nandakumar Selvasudha
author_facet Arul Prakash Francis
Aftab Ahmad
Sri Durga Devi Nagarajan
Harish Sundar Yogeeswarakannan
Krishnaraj Sekar
Shah Alam Khan
Dhanalekshmi Unnikrishnan Meenakshi
Asif Husain
Mohammed A. Bazuhair
Nandakumar Selvasudha
author_sort Arul Prakash Francis
collection DOAJ
description Acyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC<sub>50</sub> of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy.
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spelling doaj.art-39781fa7f9854c5bae06ea8a220be8672023-11-18T20:55:40ZengMDPI AGPharmaceutics1999-49232023-07-01157191910.3390/pharmaceutics15071919Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin CancerArul Prakash Francis0Aftab Ahmad1Sri Durga Devi Nagarajan2Harish Sundar Yogeeswarakannan3Krishnaraj Sekar4Shah Alam Khan5Dhanalekshmi Unnikrishnan Meenakshi6Asif Husain7Mohammed A. Bazuhair8Nandakumar Selvasudha9Centre of Molecular Medicine and Diagnostics (COMMAND), Saveetha Dental College and Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600077, IndiaHealth Information Technology Department, The Applied College, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Pharmaceutical Technology, Anna University, Chennai 600025, IndiaDepartment of Pharmaceutical Technology, Anna University, Chennai 600025, IndiaDepartment of Pharmaceutical Technology, Anna University, Chennai 600025, IndiaCentre of Molecular Medicine and Diagnostics (COMMAND), Saveetha Dental College and Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600077, IndiaCentre of Molecular Medicine and Diagnostics (COMMAND), Saveetha Dental College and Hospitals, Saveetha Institute of Medical & Technical Sciences, Saveetha University, Chennai 600077, IndiaDepartment of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard, Hamdard Nagar, New Delhi 110062, IndiaDepartment of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi ArabiaDepartment of Biotechnology, Pondicherry University, Puducherry 605014, IndiaAcyclovir (ACV) is a promising candidate for drug repurposing because of its potential to provide an effective treatment for viral infections and non-viral diseases, such as cancer, for which limited treatment options exist. However, its poor physicochemical properties limit its application. This study aimed to formulate and evaluate an ACV-loaded red clay nanodrug delivery system exhibiting an effective cytotoxicity. The study focused on the preparation of a complex between ACV and red clay (RC) using sucrose stearate (SS) (nanocomplex F1) as an immediate-release drug-delivery system for melanoma treatment. The synthesized nanocomplex, which had nanosized dimensions, a negative zeta potential and the drug release of approximately 85% after 3 h, was found to be promising. Characterization techniques, including FT-IR, XRD and DSC-TGA, confirmed the effective encapsulation of ACV within the nanocomplex and its stability due to intercalation. Cytotoxicity experiments conducted on melanoma cancer cell lines SK-MEL-3 revealed that the ACV release from the nanocomplex formulation F1 effectively inhibited the growth of melanoma cancer cells, with an IC<sub>50</sub> of 25 ± 0.09 µg/mL. Additionally, ACV demonstrated a significant cytotoxicity at approximately 20 µg/mL in the melanoma cancer cell line, indicating its potential repurposing for skin cancer treatment. Based on these findings, it can be suggested that the RC-SS complex could be an effective drug delivery carrier for localized cancer therapy. Furthermore, the results of an in silico study suggested the addition of chitosan to the formulation for a more effective drug delivery. Energy and interaction analyses using various modules in a material studio demonstrated the high stability of the composite comprising red clay, sucrose stearate, chitosan and ACV. Thus, it could be concluded that the utilization of the red clay-based drug delivery system is a promising strategy to improve the effectiveness of targeted cancer therapy.https://www.mdpi.com/1999-4923/15/7/1919acyclovirred claydrug releasecytotoxicityin silico
spellingShingle Arul Prakash Francis
Aftab Ahmad
Sri Durga Devi Nagarajan
Harish Sundar Yogeeswarakannan
Krishnaraj Sekar
Shah Alam Khan
Dhanalekshmi Unnikrishnan Meenakshi
Asif Husain
Mohammed A. Bazuhair
Nandakumar Selvasudha
Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer
Pharmaceutics
acyclovir
red clay
drug release
cytotoxicity
in silico
title Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer
title_full Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer
title_fullStr Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer
title_full_unstemmed Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer
title_short Development of a Novel Red Clay-Based Drug Delivery Carrier to Improve the Therapeutic Efficacy of Acyclovir in the Treatment of Skin Cancer
title_sort development of a novel red clay based drug delivery carrier to improve the therapeutic efficacy of acyclovir in the treatment of skin cancer
topic acyclovir
red clay
drug release
cytotoxicity
in silico
url https://www.mdpi.com/1999-4923/15/7/1919
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