A β-Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer
β−sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β−sitosterol including lowering low-densit...
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| Published in | Pharmaceutics Vol. 14; no. 8; p. 1711 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Switzerland
MDPI AG
01.08.2022
MDPI |
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| Abstract | β−sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β−sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β−sitosterol encapsulated Alginate/Chitosan nanoparticles (β−sito−Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β−sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β−sito−Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β−sito−Alg/Ch/NPs as compared to β−sito−suspension. The β−sito−Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β−sito−Alg/Ch/NPs and β−sito−suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β−sito−Alg/Ch/NPs and β−sito−suspension. When compared to the β−sito−suspension, the β−sito−Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β−sito−Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β−sito−suspension. |
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| AbstractList | β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β–sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β–sitosterol encapsulated Alginate/Chitosan nanoparticles (β–sito–Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β–sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β–sito–Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β–sito–Alg/Ch/NPs as compared to β–sito–suspension. The β–sito–Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β–sito–Alg/Ch/NPs and β–sito–suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β–sito–Alg/Ch/NPs and β–sito–suspension. When compared to the β–sito–suspension, the β–sito–Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β–sito–Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β–sito–suspension. β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β–sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β–sitosterol encapsulated Alginate/Chitosan nanoparticles (β–sito–Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β–sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β–sito–Alg/Ch/NPs was also studied. The pharmacokinetic parameters including C[sub.max] , T[sub.max] , half-life (t[sub.1/2] ), and bioavailability were measured for β–sito–Alg/Ch/NPs as compared to β–sito–suspension. The β–sito–Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β–sito–Alg/Ch/NPs and β–sito–suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β–sito–Alg/Ch/NPs and β–sito–suspension. When compared to the β–sito–suspension, the β–sito–Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β–sito–Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β–sito–suspension. β−sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β−sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β−sitosterol encapsulated Alginate/Chitosan nanoparticles (β−sito−Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β−sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β−sito−Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β−sito−Alg/Ch/NPs as compared to β−sito−suspension. The β−sito−Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β−sito−Alg/Ch/NPs and β−sito−suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β−sito−Alg/Ch/NPs and β−sito−suspension. When compared to the β−sito−suspension, the β−sito−Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β−sito−Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β−sito−suspension. β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β–sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β–sitosterol encapsulated Alginate/Chitosan nanoparticles (β–sito–Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β–sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β–sito–Alg/Ch/NPs was also studied. The pharmacokinetic parameters including C max , T max , half-life (t 1/2 ), and bioavailability were measured for β–sito–Alg/Ch/NPs as compared to β–sito–suspension. The β–sito–Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β–sito–Alg/Ch/NPs and β–sito–suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β–sito–Alg/Ch/NPs and β–sito–suspension. When compared to the β–sito–suspension, the β–sito–Alg/Ch/NPs demonstrated greater cytotoxicity ( p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β–sito–Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β–sito–suspension. |
| Audience | Academic |
| Author | Akhter, Md Habban Zeyaullah, Mohammad Khalilullah, Habibullah Ali, Abuzer Jaremko, Mariusz Afzal, Obaid Dawria, Adam Altamimi, Abdulmalik S A Abdel Aziz Ibrahim, Ibrahim Shahzad, Naiyer Emwas, Abdul-Hamid Rahman, Mohammad Akhlaquer Muzammil, Khursheed Mir Najib Ullah, Shehla Nasar Ahmad, Irfan |
| AuthorAffiliation | 4 Department of Public Health, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha 62521, Saudi Arabia 9 Department of Pharmacognosy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia 7 Department of Pharmacognosy, Faculty of Pharmacy, King Khalid University, Abha 62521, Saudi Arabia 1 Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia 8 Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia 5 Department of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha 62521, Saudi Arabia 6 Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi Arabia 10 Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia 3 Dep |
| AuthorAffiliation_xml | – name: 7 Department of Pharmacognosy, Faculty of Pharmacy, King Khalid University, Abha 62521, Saudi Arabia – name: 3 Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 62521, Saudi Arabia – name: 9 Department of Pharmacognosy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia – name: 1 Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia – name: 4 Department of Public Health, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha 62521, Saudi Arabia – name: 5 Department of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha 62521, Saudi Arabia – name: 8 Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia – name: 11 Smart-Health Initiative (SHI) and Red Sea Research Center (RSRC), Division of Biological and Environmental Sciences and Engineering (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia – name: 12 Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia – name: 2 School of Pharmaceutical and Population Health Informatics (SoPPHI), DIT University, Dehradun 248009, India – name: 6 Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi Arabia – name: 10 Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/36015337$$D View this record in MEDLINE/PubMed |
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| Copyright | COPYRIGHT 2022 MDPI AG 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. 2022 by the authors. 2022 |
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| Keywords | alginate chitosan breast cancer nanoparticle β–sitosterol phytosterol |
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| Snippet | β−sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products,... β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products,... |
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| SubjectTerms | alginate Analysis Biocompatibility Breast cancer Cancer therapies Care and treatment Chemotherapy chitosan Chloride Diagnosis Drug delivery systems Electronic equipment and supplies Females Health aspects Laboratories nanoparticle Nanoparticles Particle size phytosterol Phytosterols Plastic embedment Polymers Quantum dots Reagents Sodium β–sitosterol |
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| Title | A β-Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer |
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