Therapeutic ultrasound alters the physicochemical properties of nanostructured lipid carriers
DOI:
https://doi.org/10.15343/0104-7809.202549e17162025PKeywords:
Ultrasound Therapy, Nanoparticle Drug Delivery Systems, QuercetinAbstract
Quercetin has therapeutic potential in the recovery of musculoskeletal injuries; however, when administered orally, this polyphenol exhibits low absorption. Its skin penetration can be enhanced by nanostructured lipid carriers loaded with quercetin (NLC-Q) applied in combination with pulsed therapeutic ultrasound (PTU). However, different intensities of 1 MHz ultrasound may compromise the physicochemical properties of NLC-Q, and this interaction has not yet been evaluated. The aim of this study was to assess the effects of different 1 MHz PTU intensities on the physicochemical properties of a gel containing nanostructured lipid carriers loaded with quercetin (NLC-Q). NLC-Q was developed using the high shear rate method. PTU (1 MHz, for 5 min, 20% duty cycle) was applied to the gel at intensities of 0.1, 0.2, 0.4, and 0.6 W/cm2 SATA (spatial average temporal average intensity). Physicochemical properties (pH, temperature, mean particle size, polydispersity index, and concentrations of quercetin within the nanostructured lipid carriers) were evaluated before and after the application of different PTU intensities. Intensities of 0.1 and 0.2 W/cm2 SATA did not alter the physicochemical properties of NLC-Q, while intensities of 0.4 and 0.6 W/cm2 SATA increased particle size by 14% and 44%, respectively (P < 0.001). These intensities also increased the polydispersity index by 28% and 88% (P < 0.001). PTU intensities above 0.4 W/cm2 SATA lead to instability of NLC-Q within the gel, which does not favor the topical delivery of the active ingredient.
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Saedi A, Rostamizadeh K, Parsa M, Dalali N, Ahmadi N. Preparation and characterization of nanostructured lipid carriers as drug delivery system: Influence of liquid lipid types on loading and cytotoxicity. Chem Phys Lipids. 2018;216:65–72. https://doi.org/10.1016/j.chemphyslip.2018.09.007
Shamsuddin NAM, Zulfakar MH. Nanostructured Lipid Carriers for the Delivery of Natural Bioactive Compounds. Curr Drug Deliv. 2023;20(2):127- 143. http://dx.doi.org/10.2174/1567201819666220324094234.
Moraes JP de, et al Sonophoresis with nanostructured lipid carrier gel containing quercetin for muscle injury treatment in rats. MLTJ. 2025;15(1):113- 120. http://dx.doi.org/10.32098/mltj.01.2025.13
Pivetta TP, et al. Topical formulation of quercetin encapsulated in natural lipid nanocarriers: Evaluation of biological properties and phototoxic effect. J Drug Deliv Sci Technol. 2019; 53, 101148. https://doi.org/10.1016/j.jddst.2019.101148
Alharbi HOA, Alshebremi M, Babiker AY, Rahmani AH. The role of quercetin, a flavonoid in the management of pathogenesis through regulation of oxidative stress, inflammation, and biological activities. Biomolecules. 2025;15(151):1-56 https://doi.org/10.3390/biom15010151
Sousa Filho LF, Santos MMB, Menezes P dos P, Lima BS, Araújo AAS, Oliveira ED. A novel quercetin/β-cyclodextrin transdermal gel, combined or not with therapeutic ultrasound, reduces oxidative stress after skeletal muscle injury. RSC Adv. 2021;11:27837–27844. https://doi.org/10.1039/D1RA04708F
Izadifar Z, Babyn P, Chapman D. Mechanical and biological effects of ultrasound: a review of present knowledge. Ultrasound Med Biol. 2017;43(6):1085– 1104. https://doi.org/10.1016/j.ultrasmedbio.2017.01.023
Hauck M, et al. Intensity-dependent effect of pulsed and continuous therapeutic ultrasound on endothelial function: A randomised crossover clinical trial. Int J Ther Rehabil. 2019; 26(12):1-12. https://doi.org/10.12968/ijtr.2018.0049
Hauck M, et al. Comparison of the effects of 1 MHz and 3 MHz therapeutic ultrasound on endothelium-dependent vasodilation of humans: a randomised clinical trial. Physiotherapy (United Kingdom). 2019;105(1):120–125. https://doi.org/10.1016/j.physio.2017.08.010
Signori LU, et al. Effects of therapeutic ultrasound on endothelial function of patients with type 2 diabetes mellitus randomized clinical trial. Brazilian J Med Biol Res. 2023; 56, 1–8. https://doi.org/10.1590/1414-431X2023e12576
Martins CN, et al. Effects of cryotherapy combined with therapeutic ultrasound on oxidative stress and tissue damage after musculoskeletal contusion in rats. Physiotherapy (United Kingdom). 2016;102(4):377-383. https://doi.org/10.1016/j.physio.2015.10.013
Belk JW, Kraeutler MJ, Houck DA, Goodrich JA, Dragoo JL, McCarty EC. Platelet-rich plasma versus hyaluronic acid for knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials. Am J Sports Med. 2021;49(1): 249–260. https://doi.org/10.1177/0363546520909397
Cruz JM, et al. Effects of different therapeutic ultrasound waveforms on endothelial function in healthy volunteers: a randomized clinical trial. Ultrasound Med Biol. 2016;42(2):471–480. http://linkinghub.elsevier.com/retrieve/pii/S0301562915005888
Marathe D, Bhuvanashree VS, Mehta CH, Ashwini T, Nayak UY. Low-Frequency Sonophoresis: A Promising Strategy for Enhanced Transdermal Delivery. Adv Pharmacol Pharm Sci. 2024;5:1247450. https://doi.org/10.1155/2024/1247450
Azagury A, Khoury L, Enden G, Kost J. Ultrasound mediated transdermal drug delivery. Adv Drug Deliv Rev. 2014;72:127–143. http://dx.doi. org/10.1016/j.addr.2014.01.007
Seah BCQ, Teo BM. Recent advances in ultrasound-based transdermal drug delivery. Int J Nanomedicine. 2018;13:7749–7763. http://dx.doi. org/10.2147/IJN.S174759
Park D, Park H, Seo J, Lee S. Sonophoresis in transdermal drug deliverys. Ultrasonics. 2014;54(1):56–65. http://dx.doi.org/10.1016/j.ultras.2013.07.007
Moraes JP de, et al. Development and stability of a nanostructured lipid carrier loaded with quercetin incorporated in a gel for transdermal use. Discip Sci - Ciências Nat e Tecnológicas. 2021;22(3),113–134. https://doi.org/10.37779/nt.v22i3.4108
Czajkowska-Kośnik A, Szekalska M, Winnicka K. Nanostructured lipid carriers: A potential use for skin drug delivery systems. Pharmacol Reports. 2019; 71(1):156–166. https://doi.org/10.1016/j.pharep.2018.10.008
Chowdhury SM, Abou-Elkacem L, Lee T, Dahl J, Lut AM. Ultrasound and microbubble mediated therapeutic delivery: Underlying mechanisms and future outlook. J Control Release. 2020; 10(326):75–90. https://doi.org/10.1016/j.jconrel.2020.06.008
Yusof NSM, Babgi B, Alghamdi Y, Aksu M, Madhavan J, Ashokkumar M. Physical and chemical effects of acoustic cavitation in selected ultrasonic cleaning applications. Ultrason Sonochem. 2016;29:568–576. http://dx.doi.org/10.1016/j.ultsonch.2015.06.013
Khosa A, Reddi S, Saha RN. Nanostructured lipid carriers for site-specific drug delivery. Biomed Pharmacother. 2018;103:598–613. https://doi. org/10.1016/j.biopha.2018.04.055
Lesjak M, Beara I, Simin N, Pintać D, Majkić T, Bekvalac K, Orčić D, Mimica-Dukić N. Antioxidant and anti-inflammatory activities of quercetin and its derivatives. Journal of Functional Foods. 2018;40:68-75. https://doi.org/10.1016/j.jff.2017.10.047
Sirsi SR, Borden MA. State-of-the-art materials for ultrasound-triggered drug delivery. Adv Drug Deliv Rev. 2014;72:3–14. http://dx.doi.org/10.1016/j. addr.2013.12.010
Kooiman K, et al. Ultrasound-Responsive Cavitation Nuclei for Therapy and Drug Delivery. Ultrasound Med Biol. 2020;46(6):1296–1325. https://doi. org/10.1016/j.ultrasmedbio.2020.01.002
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