Microparticle-based Delivery Systems Research Articles

Spinning gold: Unraveling the bioaccessibility and bioavailability of Pitanga’s carotenoid microfibers

The design and development of nanoparticle- and microparticle-based delivery systems incorporating carotenoids into carrier materials offers multiple advantages, including enhancing the bio-efficacy of these compounds due to improving their bioaccessibility and bioavailability. This study introduced pitanga saponified carotenoid extract (PSCE) and pitanga non-saponified carotenoid extract (PSCE) in a 12 % zein/1 %PEO solution and electrospun for fiber production. Then, the fibers were characterized, and their bioaccessibility and bioavailability were also evaluated. The average mean diameter of carotenoid non-saponified microfiber (CNSM) and saponified (CSM) was 5.76 ± 1.7 μm and 4.92 ± 1.4 μm, respectively, indicating that the saponification process reduces the viscosity of the solution resulting in the development of finer microfibers. Carotenoid encapsulation efficiency ranged between 10.3 % and 8.43 % for saponified and non-saponified extracts, respectively. Surprisingly, no carotenoid release was detected from both microfibers after 72 h. Carotenoid bioaccessibility was higher in pitanga pulp compared to both microfibers. The xanthophylls showed higher bioavailability in pitanga pulp. The study’s results suggest that the microfibers’ structure significantly influenced carotenoid release and cellular absorption more than the chemical structure of carotenoids themselves.

Sustained adenosine release: Revealing its impact on osteogenic signalling pathways of human mesenchymal stromal cells

Non-healing fractures, a global health concern arising from trauma, osteoporosis, and tumours, can lead to severe disabilities. Adenosine, integral to cellular energy metabolism, gains prominence in bone regeneration via adenosine A2B receptor activation. This study introduces a controlled-release system for localized adenosine delivery, fostering human mesenchymal stromal cell (hMSC) differentiation into functional bone cells. The study investigates how the ratio of lactic acid to glycolic acid in microparticles can influence adenosine release and explores the downstream effects on gene expression and metabolic profiles of osteogenic differentiation in hMSCs cultured in growth and osteoinductive media. Insights into adenosine-modulated signalling pathways during MSC differentiation, with osteogenic factors, provide a comprehensive understanding of the pathways involved. Analysing gene expression and metabolic profiles unravels adenosine's regulatory mechanisms in MSC differentiation. Sustained adenosine release from microparticles induces mineralization, synergizing with osteogenic media supplements, showcasing the potential of adenosine for treating critical bone defects and metabolic disorders. This study highlights the efficacy of a polymeric microparticle-based delivery system, offering novel strategies for bone repair. Unveiling adenosine's roles and associated signalling pathways advances our comprehension of molecular mechanisms steering bone regeneration, propelling innovative biomaterial, combined with metabolites, approaches for clinical use.

Self-Reporting Photoluminescent Porous Silicon Microparticles for Drug Delivery.

A porous Si (pSi) microparticle-based delivery system is investigated, and the intrinsic luminescence from the particles is employed as a probe to monitor the release of a model protein payload, bovine serum albumin (BSA). The microparticles consist of a core Si skeleton surrounded by a SiO2 shell. Two types of pSi are tested, one with smaller (10 nm) pores and the other with larger (20 nm) pores. The larger pore material yields a higher mass loading of BSA (3 vs 20%). Two different methods are used to load BSA into these nanostructures: the first involves loading by electrostatic physisorption, and the second involves trapping of BSA in the pSi matrix by local precipitation of magnesium silicate. Protein release from the former system is characterized by a burst release, whereas in the latter system, release is controlled by dissolution of the pSi/magnesium silicate matrix. The protein release characteristics are studied under accelerated (0.1 M aqueous KOH, 21 °C) and physiologically relevant (phosphate-buffered saline, pH 7.4, 37 °C) conditions, and the near-infrared photoluminescence signal from the pSi skeleton is monitored as a function of time and correlated with protein release and silicon dissolution. The thickness of the Si core and the SiO2 shell are systematically varied, and it is found that the luminescence signature can be tuned to provide a signal that either scales with protein elution or that changes rapidly near the end of useful life of the delivery system. Although payload release and particle dissolution are not driven by the same mechanism, the correlations between luminescence and payload elution for the various formulations can be used to define design rules for this self-reporting delivery system.

Delivery by Design (DbD): A Standardized Approach to the Development of Efficacious Nanoparticle- and Microparticle-Based Delivery Systems.

The design and development of nanoparticle- and microparticle-based delivery systems for the encapsulation, protection, and controlled release of active agents has grown considerably in the agrochemical, cosmetic, food, personal care, and pharmaceutical industries. These colloidal delivery systems can be utilized to overcome problems such as poor solubility, low activity, and chemical instability of active agents, as well as to create novel functional attributes such as controlled or targeted delivery. The purpose of this article is to develop a systematic approach, referred to as "delivery-by-design" (DbD), to make the design and fabrication process more efficient and effective. Initially, a brief review of some of the challenges associated with incorporating active agents into commercial products is given, and then an overview of different kinds of simple and complex colloidal delivery systems is given. The DbD approach is then presented as a series of stages: (1) definition of the molecular and physicochemical properties of the active agent; (2) definition of the required physicochemical, sensory, and functional attributes of the end-product; (3) specification of the required attributes of the colloidal delivery system; (4) specification of particle properties and delivery system selection; (5) optimization of delivery system manufacturing process; (6) establishment and implementation of delivery system testing protocol; and (7) optimization of delivery system performance. Utilization of the DbD approach may lead to more rapid design of efficacious and economically viable colloidal delivery systems for commercial applications.

Dexamethasone Controlled Release on TGF-β1 Treated Vocal Fold Fibroblasts.

Corticosteroids may be beneficial in treating vocal fold scarring. Current drug delivery methods do not permit controlled corticosteroid release. Here we investigate the effects of poly-lactic-co-glycolic acid (PLGA) microparticles loaded with the corticosteroid dexamethasone in reducing collagen synthesis and inflammation in vocal fold fibroblasts treated with and without TGF-β1. Experimental, in vitro study. PLGA microparticles of differing molecular weight and terminating moieties were synthesized using a hydrogel template method. The release of dexamethasone was characterized from these microparticles over 4 days. Based on the release studies, ester-terminated low molecular weight PLGA microparticles were loaded with dexamethasone and applied to TGF-β1 treated vocal fold fibroblasts for 4 days. Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assays (ELISAs) were used to assess the effects of released dexamethasone on collagen synthesis and inflammatory mediators. COL3A1 and COL1A2 were significantly down-regulated after exposure to ester-terminated low molecular weight PLGA microparticles loaded with dexamethasone. The loaded microparticles also reduced interleukin-6 synthesis. These data show promise in using a PLGA microparticle-based delivery system to control dexamethasone release over 4 days. Our findings lay the groundwork for developing more effective treatments for vocal fold scarring.

ROS-responsive microspheres for on demand antioxidant therapy in a model of diabetic peripheral arterial disease

A new microparticle-based delivery system was synthesized from reactive oxygen species (ROS)-responsive poly(propylene sulfide) (PPS) and tested for “on demand” antioxidant therapy. PPS is hydrophobic but undergoes a phase change to become hydrophilic upon oxidation and thus provides a useful platform for ROS-demanded drug release. This platform was tested for delivery of the promising anti-inflammatory and antioxidant therapeutic molecule curcumin, which is currently limited in use in its free form due to poor pharmacokinetic properties. PPS microspheres efficiently encapsulated curcumin through oil-in-water emulsion and provided sustained, on demand release that was modulated in vitro by hydrogen peroxide concentration. The cytocompatible, curcumin-loaded microspheres preferentially targeted and scavenged intracellular ROS in activated macrophages, reduced in vitro cell death in the presence of cytotoxic levels of ROS, and decreased tissue-level ROS in vivo in the diabetic mouse hind limb ischemia model of peripheral arterial disease. Interestingly, due to the ROS scavenging behavior of PPS, the blank microparticles also showed inherent therapeutic properties that were synergistic with the effects of curcumin in these assays. Functionally, local delivery of curcumin-PPS microspheres accelerated recovery from hind limb ischemia in diabetic mice, as demonstrated using non-invasive imaging techniques. This work demonstrates the potential for PPS microspheres as a generalizable vehicle for ROS-demanded drug release and establishes the utility of this platform for improving local curcumin bioavailability for treatment of chronic inflammatory diseases.

Microparticle-based technologies for vaccines

Microparticles have been effectively used for many years as delivery systems for drugs and therapeutic proteins. Their application to the delivery of vaccines is not as extensive, but is growing. Utility has been demonstrated for the delivery of various types of vaccines (e.g., recombinant proteins, plasmid DNA, and peptides) and other vaccine components (e.g., immune potentiators). With respect to delivery of immune potentiators, synergistic effects are often observed whereby much more potent immune responses are induced with a combination than with either component alone. Hence, the prospects for broad application of microparticle-based delivery systems for vaccines are excellent.

Cell contact dependent extended release of adenovirus by microparticles in vitro

Adenoviral vectors remain one of the most promising methods of gene delivery but are plagued by several inherent problems including immune inactivation and transient expression. This paper reports a novel microparticle-based delivery system for adenovirus that allows high uptake of virus, stable complex formation and extended release. In addition, this microparticle/adenovirus complex has been demonstrated to only release virus upon cell contact. The significant clinical implications of this delivery system are discussed.