Multi-factor optimization and interaction analysis for enhanced nanobubble formulation and performance of Dasatinib

被引:0
|
作者
Boddu, Kishore Kumar [1 ]
Gubbiyappa, Kumar Shiva [1 ]
机构
[1] GITAM, GITAM Sch Pharm, Patencheru 502329, Telangana, India
关键词
Cellular uptake; cytotoxicity; Drug release; Hemolysis; Solubility; CYCLODEXTRIN NANOSPONGES; PLGA; NANOPARTICLES; MICROBUBBLES;
D O I
10.1016/j.jddst.2024.106112
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The objective of this study was to develop and optimize PLGA nanobubbles as a delivery system for dasatinib. In this study, we developed nanobubbles with a perfluoropentane core and a PLGA outer shell, optimizing their properties using a three-level Box-Behnken design. We thoroughly examined the physical and chemical attributes of dasatinib-loaded nanobubbles, including size, surface charge, and structure, and assessed drug encapsulation and release, as well as investigating cell uptake and antitumor effectiveness. The encapsulation efficiency, particle size, and zeta potential of the nanobubbles varied from 15.12 % to 69.23 %, 96.78 nm-767.72 nm, and-38.56 mV to-12.34 mV, respectively, in 29 trials using a Box-Behnken design. Employing Response Surface Methodology, we optimized the formulation, resulting in an ideal combination: 160.35 mg dasatinib, 500 mg PLGA, 2.0 % w/v PVA, and stirring at 6000 rpm, achieving a high global desirability value of 0.971. These nanobubbles demonstrated an encapsulation efficiency of 80.12 % and a loading capacity of 24.34 %, with a low viscosity of 6.1 cP. Nanobubbles showed notable differences in drug release with and without ultrasound. Under sonication, 59.42 % of dasatinib was released in 6 h compared to 35.34 % without sonication, and after 24 h, 76.89 % was released without ultrasound, while nearly 99.58 % was released with ultrasound. Stability tests at different temperatures showed consistent encapsulation efficiency and particle size, especially at lower temperatures. Safety evaluations indicated no hemolysis, and cellular uptake studies revealed around a 2.5-fold increase in fluorescence intensity in cells exposed to Dasatinib Nanobubbles with ultrasound. Cytotoxicity tests demonstrated enhanced sensitivity, with IC50 values of 86.82 mu M for free dasatinib, 63.58 mu M for nano- bubbles without ultrasound, and 44.58 mu M for nanobubbles with ultrasound. The PLGA nanobubbles efficiently encapsulated dasatinib, boosting cellular uptake and cytotoxicity, underscoring their potential for enhanced cancer therapy, particularly with ultrasound.
引用
收藏
页数:14
相关论文
共 50 条
  • [1] Intensification of quercetin nanobubble formulation and performance by multi-factor optimization and interaction analysis
    Kumar, A. V. Hema
    Kantlam, Chamakuri
    PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY, 2025, 30 (01) : 10 - 24
  • [2] Factor interaction in multi-factor systems
    Trakhtengerts, E.A.
    Zhongxing Jixie/Heavy Machinery, 1998, (06): : 3 - 52
  • [3] Enhanced Multi-factor Authentication on the Cloud
    Alyounis, Essa
    Dinah, Quanq
    INNOVATION MANAGEMENT AND SUSTAINABLE ECONOMIC COMPETITIVE ADVANTAGE: FROM REGIONAL DEVELOPMENT TO GLOBAL GROWTH, VOLS I - VI, 2015, 2015, : 69 - 77
  • [4] Analysis of landing performance and multi-factor effects with lunar lander
    Wan, Junlin
    Nie, Hong
    Li, Lichun
    Chen, Jinbao
    Zeng, Fuming
    Nanjing Hangkong Hangtian Daxue Xuebao/Journal of Nanjing University of Aeronautics and Astronautics, 2010, 42 (03): : 288 - 293
  • [5] Multi-Factor Optimization and Factor Interactions during Product Innovation
    Hron, Jan
    Macak, Tomas
    AGRARIAN PERSPECTIVES: THE 100TH ANNIVERSARY OF CZECH AGRI-ECONOMIC RESEARCH: INNOVATION AND COMPETITIVENESS OF THE EU AGRARIAN SECTOR, 2012, : 191 - 197
  • [6] Dynamic performance analysis of ball bearings with multi-factor coupling excitation
    Wang, Mingkai
    Yan, Ke
    PRECISION ENGINEERING-JOURNAL OF THE INTERNATIONAL SOCIETIES FOR PRECISION ENGINEERING AND NANOTECHNOLOGY, 2024, 89 : 70 - 90
  • [7] MULTI-FACTOR COUPLING ANALYSIS OF ALTITUDE PERFORMANCE OF LUBRICATION SYSTEM IN HELICOPTER
    Li Ming
    Gao Hongxia
    Yu Jianzu
    Zhou Yi
    Niu Xuemin
    PROCEEDINGS OF THE ASME INTERNATIONAL HEAT TRANSFER CONFERENCE - 2010, VOL 2: CONDENSATION, CONVECTION, MELTING AND SOLIDIFICATION, 2010, : 763 - 768
  • [8] Multi-Factor Analysis and Combination Optimization Design of Subway Train Travel Speed
    Deng, Zihuan
    Hu, Hua
    Liu, Xiulian
    RESILIENCE AND SUSTAINABLE TRANSPORTATION SYSTEMS: PROCEEDINGS OF THE 13TH ASIA PACIFIC TRANSPORTATION DEVELOPMENT CONFERENCE, 2020, : 322 - 328
  • [9] Study on the preparation and properties of high-performance foamed cement by multi-factor optimization
    Zhang, Jian
    Li, Yuliang
    Hang, Zhibin
    Zong, Chaoyang
    Xu, Tao
    Feng, Tugen
    CONSTRUCTION AND BUILDING MATERIALS, 2024, 447
  • [10] Robust Portfolio Optimization with Multi-Factor Stochastic Volatility
    Yang, Ben-Zhang
    Lu, Xiaoping
    Ma, Guiyuan
    Zhu, Song-Ping
    JOURNAL OF OPTIMIZATION THEORY AND APPLICATIONS, 2020, 186 (01) : 264 - 298