Microbubbles (MBs) are microscopic gas-filled bubbles with diameters ranging from 1 to 10µm, commonly used in medical applications such as drug delivery and ultrasound-based imaging. Their unique properties, including a large surface area and responsiveness to ultrasound, make them promising candidates for targeted therapeutic treatments, particularly in diseases such as cancer, hypertension, and heart conditions. This study investigates the preparation, characterization, and potential applications of microbubbles for the targeted delivery of Nicardipine, an antihypertensive drug used in the treatment of hypertension. The microbubbles are composed of a stabilizing albumin shell, encapsulating Nicardipine within the core. A series of techniques, including emulsification, sonication, and heat treatment, are employed to form and stabilize the microbubbles, which are then characterized using optical microscopy and optical spectroscopy for size distribution and concentration. The stability and behavior of the microbubbles under ultrasound exposure are also assessed to evaluate their effectiveness in drug delivery and imaging. The study aims to provide insights into the optimization of microbubble formulations for enhancing therapeutic efficacy while minimizing side effects in hypertension treatment. Additionally, the potential for using microbubbles in combination with ultrasound as a non-invasive method for monitoring blood pressure and improving drug absorption in targeted tissues is explored. These findings could contribute to the development of advanced drug delivery systems, offering a new approach to managing hypertension and related cardiovascular diseases.[5]
Introduction
1. Microbubbles (MBs)
Definition: Microbubbles are gas-filled spheres (1–10 μm) with an inner gas core, outer liquid phase, and a stabilizing shell.
Applications: Widely used in medical imaging and drug delivery, particularly in cancer, diabetes, and heart disease treatment.
Advantages: Large surface area, ultrasound responsiveness, biocompatibility, and targeted delivery capabilities.
2. Hypertension
Definition: A chronic condition with systolic BP ≥ 130 mm Hg or diastolic BP ≥ 80 mm Hg.
Health Impact: Major risk factor for stroke, heart disease, kidney disease, and increased mortality.
Stages:
Normal: <120/<80 mm Hg
Elevated: 120–129/<80 mm Hg
Stage 1: 130–139/80–89 mm Hg
Stage 2: ≥140/≥90 mm Hg
Hypertensive Crisis: >180/120 mm Hg
Symptoms (at severe stages):
Headaches, chest pain, vision changes, dizziness, fatigue, palpitations, etc.
Concentration & Stability: Assessed via spectroscopy and ultrasound imaging
Performance: Verified using ultrasonography and microbubble detection tests
9. Results & Observations
Shape: Spherical
Size: 5–10 μm
Stability: Improved through sonication and heat treatment
Potential: Effective for targeted Nicardipine delivery in hypertension management
Conclusion
In conclusion, microbubbles (MBs) represent a promising and innovative tool in the field of medical treatment, particularly for drug delivery and imaging. Their unique structure, consisting of a gas-filled core surrounded by a biocompatible stabilizing shell, enables efficient therapeutic targeting and enhances the effectiveness of ultrasound in both diagnostic and therapeutic applications. This study demonstrated that the combination of Nicardipine, a calcium channel blocker, with albumin-coated microbubbles offers a novel approach to treating hypertension. The preparation of these microbubbles through emulsification, sonication, and heat treatment successfully encapsulated Nicardipine within the microbubbles, preserving both the drug\'s activity and the stability of the microbubble formulation.
Characterization of the microbubbles revealed a consistent size distribution, suitable for circulation within the bloodstream, and their stability was maintained under ultrasound exposure, suggesting their potential for safe, non-invasive, and targeted drug delivery. Additionally, the ability of microbubbles to improve drug absorption and provide real-time imaging could revolutionize the treatment of hypertension and other cardiovascular diseases, offering greater precision in monitoring and controlling blood pressure.
This study underscores the importance of optimizing microbubble formulations for enhanced therapeutic outcomes and provides a foundation for future research exploring the broader applications of microbubbles in medical fields. By addressing critical issues such as drug stability, microbubble size, and ultrasound responsiveness, further development of microbubble-based drug delivery systems holds the potential to significantly improve the management of hypertension, reduce side effects, and enhance patient outcomes in cardiovascular therapy.
References
[1] Xiujuan Jiang et al. Hypertens Res. Low-intensity focused ultrasound combined with microbubbles for non-invasive downregulation of rabbit carotid body activity in the treatment of hypertension 2024 Nov.
[2] Sophie Hernot, Alexander L. Klibanov. Microbubbles in ultrasound-triggered drug and gene delivery.
[3] Naser, Iman Hussein; Alkareem, Zahraa Abd; Mosa, Amal Umran. Hyperlipidemia: pathophysiology, causes, complications, and treatment. A review. 1,2
[4] Eleanor Stride and Mohan Edirisinghe, Novel microbubble preparation technologies.
[5] Shashank Sirsi, Mark Borden, Microbubble Compositions, Properties and Biomedical Applications.
[6] Aaqib H. Khan, SwarupkumarSurwase, Xinyue Jiang, Mohan Edirisinghe, Sameer V. Dalvi Enhancing In Vitro Stability of Albumin Microbubbles Produced Using Microfluidic T-Junction Device.
[7] Meifang Zhou, Francesca Cavalieri &Muthupandian Ashokkumar Modification OfThe Size Distribution Of Lysozyme Microbubbles Using A Post-Sonication Technique
[8] K. Song, T. Trudeau, Adwitiya Kar, M. Borden, A. Gutierrez-Hartmann Ultrasound-mediated delivery of siESE complexed with microbubbles attenuates HER2+/- cell line proliferation and tumor growth in rodent models of breast cancer.
[9] Mina Lee, E. Lee, Daeyeon Lee, B. Park Stabilization and fabrication of microbubbles: applications for medical purposes and functional materials.
[10] Motohiro Yasuno, S. Sugiura, S. Iwamoto, M. Nakajima, A. Shono, Kazumi Satoh Monodispersed microbubble formation using microchannel technique.
[11] H. Nie, Zhen Dong, D. Y. Arifin, Yong Hu, Chi?Hwa Wang Core/shell microspheres via coaxial electrohydrodynamic atomization for sequential and parallel release of drugs.
[12] Steliyan Tinkov, G. Winter, C. Coester, R. Bekeredjian New doxorubicin-loaded phospholipid microbubbles for targeted tumor therapy: Part I--Formulation development and in-vitro characterization.
[13] Chengcheng Niu, Zhigang Wang, Guangming Lu, Tianyi M. Krupka, Yang Sun, Yu-fang You, Weixiang Song, H. Ran, Pan Li, Yuanyi Zheng Doxorubicin loaded superparamagnetic PLGA-iron oxide multifunctional microbubbles for dual-mode US/MR imaging and therapy of metastasis in lymph nodes.
[14] X. Liang, Yunxue Xu, Chuang Gao, Yiming Zhou, Nisi Zhang, Z. Dai Ultrasound contrast agent microbubbles with ultrahigh loading capacity of camptothecin and floxuridine for enhancing tumor accumulation and combined chemotherapeutic efficacy
[15] Ching-Hsiang Fan, C. Ting, Hao-Li Liu, Chiung-Yin Huang, Han-Yi Hsieh, T. Yen, Kuo-Chen Wei, C. Ye Antiangiogenic-targeting drug-loaded microbubbles combined with focused ultrasound for glioma treatment.
[16] Hong Chen, J. Hwang Ultrasound-targeted microbubble destruction for chemotherapeutic drug delivery to solid tumors.
[17] S. Ho, E. Barbarese, J. D’Arrigo, C. Smith-Slatas, R. Simon Evaluation of lipid-coated microbubbles as a delivery vehicle for Taxol in brain tumor therapy.
[18] Junxiao Ye, Huining He, J. Gong, W. Dong, Yongzhuo Huang, Jianxin Wang, Guanyi Chen, V. Yang Ultrasound-mediated targeted microbubbles: a new vehicle for cancer therapy
[19] Sana Al-Jawadi, Sachin S. Thaku Ultrasound-responsive lipid microbubbles for drug delivery: a review of preparation techniques to optimize formulation size, stability, and drug loading.
[20] R. Cavalli, Marco Soster, M. Argenziano Nanobubbles: a promising efficient tool for therapeutic delivery.
[21] unfang Chen, Wenfang Liu, Chuanpin Chen Microfluidic method for drug-loaded three-phase microbubbles generation.
[22] Pengfei Zhao, Mingbin Zheng, Caixia Yue, Z. Luo, P. Gong, G. Gao, Zonghai Sheng, Cuifang Zheng, Lintao Cai Improving drug accumulation and photothermal efficacy in tumor depending on size of ICG loaded lipid-polymer nanoparticles.
[23] Dong-ping Guo, Xiao-yu Li, Ping Sun, Yi-bo Tang, Xiu-ying Chen, Qi Chen, Le-ming Fan, Bin Zang, Li-zheng Shao, Xiao-rong Li Ultrasound-targeted microbubble destruction improves the low-density lipoprotein receptor gene expression in HepG2 cells.
[24] Sierra, C. Acosta, Cherry C. Chen, Shih-Ying Wu, M. Karakatsani, Manuel Bernal, E. Konofagou Lipid microbubbles as a vehicle for targeted drug delivery using focused ultrasound-induced blood–brain barrier opening.