1 Introduction

Cellulose is a naturally occurring anionic polysaccharide composed of a linear chain of D-glucose molecules linked by β-1,4-glycosidic bonds [25, 30]. Due to its minimal toxicity and allergenicity, cellulose has been widely used as a biocompatible biomaterial [26]. Furthermore, cellulose can be modified into diverse structures by substituting groups such as alkyl, carboxymethyl, and alkene for the hydroxyl group.

Among various sources of cellulose, the non-edible by-product of tunicate skin (TS) constitutes a promising candidate for engineering applications because it contains a high percentage of cellulose (60%) compared to plant cellulose (30%–50%) [38]. The remaining ~ 40% of TS is primarily protein, with typical impurities such as lignin and hemicellulose [33]. Therefore, tunicate cellulose (TC) is of higher purity than plant-derived cellulose. In South Korea alone, up to 31,326 tons of TS waste are generated annually, creating significant disposal and environmental issues [38]. TC, derived from animals, differs from plant- and bacteria-derived cellulose. Its higher crystallinity index (CrI) (> 0.8) compared to plants (0.74) and bacteria (0.3) indicates a greater alignment of fibers in TC [5, 33, 57]. Specifically, the crystallinity of TC ranges from 85 to 99%, depending on the developmental stage (larval or adult). Its aspect ratio of approximately 80 surpasses that of plant-derived cellulose (~ 10) [32, 33, 56]. This high crystallinity and aspect ratio result in larger nanocrystals with greater thermal stability (TC: 335 °C; plant cellulose: 200–300 °C) [5, 33, 57]. However, high crystallinity also poses challenges, as it makes cellulose less soluble, requiring harsh conditions such as homogenizers or sulfuric acid solutions to promote dissolution. Carboxymethyl groups are commonly introduced to cellulose to address these limitations to increase its solubility and conductivity [12, 21].

Although many external stimuli (ions, pH, light, temperature, etc.) have been proposed as potential drug delivery systems, ultrasound-assisted methods have recently garnered increasing attention as promising agents for the delivery of therapeutic compounds, genetic materials, hormones, and proteins due to their cavitation activity [1, 28, 41]. Cavitation exerts a physical impact that aids in releasing biomolecules and cells while also disrupting the stratum corneum to facilitate the transportation of large molecules.

This study leverages the advantages of TC-based hydrogel to maintain gel pH and viscosity across various temperatures. Additionally, incorporating TC enhances the gel’s conductivity, improving the transmission of ultrasound signals between the device and the skin. Collectively, our findings demonstrated that the generated TC gel possesses a superior capability for molecular release under ultrasound stimulation, highlighting its potential as an efficient delivery material, especially for the ultrasound gel.

2 Materials and methods

2.1 TC extraction

The TS were cut into 1 cm × 1 cm pieces and soaked in 70% (v/v) ethyl alcohol (Duksan) for 24 h before being freeze-dried. The freeze-dried TS was heated at 80 °C in 5% (v/v) sodium hydroxide (NaOH, Samchun) for 24 h to remove residual protein. Acid washing and bleaching were carried out in a 5 L fermenter (Marado-PDA, Bionics) containing 7% (v/v) hydrogen chloride (HCl, Samchun) for 24 h, followed by treatment with 4% (v/v) hydrogen peroxide (H2O2, Samchun). This mixture was stirred for 4 h at 80 °C, and the processed TC was then dried at room temperature.

The cellulose content in TS was analyzed by determining structural carbohydrates and lignin biomass according to laboratory analytical procedures [50]. The TC was treated with 72% (v/v) sulfuric acid (H2SO4, Samchun) at 30 °C for 2 h, followed by treatment with dilute acid (4% (v/v)) at 121 °C for 1 h. The hydrolysis products were determined using high-performance liquid chromatography (HPLC, Shimadzu CBM-40) equipped with an RI detector and a Shodex SP0810 column (Resonac) operated at 85 °C. The mobile phase consisted of deionized water (DW) at a 0.6 mL/min flow rate.

The molecular weights (MW) and degrees of polymerization (DP) of purified TC were determined by gel permeation chromatography (GPC, Agilent 1200S/mini DAWN TREOS) using tetrahydrofuran as a solvent. The TC sample was derivatized with phenyl isocyanate to be dissolved in tetrahydrofuran (Sigma-Aldrich) [27]. To this end, 4 mL of 99.8% (v/v) anhydrous pyridine (Sigma-Aldrich) and 0.5 mL of 98% (v/v) phenyl isocyanate (Kanto Chemical Co.) were added to 15 mg of TC, and the vial was sealed with a Teflon-coated cap. The vial was kept in an oil bath at 70 °C and stirred continuously for 72 h to complete the reaction. The reaction was then stopped by adding 1 mL of methyl alcohol. Subsequently, the resulting mixture was slowly added to 70% (v/v) methyl alcohol (Duksan) to promote precipitation of the derivatized TC. Next, the solid products were collected by filtration, washed with 70% (v/v) methyl alcohol (Duksan), and then washed twice with DW. Ginallt, the thoroughly washed derivatized TC was dried overnight at 65 °C.

2.2 Synthesis of tunicate carboxymethyl cellulose (TCMC)

The purified TC was functionalized into carboxymethyl cellulose (CMC) through homogeneous carboxymethylation using lithium perchlorate (LiClO4•3H2O, Alfa Aesar) as described in a previous study [14] with slight modifications. The TC was stirred with LiClO4•3H2O (1% (w/v)) (Alfa Aesar) and heated to 100 °C in a closed round flask with a magnetic stirrer until the TC was completely dissolved. Sodium hydroxide (0.06% (w/v)) (NaOH, Samchun) and sodium chloroacetate (0.048% (w/v)) (Thermo Fisher Scientific) were then added to the mixture in a stepwise manner, and the reaction was carried out at 100 °C for 1 h. The product was precipitated in methanol, and the recovered precipitate was re-dissolved in 10 mL of DW. The dissolved product was neutralized with acetic acid (Duksan) and re-precipitated with ethyl alcohol. The purification steps were repeated three times, and the final product was dried at room temperature and labeled as TCMC.

2.3 Physicochemical characterization of TCMC

Changes in functional groups in the TCMC were investigated using Fourier-transform infrared spectroscopy (FT-IR). The dried TC and TCMC were ground using a homogenizer, and their FT-IR spectra were determined by averaging 16 scans per spectrum at a 600–2000 cm−1 range (resolution, 4 cm−1; scanning interval, 1 cm−1) using an FT/IR-4100 type A spectrometer (Jasco International Co. Ltd.).

HPLC analyses were conducted to examine the degree of substitution (DS) of TCMC [44]. To hydrolyze TCMC, 0.1 g of TCMC was dispersed in 2 mL of 70% (v/v) perchloric acid (HClO4, Samchun) for 10 min at 25 °C. After the first hydrolysis reaction, the mixture was diluted with 18 mL DW and then incubated at 100 °C for 16 h for additional hydrolysis. After the second hydrolysis reaction, the mixture was cooled to room temperature, neutralized with 2 M potassium hydroxide (KOH, Samchun), and then kept at 4 °C for 1 h to complete the potassium perchlorate (KClO4) precipitation. The precipitated sample was filtered with a 0.2 µm cellulose acetate filter and washed three times with DW. The filtrate was evaporated until the sample volume decreased. The diluted sample was then filtered with a 0.2 µm PVDF filter and used for HPLC analysis. The contents of carboxymethylated glucoses in hydrolyzed TCMC samples were analyzed using HPLC (CBM-40, Shimadzu) equipped with an RI detector and an Aminex HPX-87H column operated at 65 °C. The mobile phase consisted of 5 mM sulfuric acid with a 0.5 mL/min flow rate. The DS of TCMC was calculated as follows:

$${\text{DS}} = 3x_{t} + 2x_{d} + x_{m}$$

where xt, xd, and xm are the mole fraction of tri-carboxylated, di-carboxylated, and mono-carboxylated glucose, respectively.

The X-ray diffraction (XRD) patterns of TC and TCMC were analyzed using an X-ray diffractometer (Smartlab, Rigaku). The samples were scanned in a 2 theta (θ) range of 2–40° at 40 kV and 40 mA. The CrI of cellulose was calculated using the height difference method [45].

2.4 Viscosity, pH, and conductivity measurement of TCMC gel

Viscosity measurements for the TCMC gels were conducted using a viscometer (DV2T, Brookfield) equipped with a plate-shaped spindle (CPA-52Z). The TCMC gels were carefully placed on the cone plate, and the gap between the spindle and the plate was adjusted accordingly. The shear speed was set at 1 rpm for 30 s to ensure consistency, and the temperature was maintained at a constant 25 °C. The viscosity values presented on the graph are denoted in poise (P).

Both pH (Ino lab) and conductivity (BANTE Instruments) were measured under different temperatures (4 °C, 23 °C, and 50 °C). A gel containing only carbopol, triethanolamine, and glycerin without TC was used as the negative control and labeled ‘base gel.’ The ratios of carbopol, triethanolamine, and glycerin in each sample were denoted as numbers after the letters C (carbopol), T (triethanolamine), and G (glycerin).These properties were compared with those of a commercially available gel (Ecosonic, Senipia).

2.5 Ultrasound-induced dye release of TCMC gel

Brilliant blue (Sigma-Aldrich) was added at the initial stage of ultrasound gel mixing. The gel was then washed to remove any uncaptured dye. An ultrasound device with a facial care instrument charger (Protec) was applied to the gel for 15 min. The released dye was measured at 550 nm using a microplate reader (BioTek) every minute for the duration of the application.

3 Results and discussion

3.1 Purification of TC from TS

TC was extracted from TS, after which the cellulose and protein content were measured. The cellulose content was determined using HPLC, the standard method for determining carbohydrates, which calculates it as glucose multiplied by the conversion factor of 0.9. The initial cellulose content in TS was 44.2%, and the purification process successfully reduced the protein content while increasing the cellulose content. Following the deproteination process, the cellulose content of the TS sample increased to 76.6%. The acid-washing process further elevated the cellulose content to 96.3%. Ultimately, TC obtained through the H2O2 bleaching process displayed a cellulose content of over 99%, with protein and ash contents being undetectable (less than 0.01%) (Fig. 1A).

Fig. 1
figure 1

A Extraction and synthesis process of TCMC. B TCMC gel network. TCMC: tunicate carboxymethyl cellulose, DW: deionized water

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The number-average MW (Mn) and weight-average MW (MW) of purified TC, as determined by GPC, were 164,606 and 1,563,427, respectively. The polydispersity index (PDI), calculated by dividing Mw by Mn, was 9.50. The number-average DP (DPn) and weight-average DP (DPw) were obtained by dividing Mn and Mw by 519 g/mol, representing the MW of the tricarbanilated cellulose unit [16]. For TC, the DPn and DPw of TC were 317 and 3012, respectively. The DP values of purified TC exceeded those of various cellulose types, including delignified wood pulp, cotton linter pulp, and bacterial cellulose [6].

3.2 The characterization of TCMC

Carboxymethylation of TC was performed to enhance its hydrophilicity using various classical heterogeneous and homogeneous carboxymethylation methods [50]. However, only the homogeneous carboxymethylation method employing lithium perchlorate successfully yielded water-miscible TCMC. More than 10% (w/v) of TCMC could be fully dissolved in water. The TCMC gel was further formulated with the mix of carbopol, triethanolamine, and glycerin (Fig. 1B).

Changes in the functional groups of TCMC were verified by FT-IR (Fig. 2A). Peaks evident in TC and TCMC were observed at 2939 and 3332 cm−1, ascribed to –CH and –OH groups, respectively. Unique bands exclusively present in TCMC appeared at 1594 and 1417 cm−1, indicating the presence of carboxylate anions (–COO−) and scissoring/bending vibrations of –CH2 groups. These findings support the existence of carboxymethyl substituents [14, 27]. Specific peaks displayed shifts due to carboxymethylation. The FT-IR spectrum band of TC at 1052 cm−1 shifted to 1061 cm−1, whereas the peak at 1031 cm−1 shifted to 1026 cm−1. Both shifts were attributed to β-(1,4)-glycosidic linkages between the carboxymethylated and unmodified glucose units [14].

Fig. 2
figure 2

A FT-IR spectra of tunicate cellulose (TC) and tunicate carboxymethyl cellulose (TCMC). B HPLC chromatogram of glucose, mono-carboxymethyl glucose, di-carboxymethyl glucose, and tri-carboxymethyl glucose in a hydrolyzed TCMC sample. C GPC chromatogram of TC and regenerated TC after dissolution in lithium perchlorate. D XRD patterns of TC and TCMC. FT-IR Fourier-transform infrared spectroscopy, HPLC high-performance liquid chromatography, GPC gel permeation chromatography, XRD X-ray diffraction

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The DS of TCMC was measured through the HPLC (Fig. 2B). The mole fractions of glucose, 2-; 3- and 6-mono-O-carboxymethyl glucose (xm), 2,3-; 2,6- and 3,6-di-O-carboxymethyl glucose (xd), and 2,3,6-tri-O-carboxymethyl glucose (xt) in hydrolyzed TCMC samples were 0.14, 0.38, 0.36, and 0.12, respectively (Fig. 2B). The calculated DS of TCMC was 1.46. These findings unambiguously demonstrate the successful carboxymethylation of TC through homogeneous carboxymethylation using lithium perchlorate. The significant water solubility of TCMC can be attributed to the presence of highly substituted carboxymethyl groups.

In this study, TC was exclusively and homogeneously carboxymethylated using lithium perchlorate. The carboxymethylation of TC might be hindered by its unique higher MW and excellent crystallinity compared to other forms of cellulose. To mitigate these factors, the MW and crystallinity of TC were decreased by dissolving it in lithium perchlorate.

The alteration in the MW of TC due to dissolution in lithium perchlorate was explored by measuring the MW of regenerated TC after its dissolution in lithium perchlorate (Fig. 2C). The Mn and Mw values of the regenerated TC were 114,606 and 505,938, respectively. These values represent a 70% and 32% reduction in the initial values, respectively. The resulting DPn and DPw values of the regenerated TC were 221 and 975, respectively. The PDI value of the regenerated TC also decreased from 9.5 in the original TC to 4.4. The dissolution process of TC in lithium perchlorate substantially diminished the MW of TC while augmenting its uniformity. As a result, the homogeneous dissolution process enhanced the reaction efficiency of carboxymethylation with sodium chloroacetate. The heightened water solubility of TCMC can be partially attributed to reduced internal hydrogen bonding resulting from the lower MW.

TC typically exhibits significantly higher crystallinity compared to other types of cellulose. The high crystalline structure of TC can also limit its functionalization efficiency. Therefore, few functionalization results of TC have been reported. The XRD diagrams of TC showed characteristic peaks of cellulose at 14.6°, 16.6°, 20.5°, 22.8°, and 34.3°. The CrI value of TC calculated from the XRD diagram is 90.1, which is very high compared to other celluloses (Fig. 2D) [6]. The XRD patterns of TCMC showed that the main diffraction peak was shifted and widened at 2θ = 20.7°. The existence of peaks at approximately 2θ = 20° suggested the conversion of the crystal structure into an amorphous state [40]. A CrI value for TCMC could not be determined. The homogeneous carboxymethylation process completely changed the highly crystalline structure of TC into an amorphous state. The high water solubility of TCMC can also be explained by its amorphous structure.

3.3 TCMC ultrasound gel formulation

Ultrasound gel must possess specific physicochemical properties such as viscosity, conductivity, and pH in order for it to effectively transmit signals. Commercial ultrasound gels commonly contain carbopol, triethanolamine, glycerin, and water.

Carbopol is used in biomedical and cosmetic applications due to its thickening, suspending, and stabilizing properties. It comprises polyacrylic acids containing 56%–68% carboxylic acid (–COOH) groups. These groups act as carboxyl donors, forming hydrogen bonds with water molecules. When dispersed in water, carbopol molecules uncoil and increase viscosity, enhancing the gel’s performance [15].

Triethanolamine is another key component in ultrasound gel, as it forms crosslinks with carbopol, further increasing viscosity [4]. The U.S. Food and Drug Administration (FDA) has set a maximum standard of triethanolamine around 5% in solution. Above that, the mild skin irritation was observed [10]. Consequently, the concentration of triethanolamine in this study was kept below 3% in solution.

Glycerin, which readily dissolves in water or alcohol, plays a significant role in the gel’s intricate conformational dynamics and hydrogen bond networks [51]. Therefore, it influences the swelling and viscoelastic properties of the ultrasound gel [52].

In this study, TCMC was incorporated into a mixture of carbopol, triethanolamine, and glycerin, designated as the ‘base gel,’ for experimental purposes. The addition of TCMC to the base gel leads to the formation of more intricate polymer networks through both ionic and hydrogen bonds. The resilient fibers of TCMC enhance gel stability, while its dense network accommodates more water molecules, thereby improving wettability and moisture retention [31, 55]. The gel’s ability to retain water helps prevent rapid and irreversible dehydration during repeated ultrasonic treatments [29].

3.4 Characterization of the TCMC ultrasound gel

As the gel directly interacts with tissue, it must adhere to specific pH levels corresponding to the targeted tissue conditions. The skin typically maintains a pH of 4.0–7.0, and pH level below 2.0 or above 11.0 is considered corrosive or severely irritating to the skin. Skeletal muscle requires a pH range of approximately 6.9–7.4, while cancerous tissue typically thrives within a pH range of 5.8–6.5. Hence, the pH of the gel should be tailored accordingly for optimal effectiveness in each scenario [17, 24]. The TCMC content in various base gels corresponds to different pH ranges, as presented in the table below (Table 1), and some fall around the pH range suitable for skin application.

Table 1 pH of the examined TCMC gel formulations
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Variations in ultrasound gel viscosity directly affect the transmission of vibrations through the skin. Higher viscosity increases fluid flow resistance, slowing down its average velocity [20, 43]. Conversely, lower viscosity encourages faster evaporation, which can hinder the efficient delivery of molecules. Therefore, it is crucial to adjust the gel’s viscosity to suit its intended applications, whether for muscle stimulation, imaging, or drug delivery. The recommended viscosity range within therapeutic contexts typically falls between 200 and 800 P (Fig. 3A) [48].

Fig. 3
figure 3

A Ultrasound gel viscosities according to their intended uses. B Viscosity of commercial and TCMC gels. C Various ranges of tissue conductivity. D Conductivity of commercial gel and TCMC gels. TCMC: tunicate carboxymethyl cellulose. All error bars represent the standard deviations (n = 3) with statistical significance (***p < 0.005)

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BG2T3 and BG5T3 exhibit viscosities of 434.23 P and 358.53 P, respectively, while the commercial gel has a viscosity of approximately 307.63 P (Fig. 3B). The introduction of TCMC alters the rheological properties of the gel due to its relatively high aspect ratio. TC, featuring fibers 5–10 times longer than those in plants (ranging from 1000 to 2000 nm compared to 200–300 nm), contributes to a more tangled structure, thereby increasing gel stiffness and viscosity [9]. Glycerin, functioning as a plasticizer, reduces chain strength and increases molecular spacing, facilitating movement between TCMC and carbomer molecules. Consequently, the interactions between the molecular chains of both TCMC and carbomer are strengthened. These factors contribute to the observed differences in viscosity between the TCMC gel and the base gel (Fig. 3B, Table 1, Table S1) [53].

The abundant hydroxyl groups present in TC confer conductivity to the material and offer numerous reactive sites for the attachment of carboxymethyl groups. TC has an aspect ratio of approximately 80, indicating that its fibers are elonga These findings demonstrate that adding TCMC significantly enhances the gel’s conductivity, maintaining relatively stable performance across a broad temperature range with only minor fluctuations. ted and slender. Additionally, TC exhibits a high specific surface area exceeding 15 times that of plants, ranging from 150 to 170 m2/g, compared to plants, which typically fall around 10 m2/g [32, 56]. The elevated surface energy and reactivity of TC stem from its abundance of polar groups [47]. Furthermore, the carboxymethylation process introduces potent anionic charges to cellulose, leading to electrostatic repulsion [46]. This repulsion plays an important role in determining the viscosity of the suspension and its water solubility [8]. CMC interacts through electrostatic forces with carbopol and triethanolamine present in the base gel [18]. This CMC enhances electrical properties such as conductivity and improves cellulose-based ultrasound gel’s accuracy, precision, and signal transmission [13, 22, 34, 39].

In this study, the conductivity levels of all gel samples were consistent with those found in the therapeutic range for muscle stimulation (Fig. 3C), which typically falls within a 1–10 mS/cm range [36]. Higher proportions of TCMC addition tend to result in more significant increases in gel conductivity. BG2T3, BG4T3, and BG5T3 exhibited conductivity values of 9.41 mS/cm, 10.16 mS/cm, and 8.40 mS/cm, respectively. Conversely, both the commercial and base gel, which do not contain TCMC, exhibited much lower conductivity levels of approximately 1.44 mS/cm, 2.71 mS/cm, 2.47 mS/cm, and 1.13 mS/cm, respectively (Fig. 3D, Table S1). The enhanced conductivity of TCMC-containing gel has important implications for ultrasonic sonophoresis, providing key advantages such as minimal risk of skin damage, the ability to target a wide range of drugs, penetration depths of approximately 5 cm, and rapid treatment durations [35]. Among the various 3% TCMC gels examined herein, BG2T3 was ultimately selected for further experiments.

3.5 BG2T3 stability analysis

Maintaining consistent pH levels is critical for ensuring the gel’s chemical stability, solubility, and electrical conductivity, which is essential for precise signal measurements [1, 42]. A pH mismatch with the skin can compromise the skin barrier and lead to adverse effects. Therefore, it is crucial to maintain pH within the prescribed range under varying environmental conditions. Ensuring viscosity and conductivity is essential to maintaining the gel’s stability and achieving consistent ultrasound-assisted molecular delivery. Fluctuations in viscosity or conductivity can lead to unstable ultrasound wavelengths, resulting in abrupt temperature changes that may cause skin burns or irritation [3].

The gel’s stability at various temperatures (4 °C, 23 °C, and 50 °C) was confirmed over 7 days by monitoring pH, viscosity, and conductivity (Table 2). The pH was maintained within a 4 to 7 range across all temperatures, confirming that the BG2T3 is compatible and suitable for skin-contacting therapies.

Table 2 The pH, viscosity, and conductivity changes of the gel after 7 days
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BG2T3 showed narrow viscosity changes compared to the base gel. This stability is likely due to the rigid cellulose chain maintaining its spatial structure and preventing fluctuations in its rheological behavior [2]. Increasing the DS enhances the molecular charge density, leading to a stabilization effect by surpassing the ion-binding capacity. The degree of polymerization and the viscosity of CMC are largely determined by its average chain length and DS [7], with the longer chain lengths and higher DS of TCMC providing stable viscosity. The addition of TCMC also contributes to stabilizing changes in gel conductivity. The conductivity of BG2T3 varied by less than 20% across temperatures (19.02% at 4 °C, 7.76% at 23 °C, and 1.48% at 50 °C), while the base gel exhibited rapid decreases in conductivity of more than 30% (35.66% at 4 °C, 68.01% at 23 °C, and 55.51% at 50 °C). These findings demonstrate that adding TCMC significantly enhances the gel’s conductivity, maintaining relatively stable performance across a broad temperature range with only minor fluctuations.

3.6 Small molecule delivery with BG2T3-mediated ultrasound

The cavitation effect occurring within the ultrasound gel facilitates the destruction of microbubbles, thereby enhancing the drug release capability. This cavitation effect, responsive to ultrasound energy, allows for effective therapies by stably collapsing microbubbles [49]. Moreover, drug release induced by ultrasound stimulation offers several key advantages, such as controlled drug release from drug delivery carriers, enabling modulation of drug release quantity, absorption, and disease targeting within the body [11]. Accurately regulating drug release has several advantages such as reduced side effects, improved therapeutic efficacy, and enhanced usability [23].

The MW of brilliant blue (854.02 g/mol) contained in the gel is similar to that of the anticancer drug Taxol (854 g/mol). It is comparable to other antiviral agents such as Crixivan (712 g/mol) and the aminoglycoside antibiotic gentamicin (694.7 g/mol) [37]. An ultrasound-based dye molecule delivery system (Fig. 4A) was established to assess the dye molecule dispersal capability of the ultrasound gel, and the dye diffusion of BG2T3 was examined. The results showed that dye release began after the ultrasound treatment, gradually increased, and reached a 54.06% release rate at 11 min (Fig. 4B).

Fig. 4
figure 4

A Ultrasound transmission through the dermal layer (image from BioRender). B Release of dye molecule from BG2T3. TCMC: tunicate carboxymethyl cellulose

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Despite being fast and straightforward, ultrasound therapy poses burn risks due to the self-heating of the device using ultrasound waves, highlighting the need for rapid molecule release. In previous studies, cellulose hydrogel demonstrated increased nicotine release upon the application of ultrasound, releasing over 50% of nicotine within an hour. Another cellulose hydrogel demonstrated 50% propionic acid and butyrate release within 20 min [19, 54]. BG2T3 achieved 50% dye release in 11 min, significantly faster than the two hydrogel examples discussed above. Thus, the TCMC exhibited a promising molecular delivery ability and increased conductivity, especially when combined with ultrasound.

4 Conclusion

Ultrasound gels are tailored for specific use ranges. This study utilized a material derived from tunicate by-products (TS) to produce ultrasound gel. Cellulose extracted from TS was then synthesized with carboxymethyl groups to enhance solubility and wettability. This synthesized material was formulated into ultrasound gel using thickening polymers such as carbopol, glycerin, and triethanolamine. Various formulations of ultrasound gels were assessed for pH, viscosity, and conductivity to optimize conditions suitable for transdermal therapy. Among these formulations, BG2T3 exhibited favorable characteristics, particularly high conductivity attributed to the ionization of carboxymethyl groups. Therefore, the gel that has been developed holds promise as a prospective candidate for ultrasound-based drug release systems.