A β–Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer
Obaid Afzal,
Md Habban Akhter,
Irfan Ahmad,
Khursheed Muzammil,
Adam Dawria,
Mohammad Zeyaullah,
Abdulmalik S. A. Altamimi,
Habibullah Khalilullah,
Shehla Nasar Mir Najib Ullah,
Mohammad Akhlaquer Rahman,
Abuzer Ali,
Naiyer Shahzad,
Mariusz Jaremko,
Abdul-Hamid Emwas,
Ibrahim Abdel Aziz Ibrahim
Affiliations
Obaid Afzal
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Md Habban Akhter
School of Pharmaceutical and Population Health Informatics (SoPPHI), DIT University, Dehradun 248009, India
Irfan Ahmad
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Khalid University, Abha 62521, Saudi Arabia
Khursheed Muzammil
Department of Public Health, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha 62521, Saudi Arabia
Adam Dawria
Department of Public Health, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha 62521, Saudi Arabia
Mohammad Zeyaullah
Department of Basic Medical Science, College of Applied Medical Sciences, Khamis Mushait Campus, King Khalid University, Abha 62521, Saudi Arabia
Abdulmalik S. A. Altamimi
Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Habibullah Khalilullah
Department of Pharmaceutical Chemistry and Pharmacognosy, Unaizah College of Pharmacy, Qassim University, Unaizah 51911, Saudi Arabia
Shehla Nasar Mir Najib Ullah
Department of Pharmacognosy, Faculty of Pharmacy, King Khalid University, Abha 62521, Saudi Arabia
Mohammad Akhlaquer Rahman
Department of Pharmaceutics and Industrial Pharmacy, College of Pharmacy, Taif University, Taif 21974, Saudi Arabia
Abuzer Ali
Department of Pharmacognosy, College of Pharmacy, Taif University, P.O. Box 11099, Taif 21944, Saudi Arabia
Naiyer Shahzad
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
Mariusz Jaremko
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
Abdul-Hamid Emwas
Core Labs, King Abdullah University of Science and Technology (KAUST), Thuwal 23955, Saudi Arabia
Ibrahim Abdel Aziz Ibrahim
Department of Pharmacology and Toxicology, Faculty of Medicine, Umm Al-Qura University, Makkah 21955, Saudi Arabia
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.
