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Hypoxia has evolved from being considered a mere byproduct of the tumor microenvironment to a recognized active contributor to tumor development, invasion, and metastasis, highlighting the importance of targeting hypoxia as a therapeutic strategy to improve oncological outcomes. In this study, we developed a straightforward drug delivery system that responds to hypoxic conditions using the organic solvent volatilization technique. We synthesized an amphiphilic polymer, poly-(ethylene glycol)-phthalic acid-nitroimidazole (PEG–PA-NI), by linking hydrophilic poly-(ethylene glycol) (PEG) to nitroimidazole acyl through an amidation reaction. This polymer was then used to create hypoxia-responsive nanoscale micelles (HRM NPs), which were loaded with the chemotherapeutic drug doxorubicin (DOX), and the resulting construct was termed hypoxia-responsive nanoplatforms (HRM@DOX NPs). Within the hypoxic and reducing tumor microenvironment, the hydrophobic compound 2-nitroimidazole undergoes conversion into its hydrophilic counterpart, 2-aminoimidazole, which is catalyzed by the overexpressed nitroreductase enzyme, leading to the disruption of the micelle structure and the accelerated release of the drug. This enzymatic transformation relies on the cofactor-reduced nicotinamide adenine dinucleotide phosphate (NADPH). Importantly, this conversion also disrupts the redox balance within the cancer cells, facilitating tumor cell apoptosis. Through experiments measuring changes in oxidized nicotinamide adenine dinucleotide phosphate hydrogen (NADP+) and glutathione (GSH) content in tumor tissues of mice, we demonstrated that HRM NPs could disrupt the redox balance within tumor cells under hypoxic conditions and enhance the therapeutic effects of chemotherapeutic drugs. This innovative hypoxia-responsive nanoplatform not only enhances drug release under hypoxic conditions but also induces a disruption in the redox balance specific to cancer cells, thereby promoting apoptosis. The utilization of hypoxia-sensitive polymers presents a promising avenue for advancing the effectiveness of cancer treatments, ensuring targeted therapeutic responses with minimized impact on healthy tissues. [ABSTRACT FROM AUTHOR]

In order to overcome the side effects of pancreatic transplantation and insulin injection treatment for type I diabetes, we established a drug delivery system employing nanoparticle embedded microcapsules (NEMs). The system co-encapsulated chitosan nanoparticles with γ-aminobutyric acid and β-TC-6 cells for combined drug and cell therapy in diabetes mellitus (DM). The NEMs, which were formed via high-voltage electrostatic method, had an excellent sphericity with a smooth surface. The average size NEM was 245.52 ± 22.00 μm, which indicated a good size for cell encapsulation. Haemolysis rate of NEMs at concentrations of 100, 200 or 300 mg/mL were all below 5%. Relative viability rates of L929 cells with the same concentrations at 24, 48 or 72 h were all above 80%. We implanted bioactive NEMs into type 1 DM mice to evaluate the effect of the combined therapy. The level of blood glucose in the group receiving the combined therapy decreased during the first 2 weeks of treatment. During the next week, the level of blood glucose stayed in a safe range. Body weight continuously increased during the postoperative period after combined therapy group. Oral glucose tolerance test (OGTT) performed after 24 d showed that the level of blood glucose combined therapy reached the maximum peak of 13.04 mmol/L, lower than 16.56 mmol/L for the cell therapy group. This primary study indicated that microencapsulation technology and combined therapy are promising for the treatment of type I diabetes mellitus. [ABSTRACT FROM AUTHOR]

Herein, we fabricated the novel drug delivery system based on the self‐assembly of two polyelectrolytes, poly‐allylamine hydrochloride (PAH) and fucoidan, as the polycation and polyanion, respectively, under mild conditions for cancer therapeutics. Furthermore, the designed polyelectrolyte complex nanoparticles as well as the methotrexate (MTX) disodium salt‐loaded composites were systematically characterized using various techniques. The MTX loading in the nanoparticles was confirmed by zeta potential values that changed from −36.2 ± 2.2 to −28.3 ± 3.1 mV at a loading amount of 13.3 ± 1.2%. Furthermore, the obtained eventual particle sizes of nanoparticles were various with different concentrations and ratios of polyelectrolytes. The particle size also has increased from 130 ± 2.6 to 162.9 ± 2.3 nm after loading MTX. The drug release investigations in vitro at a pH value of 6.0 (acid environment) showed that the release of MTX was sustained in the conditions provided. Finally, we investigated the anticancer efficacy of MTX‐loaded nanoparticles on MCF‐7 cells and HeLa cells and the satisfactory results were obtained. Together, these self‐assembled PAH/fucoidan nanoparticles with sustained drug release property will become the promising delivery system for cancer therapeutics. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 339–347, 2019. [ABSTRACT FROM AUTHOR]

To improve the efficacy and reduce the systemic toxicity of the diabetes mellitus, herewith, we developed a novel microparticles-embedded microcapsules (MEMs) system, synthesized from calcium alginate/chitosan (Ca-Alg/CS), by emulsion gelation using a high voltage electrostatic droplet generator. In our study, we selected two antidiabetic drugs insulin (INS) and metformin (MET) as model drugs to investigate different spatial distribution appropriate of MEMs system. Characterization based on particle size and morphology, encapsulation efficiency and drug loading, as well as drug delivery properties were carried out on the MEMs system. Typical multi-chamber structure was shown by SEM and the optical spectra. The average diameters of microparticles and Ca-Alg/CS MEMs were 2100 nm and 410 μm, respectively. Insulin and MET were embedded into MEMs via electrostatic reaction according to FT-IR spectra. Moreover, drug loading and encapsulation efficiency of INS were higher than that of MET in this system when drugs were loaded alone or together. More importantly, this system has potential for orderly drug release and well sustained release when MET in the inner and INS in the outer space could be applied as a combination therapy for diabetes. The obtained in vivo experimental data on diabetes rats has shown that the designed MEMs system resulted in a higher hypoglycemic effect within add-on therapy. [ABSTRACT FROM AUTHOR]

Add-on drugs, often called as synergistic therapy, for diabetes have been comparatively more promising as they can reduce the systemic adverse effects resulted during respective monotherapy [metformin (MET)/insulin (INS)]. Herewith, we formulated a multivesicular liposome microparticles-embedded Ca-Alg/chitosan microcapsules (MVL-Ca-Alg/CS MEMs) system by a double-emulsion method using a high voltage electrostatic droplet generator. Physical characterization of the designed formulation was elucidated based on particle size and distribution, drug loading and encapsulation efficiency, drug delivery properties, and pharmacodynamic evaluation. The multivesicular liposomes microparticles (MVLs MPs) and MVL-Ca-Alg/CS MEMs have shown good sphericity and dispersion, and the average diameters were 37 and 491 µm, respectively. The confocal laser scanning microscopic observations demonstrated that fluorescein isothiocyanate-conjugated INS is uniformly dispersed in MVLs MPs, predominantly within the lumen of the polycystic liposome. This multicomponent system possessing INS in the inner space and MET at the outer space resulted in orderly and sustained drug release patterns. Furthermore, the obtained in vivo experimental data have shown that the designed MEMs system resulted in significantly higher hypoglycemic effect compared to pure INS, demonstrating that our multicomponent design has an enormous potential for treating diabetes. [ABSTRACT FROM AUTHOR]

In order to improve alginate microbead stability and further broaden the application of alginate in biomaterials, a new biomaterial, ALG-g-Lys, was prepared and its possibility as a novel drug carrier investigated. The carrier exhibited a sustained release property and preserved activity with no initial burst release, and interestingly, GP-crosslinked ALG-g-Lys microspheres showed obvious fluorescence properties, which showed promising potential for the future drug delivery systems. [ABSTRACT FROM AUTHOR]

Cell encapsulation in hydrogels has been extensively used in cytotherapy, regenerative medicine, 3D cell culture, and tissue engineering. Herein, we fabricated microencapsulated cells through microcapsules loaded with C5.18 chondrocytes alginate/chitosan prepared by a high-voltage electrostatic method. Under optimized conditions, microencapsulated cells presented uniform size distribution, good sphericity, and a smooth surface with different cell densities. The particle size distribution was determined at 150–280 μm, with an average particle diameter of 220 μm. The microencapsulated cells were cultured under static, shaking, and 3D micro-gravity conditions with or without bFGF (basic fibroblast growth factor) treatment. The quantified detection (cell proliferation detection and glycosaminoglycan (GAG)/type II collagen (Col-II)) content was respectively determined by cell counting kit-8 assay (CCK-8) and dimethylmethylene blue (DMB)/Col-II secretion determination) and qualitative detection (acridine orange/ethidium bromide, hematoxylin-eosin, alcian blue, safranin-O, and immunohistochemistry staining) of these microencapsulated cells were evaluated. Results showed that microencapsulated C5.18 cells under three-dimensional microgravity conditions promoted cells to form large cell aggregates within 20 days by using bFGF, which provided the possibility for cartilage tissue constructs in vitro. It could be found from the cell viability (cell proliferation) and synthesis (content of GAG and Col-II) results that microencapsulated cells had a better cell proliferation under 3D micro-gravity conditions using bFGF than under 2D conditions (including static and shaking conditions). We anticipate that these results will be a benefit for the design and construction of cartilage regeneration in future tissue engineering applications. [ABSTRACT FROM AUTHOR]

To solve the problem of tumor multidrug resistance in cancer therapy, a new drug delivery system of genipin-cross-linked iron (III) oxide/polyetherimide nanoparticles was used to load doxorubicin and small interfering RNA for combined cancer therapy. The results showed that the drug loading and encapsulation efficiency of doxorubicin could reach 45.39% and 52.18%, respectively. Doxorubicin released from iron (III) oxide-polyetherimide-doxorubicin is about 40% in the first day and 95% in 14 days. When loading doxorubicin and small interfering RNA, small interfering RNA could be absorbed completely. Besides, small interfering RNA could strengthen the anticancer effect when iron (III) oxide-polyetherimide-doxorubicin/small interfering RNA was used for in vitro HeLa cell combined treatment, and the effect of combination group was better than that of the group with doxorubicin alone. In addition, the toxicity of iron (III) oxide-polyetherimide was low when examined by the Alamar Blue assay. Therefore, our results reveal that this new system has potential applications in the future drug combination therapy, especially in the combined targeting drug delivery field. [ABSTRACT FROM AUTHOR]

Cartilage tissue engineering through culturing chondrocytes in 3D porous scaffolds has potential for the repair of articular cartilage defects. To promote cell distribution in the scaffold, a novel construction method was proposed based on artificial cells and matrix-shaping. Results showed that the construct had better proliferation and ECM secretion with bFGF. Cells had the best proliferation, largest GAG and type II collagen content on day 10 in the 2D condition without bFGF, while these were enhanced by bFGF to day 15. Under 3D conditions, the highest proliferation and GAG content were on day 15 in bFGF-free medium while these two values were improved by bFGF, with the highest appearing on day 20. In conclusion, this construction method is efficient and provides a new and promising approach to cartilage regeneration. [ABSTRACT FROM AUTHOR]

Abstract: The strategy to construct a novel drug delivery system of nanoparticle embedded microcapsules (NEMs) is reported in this work. The Chitosan/Alginate Nanoparticle Embedded Microcapsules (CS/Alg NEMs) have been successfully prepared by emulsion-gelation and high-voltage electrostatic droplet generator. The drug release behavior in vitro of the NEMs was studied, using Capecitabine (CAP) and γ-globulin as model drugs. The results demonstrated that the NEMs could control the drugs'' release rate significantly, whether it is a small-molecular drug or peptide and protein. Also, the results indicated that the co-loading drugs exhibited an orderly release property. The NEMs exhibited a great potential for application in drug delivery for multi-functions and sustained release. [Copyright &y& Elsevier]

• Nanoparticles coated with red blood cell membranes (RmGIB NPs) were developed. • RmGIB NPs loaded indocyanine green and a gambogic acid. • RmGIB NPs could prolong long-term circulation in vivo. • RmGIB NPs could provide synergistic chemo-photothermal therapy for tumor. Recently, the fabrication of nanotechnology-based co-delivery systems has garnered enormous interest for efficacious cancer therapy. However, these systems still face certain challenges such as codelivery of drugs with different chemistries, inadequate loading efficiency, immune rejection resulting in rapid clearance and substantially poor bioavailability in vivo. To address the challenges, we have developed a biomimetic and stable design based on bovine serum albumin (BSA) nanoparticles that are encapsulated with a hydrophilic photothermal agent, indocyanine green (ICG), as well as a hydrophobic agent, gambogic acid (GA), via the desolvation method. Furthermore, these nanoconstructs have been coated with the red blood cell membranes (RBCm), which exhibit pronounced long-term circulation in addition to avoiding premature leakage of drugs. RBCm-coated BSA nanoparticles show a higher affinity towards both GA and ICG (RmGIB NPs), resulting in high loading efficiencies of 24.3 ± 1.2 % and 25.0 ± 1.2 %, respectively. Moreover, the bio-efficacy investigations of these biomimetic constructs (RmGIB NPs) in cells in vitro as well as in tumor-bearing mice in vivo confirm augmented inhibition, demonstrating potential synergistic chemo-photothermal therapeutic efficacy. Altogether, we provide an efficient delivery platform for designing and constructing BSA nanovehicles toward synergistic and effective co-delivery of therapeutics. [ABSTRACT FROM AUTHOR]