Controlled Drug Delivery Applications Research Articles

Kinetic and thermodynamic analysis of engineered alginate–chitosan hydrogel based scaffolds for drug delivery applications

The synthesis of stimulus–responsive hydrogel–based scaffolds has been extensively investigated for controlled drug delivery applications. This study focused on synthesizing alginate and chitosan–based scaffolds for potential use in releasing antibiotic antimycotic solution (AAS) drugs. The controlled release of AAS from AAS–loaded alginate–chitosan scaffolds was investigated under distinct temperatures viz. 37 °C, 25 °C, and 10 °C, labeled as scaffolds A, B, and C, respectively. Porosity assessment revealed consistent and substantial mean porosity percentage of 95.06 ± 2.01 % across all scaffolds. The lower temperature of 10 °C significantly contributed to a gradual and consistent cumulative release of 91.67 ± 1.47 %, compared to 37 °C (94.07 ± 1.89 %) and 25 °C (92.75 ± 1.51 %). The Korsmeyer–Peppas model exhibited high R2 values (0.98, 0.97 to 0.99) for scaffolds A, B, and C, indicating its suitability for describing the in–vitro release of AAS. Furthermore, the obtained release exponent values (0.60, 0.65, and 0.72 for scaffolds A, B, and C, respectively) suggest non–Fickian diffusion as the primary mechanism governing drug release. The release was also pH–dependent, with slower release at acidic (pH 3) and faster release under basic conditions (pH 8) due to varying swelling ratios. Evaluation of thermodynamic parameters viz. Ea, ΔG, ΔH and ΔS, using the rate constant of the Korsmeyer–Peppas model, revealed positive values of ΔH > 0 and ΔS > 0, indicating the prevalence of hydrophobic interactions in the release process.

Probing the inner structure and dynamics of pH-sensitive block copolymer nanoparticles with nitroxide radicals using scattering and EPR techniques

This research emphasizes the crucial role of electron paramagnetic resonance (EPR) spectroscopy in nanoparticle analysis, showcasing its distinctive ability to probe molecular-level details. We demonstrate the synthesis and self-assembly of a new class of pH-responsive amphiphilic diblock copolymers, specifically poly[N-(2-hydroxypropyl)-methacrylamide]-block-poly[2-(diisopropylamino)ethyl methacrylate] (PHPMA-b-PDPA), incorporating 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radicals covalently bound to the hydrophilic PHPMA segment. The copolymer synthesis involved a three-step process, combining reversible addition − fragmentation chain transfer (RAFT) polymerization with carbodiimide (DCC) chemistry. TEMPO radical-containing nanoparticles (RNPs) were created using microfluidic (MF) nanoprecipitation, a technique essential for generating uniform nanoparticles with predictable biodistribution and cellular uptake. Adjusting MF protocol parameters allowed fine-tuning of RNP sizes. EPR spectroscopy confirmed the formation of core–shell RNPs, with features aligning closely with those obtained from scattering techniques like dynamic light scattering (DLS), static light scattering (SLS), small-angle X-ray scattering (SAXS), and cryo-transmission electron microscopy (cryo-TEM). EPR spectroscopy emerges as a potent tool for molecular-level analysis of colloidal polymer systems. This study highlights the EPR-spin label method’s efficacy in probing the internal structural features and dynamics of core–shell nanoparticles, especially their response to pH-triggered disassembly. The findings open new avenues for the use of pH-responsive TEMPO-labeled diblock copolymers in controlled drug delivery applications.

Flaxseed (Linum usitatissimum) mucilage: A versatile stimuli–responsive functional biomaterial for pharmaceuticals and healthcare

The present review is novel as it discusses the main findings of researchers on the topic and their implications, as well as highlights the emerging research in this particular area and its future prospective. The seeds of Flax (Linum usitatissimum) extrude mucilage (FSM) that has a diverse and wide range of applications, especially in the food industry and as a pharmaceutical ingredient. FSM has been blended with several food and dairy products to improve gelling ability, optical properties, taste, and user compliance. The FSM is recognized as a foaming, encapsulating, emulsifying, suspending, film–forming, and gelling agent for several pharmaceutical preparations and healthcare materials. Owing to stimuli (pH) –responsive swelling–deswelling characteristics, high swelling indices at different physiological pHs of the human body, and biocompatibility, FSM is considered a smart material for intelligent, targeted, and controlled drug delivery applications through conventional and advanced drug delivery systems. FSM has been modified through carboxymethylation, acetylation, copolymerization, and electrostatic complexation to get the desired properties for pharma, food, and healthcare products. The present review is therefore devoted to the isolation techniques, structural characterization, highly valuable properties for food and pharmaceutical industries, preclinical and clinical trials, pharmacological aspects, biomedical attributes, and patents of FSM.

Lignin‐based polyurethane composites enhanced with hydroxyapatite for controlled drug delivery and potential cellular scaffold applications

AbstractPolymer technology has rapidly advanced across diverse domains, particularly in biomedical applications. Among various polymers, polyurethane (PU) hold great potential in developing biomaterials such as biomedical scaffold and drug delivery. In this study, we have innovatively engineered eco‐friendly polyurethane using lignin, a sustainable bio‐polyol derived from oil palm empty fruit bunches. To enhance the physicochemical properties of the PU, we have incorporated hydroxyapatite (HA) into the composites. The inclusion of HA has led to notable improvements in crucial properties such as density, porosity, and water absorption, making these composites ideal candidates for tissue regeneration scaffolds. Furthermore, to assess their biomedical applicability in drug delivery and cell scaffolding, we have employed the quercetin drug model. The results revealed a sustained kinetic release behavior within the polyurethane/hydroxyapatite (PU/HA) composites, showcasing their potential for controlled drug delivery applications. Moreover, cytotoxicity assays conducted using neuro‐2a cell models demonstrated the non‐cytotoxic nature of both PU and PU/HA composites. This finding holds significant implications for biomedical applications, indicating that these composites offer biocompatible platforms for tissue engineering and regenerative medicine endeavors. The ability of these composites to support cell viability underscores their potential for a wide range of biomedical applications, including neural tissue engineering and drug delivery systems targeting brain diseases. These findings pave the way for the development of innovative and sustainable biomaterials with diverse biomedical applications.Highlights An eco‐friendly polyurethane has been engineered by harnessing liginin‐derived oil palm empty fruit bunches. Incorporation of hydroxyapaptite enhance the physical properties of polyurethane. Controlled kinetic drug release is one of polyurethane/hydroxyapatite (PU/HA) composites features. The PU/HA composites has low cytotoxicity against neuro‐2a cells.

Preparation and Evaluation of Ranitidine Hydrochloride Floating Microspheres

<i>Introduction</i>: Ranitidine hydrochloride, a member of the H2-receptor antagonist class, is widely employed in treating gastrointestinal conditions like ulcers, gastroesophageal reflux disease (GERD) and Zollinger-Ellison syndrome by reducing gastric acid production. Microspheres, designed for extended drug delivery and enhanced bioavailability, were formulated and evaluated in this study. <i>Aim</i>: To develop ranitidine hydrochloride microspheres capable of prolonging drug delivery and improving bioavailability. Methods: The inotropic gelation method was utilized to prepare alginate microspheres incorporating polymers such as ethyl cellulose, sodium carboxymethyl cellulose, HPMC, and carbopol®. The resulting drug-loaded microspheres exhibited spherical rigidity after cross-linking with a 10% w/v calcium chloride solution. Evaluation parameters including Fourier transform infra-red (FTIR) analysis, precompression characteristics, percentage yield, swelling index, and drug content were determined. <i>Results</i>: The FTIR results obtained, showed there was no incompatibility among the excipients and the active pharmaceutical ingredient. The Scanning electron microscopy (SEM) obtained, indicated the presence of spherical particles present in the formulation. The pre-compression evaluation showed that the angle of repose ranged from 4.85 ± 0.02 to 7.22 ± 0.06o for batched F4 and F1 respectively, while the Carr’s index ranged from 73.5 ± 2.47% to 87.00 ± 3.53% for batches F-7 and F-1 respectively. The percentage yield ranged from 73.5 ± 2.47% to 87.00 ± 3.53% for batches F-7 and F-1 respectively. <i>In vitro</i> drug release studies revealed sustained drug release over 4 hours, with a maximum release of 69.50 ± 1.77% observed for batch F-1. <i>Conclusion</i>: Overall, the formulated ranitidine hydrochloride microspheres demonstrated prolonged and controlled release characteristics, indicating their potential for use in controlled drug delivery applications.

MgSiO3 Fiber Membrane Scaffold with Triggered Drug Delivery for Osteosarcoma Synergetic Therapy and Bone Regeneration.

In this research, a novel MgSiO3 fiber membrane (MSFM) loaded with indocyanine green (ICG) and doxorubicin (DOX) was prepared. Because of MgSiO3's unique lamellar structure composed of a silicon-oxygen tetrahedron, magnesium ion (Mg2+) moves easily and can be further replaced with other cations. Therefore, because of the positively charged functional group of ICG, MSFM has a rather high drug loading for ICG. In addition, there is electrostatic attraction between DOX (a cationic drug) and ICG (an anionic drug). Hence, after loading ICG, more DOX can be adsorbed into MSFM because of electrostatic interaction. The ICG endows the MSFM outstanding photothermal therapy (PTT) performance, and DOX as a chemotherapeutic drug can restrain tumor growth. On the one hand, H+ exchanged with the positively charged DOX based on the MgSiO3 special lamellar structure. On the other hand, the thermal effect could break the electrostatic interaction between ICG and DOX. Based on the above two points, both tumor acidic microenvironment and photothermal effect can trigger DOX release. What's more, in vitro and in vivo antiosteosarcoma therapy evaluations displayed a superior synergetic PTT-chemotherapy anticancer treatment and excellent biocompatibility of DOX&ICG-MSFM. Finally, the MSFM was proven to greatly promote cell proliferation, differentiation, and bone regeneration performance in vitro and in vivo. Therefore, MSFM provides a creative perspective in the design of multifunctional scaffolds and shows promising applications in controlled drug delivery, antitumor performance, and osteogenesis.

Radiation synthesis and characterization of pH-Responsive sodium Alginate/Poly(acrylic acid) nanogel loaded with ferulic acid for anticancer drug delivery

This study focuses on the synthesis and characterization of a pH-responsive nanogel system composed of sodium alginate (NaAlg) and poly(acrylic acid) loaded with ferulic acid. The mechanism of nanogel formation by gamma irradiation was elucidated, highlighting the role of polymer interactions and crosslinking agents. The pHdependent release of ferulic acid from the nanogel carrier was investigated, revealing a controlled release behavior in response to pH variations. The zeta potential values remained slightly negative across the pH range, indicating the presence of surface functional groups. Transmission electron microscopy confirmed the nanogel's formation and uniform particle size at pH 1. This nanogel was considered for controlled drug delivery applications, exhibiting high physical and chemical stability of ferulic acid. Our nanogel compound 5 decreased IC50 against HepG2, A549, MCF-7 and HCT-116 by 58.22 %, 78.35 %, 45.81 %, and 47.94 % respectively. Additionally, it decreased IC50 against VEGFR2 and EGFRT790 M by 41.94 %, and 70.59 % respectively.

A Brief Study on Nanogel: A Review

Strong nanoparticles called nanogels may be utilized in controlled drug delivery applications to distribute active pharmaceutical ingredients. Because of their chemical makeup and formulations that are unsuited for other formulations, nanogels provide a safer and more effective drug delivery mechanism for both hydrophilic and hydrophobic medicines. Functionalized nanoparticles, which serve as drug carriers and can be loaded with medications and other active materials to be released in a regulated way at a specific spot, can now be larger thanks to nanogel technology. The objective of this paper is to present a broad overview of nanogels, their innovative applications across several domains, and their latest synthesis process.

Stimuli-responsive azo-functionalized non-ionic amphiphiles for controlled drug delivery applications

A series of stimuli-responsive non-ionic amphiphiles have been synthesized consisting of n-alkyl/fluoroalkyl chain to impart lipophilicity, and lactose/polyethylene glycol units which confers hydrophilicity. To execute the release of encapsulated guest in a controlled manner, the azo and ester functionalities were incorporated in the synthesized amphiphiles. The ability of the azo unit to undergo trans–cis-trans spatiotemporal isomerization under UV irradiation with subsequent release of the encapsulated guest has been studied in the aqueous solution of amphiphiles at 365 and 254 nm. Furthermore, an immobilized enzyme Candida antarctica lipase (Novozym 435), a hydrolase, was observed to facilitate the cleavage of the ester moiety of the synthesized amphiphiles resulting in the gradual collapse of the nano-aggregates and subsequent release of encapsulated guest. The aggregation and guest encapsulation behaviour of synthesized azo-functionalized amphiphiles were studied by dynamic light scattering (DLS), critical micelle concentration (CMC), and transmission electron microscopy, fluorescence and UV–Vis spectroscopy. Entrapment of hydrophobic drug/dye i.e. curcumin/Nile red in the lipophilic core, their cellular uptake, and consequently the stimuli responsive release of payload demonstrated the potential of these nanostructures in controlled drug delivery applications.

Liposome-Hydrogel Composites for Controlled Drug Delivery Applications.

Various controlled delivery systems (CDSs) have been developed to overcome the shortcomings of traditional drug formulations (tablets, capsules, syrups, ointments, etc.). Among innovative CDSs, hydrogels and liposomes have shown great promise for clinical applications thanks to their cost-effectiveness, well-known chemistry and synthetic feasibility, biodegradability, biocompatibility and responsiveness to external stimuli. To date, several liposomal- and hydrogel-based products have been approved to treat cancer, as well as fungal and viral infections, hence the integration of liposomes into hydrogels has attracted increasing attention because of the benefit from both of them into a single platform, resulting in a multifunctional drug formulation, which is essential to develop efficient CDSs. This short review aims to present an updated report on the advancements of liposome-hydrogel systems for drug delivery purposes.

Preparation And Characterization of Polyvinyl Alcohol Nanofiber Loaded With Mafenide For Sustain Release

This paper delves into the intricate process of preparing and characterizing Polyvinyl alcohol (PVA) nanofibers loaded with Mafenide to achieve sustained release functionality. The synthesis involves the careful integration of Mafenide, a pharmaceutical agent known for its antimicrobial properties, into PVA nanofibers. This combination holds promise for controlled drug delivery applications. The preparation begins with the electrospinning technique, a method widely employed for creating nanofibrous structures. During this process, the Mafenide is incorporated into the PVA matrix, forming a composite material. The choice of Polyvinyl alcohol as the base material is strategic, given its biocompatibility and excellent film-forming properties. The characterization phase involves a comprehensive analysis of the resulting nanofibers. Techniques such as scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR). are employed to examine the morphology and chemical composition of the nanofibrous system. These analyses provide insights into the structural integrity and the successful incorporation of Mafenide. The study focuses on the sustained release aspect, aiming to understand how the loaded Mafenide interacts within the PVA nanofibers over time. This sustained release mechanism is crucial for pharmaceutical applications, offering prolonged therapeutic effects and minimizing the need for frequent administration. The potential benefits of this research lie in the development of an efficient drug delivery system.

Pivalic acid based N-doped carbon dots for drug delivery and antioxidant behaviour

Heteroatom doped surface engineered carbon dots has immense potential not only in their fluorescent sensing but also in nanocarrier for drug molecules and antioxidant behavior. Herein, we report a one-step thermal coupling synthesis of carbon dots from pivalic acid and naturally abundant gelatin (PGCDs). The as-synthesized PGCDs exhibited excellent colloidal stability, biocompatibility, and antioxidant activity. The surface of PGCDs was further modified with anticancer drug molecules to assess their drug delivery capabilities. The drug-loaded PGCDs demonstrated sustained release profiles, indicating their potential for controlled drug delivery applications. For understanding the drug delivery mechanism, the cumulative release data have been fitted into Weibull and Higuchi model. The PGCDs also showed pH sensitive release behavior where acidic environment has a better control in release profile compared to the alkaline pH. The concentration dependent radical activity shows more than 80% activity at below 1 mg/mL PGCDs concentration. Their low toxicity against live human cell lines could promote this PGCDs as a potential versatile nano-vector biomedical research area.

Advanced 3D Electrospinning "Xspin" System: Fabrication of Bifiber Floating Oral Pharmaceutical Scaffolds for Controlled Drug Delivery.

Electrospinning has become a widely used and efficient method for manufacturing nanofibers from diverse polymers. This study introduces an advanced electrospinning technique, Xspin - a multi-functional 3D printing platform coupled with electrospinning system, integrating a customised 3D printhead, MaGIC - Multi-channeled and Guided Inner Controlling printheads. The Xspin system represents a cutting-edge fusion of electrospinning and 3D printing technologies within the realm of pharmaceutical sciences and biomaterials. This innovative platform excels in the production of novel fiber with various materials and allows for the creation of highly customized fiber structures, a capability hitherto unattainable through conventional electrospinning methodologies. By integrating the benefits of electrospinning with the precision of 3D printing, the Xspin system offers enhanced control over the scaffold morphology and drug release kinetics. Herein, we fabricated a model floating pharmaceutical dosage for the dual delivery of curcumin and ritonavir and thoroughly characterized the product. Fourier transform infrared (FTIR) spectroscopy demonstrated that curcumin chemically reacted with the polymer during the Xspin process. Thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) confirmed the solid-state properties of the active pharmaceutical ingredient after Xspin processing. Scanning electron microscopy (SEM) revealed the surface morphology of the Xspin-produced fibers, confirming the presence of the bifiber structure. To optimize the quality and diameter control of the electrospun fibers, a design of experiment (DoE) approach based on quality by design (QbD) principles was utilized. The bifibers expanded to approximately 10-11 times their original size after freeze-drying and effectively entrapped 87% curcumin and 84% ritonavir. In vitro release studies demonstrated that the Xspin system released 35% more ritonavir than traditional pharmaceutical pills in 2 h, with curcumin showing complete release in pH 1.2 in 5 min, simulating stomach media. Furthermore, the absorption rate of curcumin was controlled by the characteristics of the linked polymer, which enables both drugs to be absorbed at the desired time. Additionally, multivariate statistical analyses (ANOVA, pareto chart, etc.) were conducted to gain better insights and understanding of the results such as discern statistical differences among the studied groups. Overall, the Xspin system shows significant potential for manufacturing nanofiber pharmaceutical dosages with precise drug release capabilities, offering new opportunities for controlled drug delivery applications.

Chitosan based hybrid superabsorbent for controlled drug delivery application.

In the present study, a hybrid chitosan-alginate superabsorbent is prepared using maleic acid as a cross-linker and acrylamide as a grafting agent using the free radical mechanism. The composite hydrogel shows good swelling capacity along with hemocompatibility and biocompatibility and hence it is utilized as a drug delivery device. The characterization techniques including x-ray diffraction, Fourier transform infrared, x-ray photoelectron spectroscopy, and thermal analysis indicate the successful synthesis of stable hydrogel with rich functionalities. Metformin hydrochloride is used as a model drug which is used to treat diabetes. The drug encapsulation is done using the swelling diffusion method after the synthesis of hydrogel. The release of metformin from the drug-loaded hydrogel at physiological pH highlights the role of non-covalent interactions between the drug and hydrogel. In vitro release studies of Metformin from the drug-loaded hydrogel show higher release profiles at intestinal pH (7.4) compared to stomach pH (1.2). The observed cumulative release is 82.71% at pH 7.4 and 45.67% at pH 1.2 after 10 h. Brunauer-Emmett-Teller analysis reveals the effect of surface area, pore size, and pore volume of hydrogel on the drug release. The drug release from the hybrid chitosan-alginate hydrogel is found to be more sustained in comparison to the pure chitosan hydrogel. For the present drug delivery system, the swelling-controlled release is found to be more dominating than the pH-controlled release. The synthesized hydrogel can be successfully employed as a potential drug delivery system for controlled drug delivery.

Red-shifted two-photon-sensitive phenanthridine photocages: synthesis and characterisation.

Herein we describe the rational design, synthesis and photophysical study of a novel class of phenanthridine-based, one- and two-photon sensitive, photoremovable protecting groups with absorption wavelengths extending beyond 400 nm. This design facilitated the development of scaffolds with enhanced uncaging quantum yield, paving the way for broader applications in controlled drug delivery and molecular manipulation.

Poly(lactic acid): Synthesis, modification and applications in controlled drug delivery

Poly(lactic acid) (PLA) is the most promising biodegradable alternative to replace conventionalpetrochemical-based polymers in manufacturing high performance materials. Here we review the main methods to obtain polylactic acid and briefly discuss its functionalization and application in the field of controlled drug release. We conducted a bibliographic search of scientific databases and summarized the results of the research carried out by our group. We show that the most commonly used PLA modifications in drug delivery systems are functionalization with glycolic acid (GA) and polyethylene glycol (PEG) through copolymerization or blending, where the use of compatibilizers is essential for good adhesion. Active vectorization is discussed as its choice depends on the size of the nanoparticle and the type of disease to be treated.

Advances in Biomedical and Environmental Applications of Magnetic Hydrogels

Hydrogels have been the focus of research across disciplines or subject perspectives owing to their distinctive chemical, physical, and mechanical characteristics. Hydrogels have been leveraged for their biocompatibility and attractive adhesion or adsorption behavior. Conventional hydrogels suffer from frequent entrapment due to low controllability, limited responsiveness, and weak actuation properties. Magnetic hydrogels address many of these concerns and offer a rapid magnetic response and precise temporal and spatial control. The structural and functional features of magnetic hydrogels can address overlapping requirements in biomedical and environmental applications. The focus of this review is on the progress made in the use of magnetic hydrogels. Specifically, their applications in controlled drug delivery as contrast agents in magnetic resonance imaging and in the treatment and remediation of wastewater are discussed. The first part of the review delineates strategies for preparing magnetic hydrogels and the advantages of each approach. The second part of the review describes a variety of biomedical and environmental applications for highlighting the convergent functionalities of magnetic hydrogels that are relevant to each domain. The challenges in the use of magnetic hydrogels and prospective applications are also included in the review.

Development of Polymer Membrane using Chitosan/ Hydroxyethyl Cellulose for Controlled Release of Bioactive Agent

The present work describes the fabrication of a polymer membrane using chitosan and hydroxyethyl cellulose by the solvent casting evaporation method. The membranes were loaded with curcumin which is taken as a model bioactive agent for controlled drug delivery applications. The developed membranes were characterized by different techniques such as FTIR, DSC, TGA, XRD and SEM. Curcumin-loaded membranes were tested in in vitro drug release studies in a phosphate buffer solution of pH 7.4 at 37 oC to see how quickly they swelled. The drug-encapsulated membranes have a high release rate of roughly 90% for up to 16 hours. The developed membranes follow a non-Fickian diffusion mechanism with values of ‘n’ ranging from 0.506 to 0.624. The results suggest that our developed membranes warrant further development for drug delivery applications.

Evaluating the in vivo stability of water-soluble PEG-PLA copolymers using FRET imaging

Biodegradable and biocompatible polymer materials with tunable physical properties present a great interest for controlled drug delivery applications. A good example is BEPO®, a clinical-stage in situ-forming depot technology based on the utilization of a blend of poly(ethylene glycol)-b-poly(D,L-lactic acid) (PEG-PLA) diblock and triblock amphiphilic copolymers dissolved in an organic solvent. Once injected, this technology will form a bioresorbable solid polymer depot that will allow the release of a drug from weeks to months. The safety of the final degradation products from this technology, i.e., PEG and lactic acid, is well-documented. However, little information exists about the fate of intermediate degradants, specifically of water-soluble PEG-PLA chains where the molecular weights of the PLA block are short. Herein, we designed a Förster Resonance Energy Transfer (FRET) system for short copolymers, suitable for longitudinal in vivo imaging in the subcutaneous space, allowing to follow the stability of these products. Our results confirm that these species, that might be leaked from BEPO® depots during degradation, are rapidly hydrolyzed in the subcutaneous space of mice, forming approved products by Health Authorities, i.e., PEG and PLA homopolymers and/or lactic acid.

Structural and mechanical properties of folded protein hydrogels with embedded microbubbles.

Globular folded proteins are powerful building blocks to create biomaterials with mechanical robustness and inherent biological functionality. Here we explore their potential as advanced drug delivery scaffolds, by embedding microbubbles (MBs) within a photo-activated, chemically cross-linked bovine serum albumin (BSA) protein network. Using a combination of circular dichroism (CD), rheology, small angle neutron scattering (SANS) and microscopy we determine the nanoscale and mesoscale structure and mechanics of this novel multi-composite system. Optical and confocal microscopy confirms the presence of MBs within the protein hydrogel, their reduced diffusion and their effective rupture using ultrasound, a requirement for burst drug release. CD confirms that the inclusion of MBs does not impact the proportion of folded proteins within the cross-linked protein network. Rheological characterisation demonstrates that the mechanics of the BSA hydrogels is reduced in the presence of MBs. Furthermore, SANS reveals that embedding MBs in the protein hydrogel network results in a smaller number of clusters that are larger in size (∼16.6% reduction in number of clusters, 17.4% increase in cluster size). Taken together, we show that MBs can be successfully embedded within a folded protein network and ruptured upon application of ultrasound. The fundamental insight into the impact of embedded MBs in protein scaffolds at the nanoscale and mesoscale is important in the development of future platforms for targeted and controlled drug delivery applications.