Advanced Delivery Systems Research Articles

Advancements in Vaccine Strategies for Chronic Liver Disease Patients: Navigating Post-COVID Challenges and Opportunities.

This review addresses the vital role of vaccinations in managing patients with chronic liver disease (CLD), especially in the context of the post-COVID-19 landscape. The pandemic has highlighted the unique vulnerabilities of CLD patients, including those awaiting liver transplantation and post-transplant individuals, who face heightened risks of infection due to compromised immune responses. Recent advancements in vaccine technology, such as mRNA platforms, novel adjuvants, and advanced delivery systems, have significantly accelerated vaccine development, enhancing both speed and efficacy. Moreover, the emergence of personalized vaccines, tailored to everyone's unique immunological profile, presents new opportunities, particularly for those with chronic conditions. This review synthesizes the current state of evidence regarding vaccine recommendations for CLD patients, focusing on their response to vaccinations and proposing effective strategies to protect this vulnerable group from vaccine-preventable diseases. It also explores the challenges in implementing these strategies and considers the impact of emerging vaccine delivery systems on improving outcomes for CLD patients. The paper aims to provide nuanced guidance on vaccination in the rapidly evolving healthcare landscape, addressing both technological innovations and comprehensive patient care strategies.

Recent Advances in Intranasal Administration for Brain-Targeting Delivery: A Comprehensive Review of Lipid-Based Nanoparticles and Stimuli-Responsive Gel Formulations.

Addressing disorders related to the central nervous system (CNS) remains a complex challenge because of the presence of the blood-brain barrier (BBB), which restricts the entry of external substances into the brain tissue. Consequently, finding ways to overcome the limited therapeutic effect imposed by the BBB has become a central goal in advancing delivery systems targeted to the brain. In this context, the intranasal route has emerged as a promising solution for delivering treatments directly from the nose to the brain through the olfactory and trigeminal nerve pathways and thus, bypassing the BBB. The use of lipid-based nanoparticles, including nano/microemulsions, liposomes, solid lipid nanoparticles, and nanostructured lipid carriers, has shown promise in enhancing the efficiency of nose-to-brain delivery. These nanoparticles facilitate drug absorption from the nasal membrane. Additionally, the in situ gel (ISG) system has gained attention owing to its ability to extend the retention time of administered formulations within the nasal cavity. When combined with lipid-based nanoparticles, the ISG system creates a synergistic effect, further enhancing the overall effectiveness of brain-targeted delivery strategies. This comprehensive review provides a thorough investigation of intranasal administration. It delves into the strengths and limitations of this specific delivery route by considering the anatomical complexities and influential factors that play a role during dosing. Furthermore, this study introduces strategic approaches for incorporating nanoparticles and ISG delivery within the framework of intranasal applications. Finally, the review provides recent information on approved products and the clinical trial status of products related to intranasal administration, along with the inclusion of quality-by-design-related insights.

Cell-Specific mRNA Therapeutics for Cardiovascular Diseases and Regeneration.

Cardiovascular diseases (CVDs) represent a significant global health burden, demanding innovative therapeutic approaches. In recent years, mRNA therapeutics have emerged as a promising strategy to combat CVDs effectively. Unlike conventional small-molecule drugs, mRNA therapeutics enable the direct modulation of cellular functions by delivering specific mRNA molecules to target cells. This approach offers unprecedented advantages, including the ability to harness endogenous cellular machinery for protein synthesis, thus allowing precise control over gene expression without insertion into the genome. This review summarizes the current status of the potential of cell-specific mRNA therapeutics in the context of cardiovascular diseases. First, it outlines the challenges associated with traditional CVD treatments and emphasizes the need for targeted therapies. Subsequently, it elucidates the underlying principles of mRNA therapeutics and the development of advanced delivery systems to ensure cell-specificity and enhanced efficacy. Notably, innovative delivery methods such as lipid nanoparticles and exosomes have shown promise in improving the targeted delivery of mRNA to cardiac cells, activated fibroblasts, and other relevant cell types. Furthermore, the review highlights the diverse applications of cell-specific mRNA therapeutics in addressing various aspects of cardiovascular diseases, including atherosclerosis, myocardial infarction, heart failure, and arrhythmias. By modulating key regulatory genes involved in cardiomyocyte proliferation, inflammation, angiogenesis, tissue repair, and cell survival, mRNA therapeutics hold the potential to intervene at multiple stages of CVD pathogenesis. Despite its immense potential, this abstract acknowledges the challenges in translating cell-specific mRNA therapeutics from preclinical studies to clinical applications like off-target effects and delivery. In conclusion, cell-specific mRNA therapeutics have emerged as a revolutionary gene therapy approach for CVD, offering targeted interventions with the potential to significantly improve patient outcomes.

Au@16-pH-16/miR-21 mimic nanosystem: An efficient treatment for obesity through browning and thermogenesis induction

Despite the abundance of registered clinical trials worldwide, the availability of effective drugs for obesity treatment is limited due to their associated side effects. Thus, there is growing interest in therapies that stimulate energy expenditure in white adipose tissue. Recently, we demonstrated that the delivery of a miR-21 mimic using JetPEI effectively inhibits weight gain in an obese mouse model by promoting metabolism, browning, and thermogenesis, suggesting the potential of miR-21 mimic as a treatment for obesity. Despite these promising results, the implementation of more advanced delivery system techniques for miR-21 mimic would greatly enhance the advancement of safe and efficient treatment approaches for individuals with obesity in the future. Our objective is to explore whether a new delivery system based on gold nanoparticles and Gemini surfactants (Au@16-ph-16) can replicate the favorable effects of the miR-21 mimic on weight gain, browning, and thermogenesis. We found that dosages as low as 0.2 μg miR-21 mimic /animal significantly inhibited weight gain and induced browning and thermogenic parameters. This was evidenced by the upregulation of specific genes and proteins associated with these processes, as well as the biogenesis of beige adipocytes and mitochondria. Significant increases in miR-21 levels were observed in adipose tissue but not in other tissue types. Our data indicates that Au@16-ph-16 could serve as an effective delivery system for miRNA mimics, suggesting its potential suitability for the development of future clinical treatments against obesity.

Adhesive polydopamine-based photothermal hybrid hydrogel for on-demand lidocaine delivery, effective anti-bacteria, and prolonged local long-lasting analgesia

Considering the astonishing prevalence of localized pain affecting billions of patients worldwide, the development of advanced analgesic formulations or delivery systems to achieve clinical applicability is of great significance. In this study, an integrated PDA-based LiH@PDA@Ag@PAA@Gelatin system was designed for sustained delivery of lidocaine hydrochloride (LiH). By optimizing the preparation process and formulation of the hydrogel, the hydrogel exhibited superior mechanical properties, reversibility, adhesion strength, and self-healing attributes. Moreover, PDA@Ag nanoparticles were evenly dispersed within the hydrogel, and the optimized PDA@Ag@PAA@Gelatin showed a higher photothermal conversion efficiency than that of pure PDA. Importantly, LiH@PDA@Ag@PAA@Gelatin could effectively capture and eradicate bacteria through the synergistic interaction between near-infrared (NIR), PDA, Ag and LiH. In vitro and in vivo tests demonstrated that LiH@PDA@Ag@PAA@Gelatin exhibited higher drug delivery efficiency compared to commercial lidocaine patches. By evaluating the mechanical pain withdrawal threshold of the spared nerve injury (SNI) model in rats, it was proven that LiH@PDA@Ag@PAA@Gelatin enhanced and prolonged the analgesic effect of LiH. Furthermore, LiH@PDA@Ag@PAA@Gelatin induced by NIR possessed excellent on-demand photothermal analgesic ability. Therefore, this study develops a convenient method for preparing localized analgesic hydrogel patches, providing an important step towards advancing PDA-based on-demand pain relief applications.

Tunable theranostics: innovative strategies in combating oral cancer.

This study aims to assess and compare the potential of advanced nano/micro delivery systems, including quantum dots, carbon nanotubes, magnetic nanoparticles, dendrimers, and microneedles, as theranostic platforms for oral cancer. Furthermore, we seek to evaluate their respective advantages and disadvantages over the past decade. A comprehensive literature search was performed using Google Scholar and PubMed, with a focus on articles published between 2013 and 2023. Search queries included the specific advanced delivery system as the primary term, followed by oral cancer as the secondary term (e.g., "quantum dots AND oral cancer," etc.). The advanced delivery platforms exhibited notable diagnostic and therapeutic advantages when compared to conventional techniques or control groups. These benefits encompassed improved tumor detection and visualization, enhanced precision in targeting tumors with reduced harm to neighboring tissues, and improved drug solubility and distribution, leading to enhanced drug absorption and tumor uptake. The findings suggest that advanced nano/micro delivery platforms hold promise for addressing numerous challenges associated with chemotherapy. By enabling precise targeting of cancerous cells, these platforms have the potential to mitigate adverse effects on surrounding healthy tissues, thus encouraging the development of innovative diagnostic and therapeutic strategies for oral cancer.

Advances in delivery systems for CRISPR/Cas-mediated cancer treatment: a focus on viral vectors and extracellular vesicles.

The delivery of CRISPR/Cas systems holds immense potential for revolutionizing cancer treatment, with recent advancements focusing on extracellular vesicles (EVs) and viral vectors. EVs, particularly exosomes, offer promising opportunities for targeted therapy due to their natural cargo transport capabilities. Engineered EVs have shown efficacy in delivering CRISPR/Cas components to tumor cells, resulting in inhibited cancer cell proliferation and enhanced chemotherapy sensitivity. However, challenges such as off-target effects and immune responses remain significant hurdles. Viral vectors, including adeno-associated viruses (AAVs) and adenoviral vectors (AdVs), represent robust delivery platforms for CRISPR/Cas systems. AAVs, known for their safety profile, have already been employed in clinical trials for gene therapy, demonstrating their potential in cancer treatment. AdVs, capable of infecting both dividing and non-dividing cells, offer versatility in CRISPR/Cas delivery for disease modeling and drug discovery. Despite their efficacy, viral vectors present several challenges, including immune responses and off-target effects. Future directions entail refining delivery systems to enhance specificity and minimize adverse effects, heralding personalized and effective CRISPR/Cas-mediated cancer therapies. This article underscores the importance of optimized delivery mechanisms in realizing the full therapeutic potential of CRISPR/Cas technology in oncology. As the field progresses, addressing these challenges will be pivotal for translating CRISPR/Cas-mediated cancer treatments from bench to bedside.

Functionalized extracellular nanovesicles as advanced CRISPR delivery systems.

The clustered regularly interspaced short palindromic repeat (CRISPR) system, an emerging tool for genome editing, has garnered significant public interest for its potential in treating genetic diseases. Despite the rapid advancements in CRISPR technology, the progress in developing effective delivery strategies lags, impeding its clinical application. Extracellular nanovesicles (EVs), either in their endogenous forms or with engineered modifications, have emerged as a promising solution for CRISPR delivery. These EVs offer several advantages, including high biocompatibility, biological permeability, negligible immunogenicity, and straightforward production. Herein, we first summarize various types of functional EVs for CRISPR delivery, such as unmodified, modified, engineered virus-like particles (VLPs), and exosome-liposome hybrid vesicles, and examine their distinct intracellular pathways. Then, we outline the cutting-edge techniques for functionalizing extracellular vesicles, involving producer cell engineering, vesicle engineering, and virus-like particle engineering, emphasizing the diverse CRISPR delivery capabilities of these nanovesicles. Lastly, we address the current challenges and propose rational design strategies for their clinical translation, offering future perspectives on the development of functionalized EVs.

Optimized microfluidic formulation and organic excipients for improved lipid nanoparticle mediated genome editing.

mRNA-based gene editing platforms have tremendous promise in the treatment of genetic diseases. However, for this potential to be realized in vivo, these nucleic acid cargos must be delivered safely and effectively to cells of interest. Ionizable lipid nanoparticles (LNPs), the most clinically advanced non-viral RNA delivery system, have been well-studied for the delivery of mRNA but have not been systematically optimized for the delivery of mRNA-based CRISPR-Cas9 platforms. In this study, we investigated the effect of microfluidic and lipid excipient parameters on LNP gene editing efficacy. Through in vitro screening in liver cells, we discovered distinct trends in delivery based on phospholipid, cholesterol, and lipid-PEG structure in LNP formulations. Combination of top-performing lipid excipients produced an LNP formulation that resulted in 3-fold greater gene editing in vitro and facilitated 3-fold greater reduction of a therapeutically-relevant protein in vivo relative to the unoptimized LNP formulation. Thus, systematic optimization of LNP formulation parameters revealed a novel LNP formulation that has strong potential for delivery of gene editors to the liver to treat metabolic disease.

Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies.

Background: As the overwhelming majority of advanced mRNA delivery systems are preferentially accumulated in the liver, there is an accelerating growth in the demand for the development of non-liver mRNA delivery platforms. Methods: In this study, we prepared cationic lipid-like nanoassemblies through a N-quaternizing strategy. Their physicochemical properties, in vitro mRNA delivery efficiency, and organ tropism in mice were investigated. Results: Introduction of quaternary ammonium groups onto lipid-like nanoassemblies not only enhances their mRNA delivery performance in vitro, but also completely alters their tropism from the spleen to the lung after intravenous administration in mice. Quaternized lipid-like nanoassemblies exhibit ultra-high specificity to the lung and are predominantly taken up by pulmonary immune cells, leading to over 95% of exogenous mRNA translation in the lungs. Such mRNA delivery carriers are stable even after more than one-year storage at ambient temperature. Conclusions: Quaternization provides an alternative method for design of new lung-targeted mRNA delivery systems without incorporation of targeting ligands, which should extend the therapeutic applicability of mRNA to lung diseases.

Microgel delivery systems of functional substances for precision nutrition.

Microgels delivery system have great potential in functional substances encapsulation, protection, release, precise delivery and nutritional intervention. Microgel is a three-dimensional network structure formed by physical or chemical crosslinking of biopolymers, whose characteristics include dispersion and swelling, stable structure, small volume and high specific surface area, and is a special kind of colloid. In this chapter, the common wall materials for preparing food grade microgels, and the main preparation principles, methods, advantages and disadvantages of microgels loaded with functional substances were firstly reviewed. Then the main characteristics of microgel as delivery system, such as deformability, high encapsulation, stimulus-responsive release and targeted delivery, and its potential benefits in intervening chronic diseases were summarized. Finally, the applications of microgel delivery system for functional substance in the field of precision nutrition were discussed. This chapter will help to design of next-generation advanced targeting microgel delivery system, and realize precision nutrition intervention of food functional substances on body health.

Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug.

Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration normally remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., 1215 formulations). Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevented degradation of drug. Moreover, the high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex®.

Mechanism, applications and of mRNA vaccines

In recent years, infectious diseases such as novel coronavirus pneumonia, influenza, and tuberculosis have brought great social and economic burdens to the world. Vaccination is the most effective and economical intervention to control the spread of infectious diseases, save lives and protect people's health. mRNA vaccine is expected to be a new type of infectious disease vaccine. Compared with traditional vaccines, mRNA vaccines have many advantages, such as high efficiency, safety, short production cycle, low cost, etc. However, the stability of mRNA vaccines is poor. However, mRNA vaccines have poor stability and low delivery efficiency, and their clinical applications are greatly restricted. Therefore, current and future research focuses on the design of advanced and tolerable delivery systems to improve the efficiency of antigen expression and presentation, as well as the optimization of mRNA structure to prolong and control the duration of expression, under the premise of ensuring the safety of vaccines. This review summarizes the history, classification, principles and mechanisms of mRNA vaccines, and briefly discusses the current challenges and future directions for developing mRNA vaccines for different diseases.

Essential Oils in Cervical Cancer: Narrative Review on Current Insights and Future Prospects.

Cervical cancer is a prevalent and often devastating disease affecting women worldwide. Traditional treatment modalities such as surgery, chemotherapy, and radiation therapy have significantly improved survival rates, but they are often accompanied by side effects and challenges that can impact a patient's quality of life. In recent years, the integration of essential oils into the management of cervical cancer has gained attention. This review provides an in-depth exploration of the role of various essential oils in cervical cancer, offering insights into their potential benefits and the existing body of research. The review also delves into future directions and challenges in this emerging field, emphasizing promising research areas and advanced delivery systems. The encapsulation of essential oils with solid lipid nanoparticles, nanoemulsification of essential oils, or the combination of essential oils with conventional treatments showed promising results by increasing the anticancer properties of essential oils. As the use of essential oils in cervical cancer treatment or management evolves, this review aims to provide a comprehensive perspective, balancing the potential of these natural remedies with the challenges and considerations that need to be addressed.

Three-dimensional hydrogel with human Wharton jelly-derived mesenchymal stem cells towards nucleus pulposus niche.

Introduction: A regenerative strategy employing extracellular matrix (ECM)-based biomaterials and stem cells provide a better approach to mimicking the three-dimensional (3D) microenvironment of intervertebral disc for endogenous tissue regeneration. However, there is currently limited understanding regarding the human Wharton Jelly derived-mesenchymal stem cells (hWJ-MSCs) towards nucleus pulposus (NP)-like cells. Our study focused on the development of 3D bioengineered hydrogel based on the predominant ECM of native NP, including type II collagen (COLII) and hyaluronic acid (HA), which aims to tailor the needs of the microenvironment in NP. Methods: We have fabricated a 3D hydrogel using from COLII enriched with HA by varying the biomacromolecule concentration and characterised it for degradation, stability and swelling properties. The WJ-MSC was then encapsulated in the hydrogel system to guide the cell differentiation into NP-like cells. Results: We successfully fabricated COLII hydrogel (2mg/ml) and HA 10mg/ml at a weight ratio of HA and COLII at 1:9 and 4.5:9, and both hydrogels physically maintained their 3D sphere-shaped structure after complete gelation. The higher composition of HA in the hydrogel system indicated a higher water intake capacity in the hydrogel with a higher amount of HA. All hydrogels showed over 60% hydrolytic stability over a month. The hydrogel showed an increase in degradation on day 14. The hWJ-MSCs encapsulated in hydrogel showed a round morphology shape that was homogenously distributed within the hydrogel of both groups. The viability study indicated a higher cell growth of hWJ-MSCs encapsulated in all hydrogel groups until day 14. Discussion: Overall, our findings demonstrate that HA/COLII hydrogel provides an optimal swelling capacity, stability, degradability, and non-cytotoxic, thus mimics the NP microenvironment in guiding hWJ-MSCs towards NP phenotype, which is potentially used as an advanced cell delivery system for intervertebral disc regeneration.

Protein Nanotubes as Advanced Material Platforms and Delivery Systems.

Protein nanotubes (PNTs) as state-of-the-art nanocarriers are promising for various potential applications both in the food and pharmaceutical industries. Derived fromedible starting sources like α-lactalbumin, lysozyme, and ovalbumin, PNTs bear properties of biocompatibility and biodegradability. Their large specific surface area and hydrophobic core facilitate chemical modification and loading of bioactive substances, respectively. Moreover, their enhanced permeability and penetration ability across biological barriers such as intestinal mucus, extracellular matrix, and thrombus clot, make it promising platforms for health-related applications. Most importantly, their simple preparation processes enable large-scale production, supporting applications in the biomedical and nanotechnological fields. Understanding the self-assembly principles is crucial for controlling their morphology, size, and shape, and thus providesthe ground to a multitude of applications. Here, the current state-of-the-art of PNTs including their building materials, physicochemical properties, and self-assembly mechanisms are comprehensively reviewed. The advantages and limitations, as well as challenges and prospects for their successful applications in biomaterial and pharmaceutical sectors are then discussed and highlighted. Potential cytotoxicity of PNTs and the need of regulations as critical factors for enabling in vivo applications are also highlighted. In the end, a brief summary and future prospects for PNTs as advanced platforms and delivery systems are included.

Flexible Zenker's Per-oral Endoscopic Myotomy

Zenker's diverticulum is a pulsion-type pseudodiverticulum of the pharyngoesophageal segment. Endoscopic surgery is primarily directed at dividing the common wall between the esophagus and diverticulum. Rigid exposure with diverticuloscopes have allowed for common wall division with staplers, lasers, and advanced energy sealers, however not all patients can be successfully treated with rigid instrumentation. As a result, flexible endoscopic surgery provides another option for patients. This technique employs various instrumentation through the working channel of a gastroscope to not only divide the common wall but seal the incision, which if done appropriately, results in a symptom resolution with complication rates comparable to rigid techniques. Flexible endoscopic surgery requires the surgeon to perform technically challenging submucosal dissection through a gastroscope as well as possess expertise with advanced energy delivery systems and instrumentation. However, with time, surgeons can build these skills to offer the breadth of surgical options tailored to the individual patient.

Nanogel Particles Based on Modified Nucleosides and Oligosaccharides as Advanced Delivery System.

This work addresses the challenge of delivering bioactive molecules by designing biocompatible nanogel particles (NGPs) utilizing rationally modified nature-sourced building blocks: capryl-oligochitosan and oxidized inosine. Capryl substituents endowed the resultant NGPs with membrane-penetration capabilities, while purine-containing inosine allowed H-bond/π-π/π-cation interactions. The prepared NGPs were complexed with carboxyfluorescein-labeled single-stranded oligonucleotide (FAM-oligo) and DsRed-encoding plasmid DNA. The successful delivery of FAM-oligo to the cell cytoplasm of the Nicotiana benthamiana plant was observed. Alexa 555-labeled bovine serum albumin (Alexa 555-BSA) was also efficiently encapsulated and delivered to the plant. In addition to delivering FAM-oligo and Alexa 555-BSA separately, NGPs also successfully co-delivered both biomolecules to the plant. Finally, NGPs successfully encapsulated the drug amphotericin B and reduced its toxicity while maintaining its efficacy. The presented findings suggest that NGPs may become a promising platform for the advanced delivery of bioactive molecules in various applications.

Controlled release of therapeutic antibody using hydrolytically degradable microgels.

Monoclonal antibodies have gained significant interest as potential therapeutics for treating various diseases. However, these therapies are not always effective due to poor treatment compliance associated with multiple administrations and drug resistance. Thus, there is a growing interest in developing advanced monoclonal antibody delivery systems that can customize pharmacokinetics to enhance therapeutic outcomes. This work aimed to engineer hydrolytic 4-arm PEG maleimide (PEG-4MAL) microgels for the controlled delivery of therapeutic antibodies, specifically anti-angiogenic bevacizumab, to overcome the limitations of current monoclonal antibody therapies. Through a PEGylation reaction with a thiol-terminated PEG linker, the antibody was covalently conjugated to the macromer backbone before microgel synthesis. The PEGylation reaction was simple, effective, and did not affect antibody bioactivity. Antibody release kinetics was tuned by changing the concentration of the hydrolytic linker (0-2 mM) and/or PEG-4MAL:protein molar ratio (1000:1, 2000:1, and 5000:1) in the macromer precursor solution during microgel fabrication. The bioactivity of the released antibody was assessed on human umbilical endothelial vascular cells (HUVEC), demonstrating that extracts from hydrolytic microgels reduced cell proliferation over time. Collectively, this study demonstrates the development of highly tunable delivery platform based on degradable PEG-4MAL microgels that can be adapted for therapeutic antibody-controlled release.

Innovative Insights for Establishing a Synbiotic Relationship with Bacillus coagulans: Viability, Bioactivity, and In Vitro-Simulated Gastrointestinal Digestion.

This study investigates the use of encapsulating agents for establishing a synbiotic relationship with Bacillus coagulans (TISTR 1447). Various ratios of wall materials, such as skim milk powder, maltodextrin, and cellulose acetate phthalate (represented as SMC1, SMC3, SMC5, and SMC7), were examined. In all formulations, 5% inulin was included as a prebiotic. The research assessed their impact on cell viability and bioactive properties during both the spray-drying process and in vitro gastrointestinal digestion. The results demonstrate that these encapsulating agents efficiently protect B. coagulans spores during the spray-drying process, resulting in spore viability exceeding 6 log CFU/g. Notably, SMC5 and SMC7 displayed the highest spore viability values. Moreover, SMC5 showcased the most notable antioxidant activity, encompassing DPPH, hydroxy radical, and superoxide radical scavenging, as well as significant antidiabetic effects via the inhibition of α-amylase and α-glucosidase. Furthermore, during the simulated gastrointestinal digestion, both SMC5 and SMC7 exhibited a slight reduction in spore viability over the 6 h simulation. Consequently, SMC5 was identified as the optimal condition for synbiotic production, offering protection to B. coagulans spores during microencapsulation and gastrointestinal digestion while maintaining bioactive properties post-encapsulation. Synbiotic microcapsules containing SMC5 showcased a remarkable positive impact, suggesting its potential as an advanced food delivery system and a functional ingredient for various food products.