bims-livmat 2026-06-14 papers

Ann Pharm Fr. 2026 Jun 09. pii: S0003-4509(26)00097-0. [Epub ahead of print]

Pharmaco-microdynamics (PMD): Redefining Dose, Exposure, and Control for Living Drug Carriers.

Mishel Abdullah, K Jayadevan, Amalkrishnan Therayil, Nivetha Kumaraguruparan, P K V Kavyasree, P Dilna, Alhan Faiza.

Living drug delivery systems including probiotics, engineered microbial therapeutics, and live biotherapeutic products represent a rapidly emerging therapeutic modality whose behavior fundamentally diverges from the assumptions underlying classical pharmacokinetics and pharmacodynamics (PK/PD). Unlike chemically defined, non-replicating drugs, living therapeutics persist, replicate, adapt, and generate bioactive molecules in situ, such that therapeutic exposure is not externally imposed but biologically generated over time. As a result, administered dose functions only as an initiating condition, while realized exposure emerges from population dynamics, ecological establishment, spatial localization, and regulated functional output. These properties render concentration-based PK/PD frameworks insufficient for predicting efficacy, safety, and controllability of living drug carriers. We introduce pharmaco-microdynamics (PMD) as a quantitative delivery-science framework designed to define, measure, and control exposure for living therapeutics. PMD is operationalized through a set of formal metrics including the functional exposure integral (F-AUC), colonization efficiency (CE), residence-time-weighted activity (RTWA), effective functional concentration (EFC50), and the genetic stability index (GSI)that serve as living-system analogues of AUC, bioavailability, mean residence time, EC50, and product-identity specifications. PMD reconceptualizes exposure as a time-integrated biological process governed by four interdependent axes: population kinetics, functional output kinetics, spatial pharmacology, and evolutionary dynamics. By integrating principles from pharmacology, microbial ecology, synthetic biology, biomaterials science, and systems modeling, PMD provides an operational vocabulary for translating adaptive biological agents into predictable and engineerable delivery systems. We further delineate PMD from adjacent frameworks such as quantitative systems pharmacology (QSP) and ecological microbiome modeling, and critically discuss boundary conditions under which classical PK/PD remains applicable to non-replicating or transient microbial interventions. This review critically examines the limitations of classical PK/PD in modeling living drug carriers, formalizes the core principles of PMD, and illustrates them through three quantitative case studies: SYNB1618 for phenylketonuria, synchronized-lysis bacterial tumor therapies, and fecal microbiota transplantation for recurrent Clostridioides difficile infection. Regulatory and clinical implications are addressed, emphasizing the need to shift from dose- and concentration-centric evaluation toward functional biomarkers, persistence metrics, and model-informed assessment of biological activity. Collectively, pharmaco-microdynamics establishes a unifying conceptual and quantitative foundation for the rational development of living medicines.

Keywords: bactéries ingénierées; biomaterials; biomatériaux; biothérapeutiques vivants; digital twins; engineered bacteria; exposure–response; jumeaux numériques; living biotherapeutics; microbiome pharmacology; pharmaco-microdynamics; pharmaco-microdynamique; pharmacologie des systèmes quantitatifs; pharmacologie du microbiome; quantitative systems pharmacology; relation exposition–réponse

DOI: https://doi.org/10.1016/j.pharma.2026.06.002

Polym Sci Technol. 2025 Aug 26. 1(6): 503-528

Bacterial Systems as a Precision Delivery Platform of Therapeutic Peptides for Cancer Therapy.

Jinyuan Liu, Guizhi Shen, Xuehai Yan.

In recent years, peptide-based therapies have gained remarkable attention as promising tools for cancer treatment, offering notable advantages in specificity, modifiability, and reduced systemic toxicity. Various peptide classesincluding cell-penetrating, tumor-homing, pro-apoptotic, and immune-modulating peptideshave shown appreciable efficacy in selectively targeting cancer cells and modulating immune responses against tumors. Despite this potential, peptide therapies face significant challenges, such as susceptibility to rapid degradation, limited bioavailability, and inadequate accumulation within tumors. To address these issues, bacterial systems have emerged as innovative peptide delivery platforms, improving peptide stability, enhancing localized concentrations, and enabling controlled release directly at tumor sites. This review explores the synergistic potential of therapeutic peptides combined with bacterial delivery systems, with a focus on methods such as bacterial lysis for peptide release, secretion pathways, and peptide surface display. By harnessing the tumor-targeting properties and secretion capabilities of bacteria, these integrated approaches offer promising solutions to overcome the inherent limitations of peptide therapies, positioning them as advanced tools in precision oncology.

Keywords: bacterial secretion; bacterial surface display; cancer therapy; direct bacterial lysis; engineered bacterial; therapeutic peptides

DOI: https://doi.org/10.1021/polymscitech.4c00026

World J Microbiol Biotechnol. 2026 Jun 10. pii: 341. [Epub ahead of print]42(7):

Effect of protein-carbohydrate wall systems on viability and stability of freeze-dried probiotic microcapsules.

Sparsh Sumnirom Subba, Araveti Sumana.

Probiotic applications are often limited by poor survival during processing and storage, highlighting the need for effective protective encapsulation systems. This study comparatively evaluated the influence of protein-carbohydrate wall material systems on the structural stability and viability of freeze-dried microcapsules. Microcapsules were designed using maltodextrin (MD), skim milk powder (SMP), and gum arabic (GA) in single, binary, and ternary combinations to individually encapsulate four probiotic strains (Lactiplantibacillus plantarum, Limosilactobacillus fermentum, Lactobacillus acidophilus, and Bifidobacterium breve). Encapsulation efficiency, cell viability, physicochemical properties (moisture content, water activity, bulk density, and color), and structural characteristics (scanning electron microscopy, dynamic light scattering, zeta potential, X-ray diffraction, thermogravimetric analysis, and Fourier-transform infrared spectroscopy) were evaluated. Compared with single- and binary-wall systems, the ternary MD:SMP:GA formulation demonstrated improved encapsulation efficiency and maintained post-lyophilization viability up to 9.25 log CFU/mL. Wall material composition largely influenced microcapsule structure and probiotic survival, with only minor strain-dependent variability observed. Structural analyses indicated that MD:SMP:GA promoted the formation of uniform amorphous microstructures stabilized through hydrogen-bonding interactions and electrostatic effects, creating a protective microenvironment that limited molecular mobility and preserved cellular integrity during freeze-drying. These findings provide mechanistic insight into protein-carbohydrate interactions influencing freeze-dried microencapsulation and demonstrate the potential of ternary MD:SMP:GA systems for improving probiotic stability in functional food and nutraceutical applications.

Keywords: Freeze-drying; Probiotic microencapsulation; Probiotic viability; Protein-carbohydrate interactions; Wall material systems

DOI: https://doi.org/10.1007/s11274-026-05069-8

J Control Release. 2026 Jun 06. pii: S0168-3659(26)00485-2. [Epub ahead of print]396 115082

Delivering living medicines with polysaccharide derivatives for disease treatment.

Qianying Huang, Binglin Ye, Huang Yang, Zhengwei Mao, Weili Wang.

Living medicines represent a revolutionary approach to modern therapeutics, but their effective delivery and in vivo functional maintenance pose significant challenges. Polysaccharide derivatives have emerged as ideal materials for the construction of advanced delivery systems owing to their exceptional biocompatibility, ECM-mimetic microenvironment and mechanically tunable properties. This review systematically analyses the applications of polysaccharide derivatives in live medicine delivery, elucidating their chemical modification strategies, design principles of delivery systems, and disease-specific applications. We focused on the latest advances in polysaccharide-based delivery systems for inflammatory bowel disease, cancer, central nervous system disorders, and tissue regeneration, while addressing the challenges in clinical translation and future directions. In summary, this review thus bridges fundamental material design with translational goals, offering guidance for developing effective polysaccharide-based delivery systems for living medicines.

Keywords: Biocompatibility; Drug delivery; Engineered cells; Living medicines; Polysaccharide derivatives; Targeted therapy

DOI: https://doi.org/10.1016/j.jconrel.2026.115082