DEVELOPMENT OF GUGGULSTERONE-LOADED PHYTOSOMES: A QUALITY BY DESIGN-BASED CHARACTERIZATION AND OPTIMIZATION STUDIES

DEVELOPMENT OF GUGGULSTERONE-LOADED PHYTOSOMES: A QUALITY BY DESIGN-BASED CHARACTERIZATION AND OPTIMIZATION STUDIES

Authors

  • Damodharan N SRM College of Pharmacy
  • Jebastin Koilpillai Research Scholar, Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203
  • Jamal Basha Dudekula Research Scholar, Department of Pharmacognosy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203

DOI:

https://doi.org/10.22159/ijap.2024v16i5.51559

Keywords:

Guggulsterones, gum resin of the Commiphora mukul plant, also known as

Abstract

Objective: The primary objective of this study was to enhance drug delivery efficiency through the design and optimization of guggulsterone-phytosomes, employing a 3-factor 3-level Box-Behnken Design.

Methods: The methodology involved a solvent evaporation technique utilizing guggulsterone and soy lecithin, with a systematic variation and optimization of critical factors such as soy lecithin and guggulsterone concentration, alongside temperature adjustments to refine the phytosome formulations. The characterizations of these formulations were extensive, with a particular emphasis on key quality attributes, notably percentage entrapment efficacy and drug release.

Results: The optimized guggulsterone-phytosomes demonstrated impressive outcomes, showcasing a remarkable entrapment efficiency of 92.64% and a noteworthy drug release rate of 91.69% at 24 hours. These formulations displayed heightened viability in selected cell lines, exhibiting Cellular Toxic Concentration with CTC50 ranging from 253.39 to 330.44 µg/ml. Moreover, they exhibited stability under stressed conditions from a physicochemical perspective. The particle size was measured at 137.8 nm, accompanied by a zeta potential of -25.3 mV.

Conclusion: Significantly, the extended drug release from Guggulsterone-phytosomes adhered to first-order kinetics with Fickian diffusion. In summary, this study underscores the efficacy of the Box-Behnken Design in crafting optimized Guggulsterone-phytosomes, showcasing their potential as promising drug delivery carriers. The enhanced drug delivery platform exhibits significant promise in amplifying antihyperlipidemic effects, attributed to the improved performance and stability of these innovative phytosomes

Keywords: Phytosome, Bioavailability, Box–Behnken design, Guggulsterone, Hyperlipidemia, Soy lecithin.

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Author Biographies

Jebastin Koilpillai, Research Scholar, Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203

Research Scholar, Department of Pharmaceutics, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203

Jamal Basha Dudekula, Research Scholar, Department of Pharmacognosy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203

Research Scholar, Department of Pharmacognosy, SRM College of Pharmacy, SRM Institute of Science and Technology, Kattankulathur, Chennai 603203

References

Yusuf A, Almotairy ARZ, Henidi H, Alshehri OY, Aldughaim MS. Nanoparticles as Drug Delivery Systems: A Review of the Implication of Nanoparticles’ Physicochemical Properties on Responses in Biological Systems. Polymers. 2023;15(7):1596. doi: 10.3390/polym15071596

Patra JK, Das G, Fraceto LF, Campos EVR, Rodriguez-Torres MDP, Acosta-Torres LS, et al. Nano based drug delivery systems: recent developments and future prospects. J Nanobiotechnology. 2018;16(1):71. doi.org/10.1186/s12951-018-0392-8

Martínez-Ballesta Mc, Gil-Izquierdo Á, García-Viguera C, Domínguez-Perles R. Nanoparticles and Controlled Delivery for Bioactive Compounds: Outlining Challenges for New “Smart-Foods” for Health. Foods. 2018;7(5):72. doi.org/10.3390/foods7050072

Chi C, Zhang C, Liu Y, Nie H, Zhou J, Ding Y. Phytosome-nanosuspensions for silybin-phospholipid complex with increased bioavailability and hepatoprotection efficacy. Eur J Pharm Sci. 2020;144:105212. doi: 10.1016/j.ejps.2020.105212

Kotta S, Khan AW, Pramod K, Ansari SH, Sharma RK, Ali J. Exploring oral nanoemulsions for bioavailability enhancement of poorly water-soluble drugs. Expert Opin Drug Deliv. 2012;9(5):585–98. doi: 10.1517/17425247.2012.668523

Shriram RG, Moin A, Alotaibi HF, Khafagy ES, Al Saqr A, Abu Lila AS, et al. Phytosomes as a Plausible Nano-Delivery System for Enhanced Oral Bioavailability and Improved Hepatoprotective Activity of Silymarin. Pharmaceuticals (Basel). 2022;15(7):790. doi: 10.3390/ph15070790

Swain B, Koilpillai J, Narayanasamy D. Systematic Review on Recent Advancements and Liposomal Technologies to Develop Stable Liposome. Current Trends in Biotechnology and Pharmacy. 2023;17(1):735–48. doi.org/10.5530/ctbp.2023.1.13

Alharbi WS, Almughem FA, Almehmady AM, Jarallah SJ, Alsharif WK, Alzahrani NM, et al. Phytosomes as an Emerging Nanotechnology Platform for the Topical Delivery of Bioactive Phytochemicals. Pharmaceutics. 2021 Sep;13(9):1475. doi: 10.3390/pharmaceutics13091475

Barani M, Sangiovanni E, Angarano M, Rajizadeh MA, Mehrabani M, Piazza S, et al. Phytosomes as Innovative Delivery Systems for Phytochemicals: A Comprehensive Review of Literature. Int J Nanomedicine. 2021;16:6983–7022. doi: 10.2147/IJN.S318416

Lu M, Qiu Q, Luo X, Liu X, Sun J, Wang C, et al. Phyto-phospholipid complexes (phytosomes): A novel strategy to improve the bioavailability of active constituents. Asian J Pharm Sci. 2019;14(3):265–74. doi: 10.1016/j.ajps.2018.05.011

Jebastin K, Narayanasamy D. Rationale utilization of phospholipid excipients: a distinctive tool for progressing state of the art in research of emerging drug carriers. J Liposome Res. 2023;33(1):1–33. doi: 10.1080/08982104.2022.2069809

Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur J Pharm Sci. 2017;108:36–49. doi: 10.1016/j.ejps.2016.12.009

Zeng Q ping, Liu Z hong, Huang A wen, Zhang J, Song H tao. Preparation and characterization of silymarin synchronized-release microporous osmotic pump tablets. Drug Des Devel Ther. 2016; 10:519–31. doi: 10.2147/DDDT.S91571

Vargas-Mendoza N, Madrigal-Santillán E, Morales-González Á, Esquivel-Soto J, Esquivel-Chirino C, García-Luna y González-Rubio M, et al. Hepatoprotective effect of silymarin. World J Hepatol. 2014; 6(3):144–9. doi: 10.4254/wjh.v6.i3.144

Hooresfand Z, Ghanbarzadeh S, Hamishehkar H. Preparation and Characterization of Rutin-loaded Nanophytosomes. Pharm Sci. 2015; 21(3):145–51. doi:10.15171/PS.2015.29

Surwase SS, Munot NM, Idage BB, Idage SB. Tailoring the properties of mPEG-PLLA nanoparticles for better encapsulation and tuned release of the hydrophilic anticancer drug. Drug Deliv Transl Res. 2017; 7(3):416–27. doi: 10.1007/s13346-017-0372-9

Alshahrani SM. Optimization and Characterization of Cuscuta reflexa Extract Loaded Phytosomes by the Box-Behnken Design to Improve the Oral Bioavailability. J Oleo Sci. 2022;71(5):671–83. doi: 10.5650/jos.ess21318

Alhakamy NA, Badr-Eldin SM, A Fahmy U, Alruwaili NK, Awan ZA, Caruso G, et al. Thymoquinone-Loaded Soy-Phospholipid-Based Phytosomes Exhibit Anticancer Potential against Human Lung Cancer Cells. Pharmaceutics. 2020;12(8):761. doi: 10.3390/pharmaceutics12080761

Yanyu X, Yunmei S, Zhipeng C, Qineng P. The preparation of silybin-phospholipid complex and the study on its pharmacokinetics in rats. Int J Pharm. 2006;307(1):77–82. doi: 10.1016/j.ijpharm.2005.10.001

Blackburn GL, Wollner S, Heymsfield SB. Lifestyle interventions for the treatment of class III obesity: a primary target for nutrition medicine in the obesity epidemic. Am J Clin Nutr. 2010;91(1):289S-292S. doi: 10.3945/ajcn.2009.28473D.

Shattat GF. A Review Article on Hyperlipidemia: Types, Treatments and New Drug Targets. Biomedical and Pharmacology Journal. 2015;7(1):399–409. doi : https://dx.doi.org/10.13005/bpj/504

Rupasinghe HPV, Sekhon-Loodu S, Mantso T, Panayiotidis MI. Phytochemicals in regulating fatty acid β-oxidation: Potential underlying mechanisms and their involvement in obesity and weight loss. Pharmacol Ther. 2016;165:153–63. doi: 10.1016/j.pharmthera.2016.06.005.

Sinal CJ, Gonzalez FJ. Guggulsterone: an old approach to a new problem. Trends Endocrinol Metab. 2002;13(7):275–6. doi: 10.1016/s1043-2760(02)00640-9.

Deng R. Therapeutic effects of guggul and its constituent guggulsterone: cardiovascular benefits. Cardiovasc Drug Rev. 2007;25(4):375–90. doi: 10.1111/j.1527-3466.2007.00023.x.

Urizar NL, Moore DD. G UGULIPID : A Natural Cholesterol-Lowering Agent. Annu Rev Nutr. 2003;23(1):303–13. doi: 10.1146/annurev.nutr.23.011702.073102

Rathee S, Kamboj A. Optimization and development of antidiabetic phytosomes by the Box-Behnken design. J Liposome Res. 2018;28(2):161–72. doi: 10.1080/08982104.2017.1311913.

Das MK, Kalita B. Design and Evaluation of Phyto-Phospholipid Complexes (Phytosomes) of Rutin for Transdermal Application. J app pharm sci. 2014;4(10):51–7. doi: 10.7324/JAPS.2014.401010

Murthy BRS, Yelavarthi PR, Devanna N, Basha DJ. Design of Guggul Lipid Loaded Chitosan Nanoparticles Using Box-Behnken Design – An Evaluation Study. Journal of Pharmaceutical Research International. 2021;53–67. doI: 10.9734/jpri/2021/v33i1831316

Koilpillai J, Narayanasamy D. Development and characterization of novel surface engineered Depofoam: a QbD coupled failure modes and effects analysis risk assessment-based optimization studies. J Liposome Res. 2023;1–17. doi: 10.1080/08982104.2023.2208662.

Shah HA, Patel RP. Statistical modeling of zaltoprofen loaded biopolymeric nanoparticles: Characterization and anti-inflammatory activity of nanoparticles loaded gel. Int J Pharm Investig. 2015;5(1):20–7. doi: 10.4103/2230-973X.147229

Zamora-Mora V, Fernández-Gutiérrez M, Román JS, Goya G, Hernández R, Mijangos C. Magnetic core–shell chitosan nanoparticles: Rheological characterization and hyperthermia application. Carbohydrate Polymers. 2014;102:691–8. doi.org/10.1016/j.carbpol.2013.10.101

Rukmangathen R, Yallamalli IM, Yalavarthi PR. Formulation and biopharmaceutical evaluation of risperidone-loaded chitosan nanoparticles for intranasal delivery. Drug Dev Ind Pharm. 2019;45(8):1342–50. doi: 10.1080/03639045.2019.1619759

Agarwal A, Kharb V, Saharan VA. Process optimisation, characterisation and evaluation of resveratrol-phospholipid complexes using Box-Behnken statistical design. Int Curr Pharm J. 2014;3(7):301–8. doi:10.3329/icpj.v3i7.19079

Hirpara MR, Manikkath J, Sivakumar K, Managuli RS, Gourishetti K, Krishnadas N, et al. Long circulating PEGylated-chitosan nanoparticles of rosuvastatin calcium: Development and in vitro and in vivo evaluations. Int J Biol Macromol. 2018 Feb;107(Pt B):2190–200. doi: 10.1016/j.ijbiomac.2017.10.086

BR SM, Yelavarthi PR, N D. Process of Orlistat-Loaded Chitosan Nanoparticles Using Box–Behnken Design – An Evaluation Study. Asian Journal of Pharmaceutical and Clinical Research. 2021;103–11. doi:10.22159/ajpcr.2021.v14i5.41441

Published

05-07-2024

How to Cite

Damodharan N, Koilpillai, J., & Dudekula, J. B. . (2024). DEVELOPMENT OF GUGGULSTERONE-LOADED PHYTOSOMES: A QUALITY BY DESIGN-BASED CHARACTERIZATION AND OPTIMIZATION STUDIES: DEVELOPMENT OF GUGGULSTERONE-LOADED PHYTOSOMES: A QUALITY BY DESIGN-BASED CHARACTERIZATION AND OPTIMIZATION STUDIES. International Journal of Applied Pharmaceutics, 16(5). https://doi.org/10.22159/ijap.2024v16i5.51559

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