Microsphere System Research Articles

GAPDH-Silence Microsphere via Reprogramming Macrophage Metabolism and eradicating Bacteria for Diabetic infection bone regeneration

Macrophage metabolism dysregulation, which is exacerbated by persistent stimulation in infectious and inflammatory diseases, such as diabetic infectious bone defects (DIBD), eventually leads to the failure of bone repair. Here, we have developed an injectable, macrophage-modulated GAPDH-Silence drug delivery system. This microsphere comprises chondroitin sulfate methacrylate (CM) and methacrylated gelatin (GM), while the dimethyl fumarate (DMF)-loaded liposome (D-lip) is encapsulated within the microsphere (CM@GM), named D-lip/CM@GM. Triggered by the over-expressed collagenase in DIBD, the microspheres degrade and release the encapsulated D-lip. D-lip could modulate metabolism by inhibiting GAPDH, which suppresses the over-activation of glycolysis, thus preventing the inflammatory response of macrophages in vitro. While beneficial for macrophages, D-lip/CM@GM is harmful to bacteria. GAPDH, while crucial for glycolysis of staphylococcal species (S. aureus), can be effectively countered by D-lip/CM@GM. We are utilizing existing drugs in innovative ways to target central metabolism for effective eradication of bacteria. In the DIBD model, our results confirmed that the D-lip/CM@GM enhanced bacteria clearance and reprogrammed dysregulated metabolism, thereby significantly improving bone regeneration. In conclusion, this GAPDH-Silence microsphere system may provide a viable strategy to promote diabetic infection bone regeneration.

Bioinspired micro-nano hierarchical delivery system for sequential targeted therapy of inflammatory bowel disease

Inflammatory bowel disease (IBD) constitutes an immense health and economic burden worldwide, highlighting the need for improved therapy. Up to now, various delivery systems have been proposed to enhance IBD treatment. Herein, inspired by cellular communication in nature, we present a novel micro-nano hierarchical microsphere system with the enhanced targeting capability for IBD treatment. The hierarchical microspheres are designed for oral delivery, with astaxanthin nanoparticles in the core and Zein protein shell. Similar to a stepwise process of cellular communication, microscale spheres can escape from the gastric acid due to Zein coating. Once reach into the intestine, mucoadhesive Zein coating and the core could be enzymatically digested, following the targeted release of astaxanthin nanoparticles. Particularly, these astaxanthin nanoparticles are endowed with the mitochondria targeting capability, thereby greatly attenuating pro-inflammatory response of macrophages. Based on these features, practical performances of the hierarchical delivery system have been investigated in both acute and chronic colitis model. Animal experiments have revealed the desired therapeutic effects of the hierarchical microspheres by inhibiting inflammatory responses and modulating gut microbiota. These results suggested the present hierarchical delivery system offers a stepwise strategy for nanodrug delivery to the intestine as well as the effective treatment of IBD.

Extremely lower lasing threshold in Er3+/Yb3+ co-doped phosphate dual glass microspheres

Erbium-doped glass microsphere laser systems hold significant promise in the applications of bio-medicine and optical fiber sensing. However, their development has been hindered by the relatively high laser pump threshold. In this study, we proposed a unique dual microsphere system where two microspheres are affixed to a single-mode fiber taper and achieved a remarkably low lasing threshold of 19 μW for single-mode laser emission at 1544 nm. This is in sharp contrast with the lasing threshold of 56 μW observed in single microspheres. Our findings represent a significant achievement in the development of low-threshold, compact infrared laser sources for emerging applications in photonics.

Composite Mineralized Collagen/Polycaprolactone Scaffold-Loaded Microsphere System with Dual Osteogenesis and Antibacterial Functions.

Biomaterials play an important role in treating bone defects. The functional characteristics of scaffolds, such as their structure, mechanical strength, and antibacterial and osteogenesis activities, effectively promote bone regeneration. In this study, mineralized collagen and polycaprolactone were used to prepare loaded porous scaffolds with bilayer-structured microspheres with dual antibacterial and osteogenesis functions. The different drug release mechanisms of PLGA and chitosan in PLGA/CS microspheres caused differences in the drug release models in terms of the duration and rate of Pac-525 and BMP-2 release. The prepared PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffolds were analyzed in terms of physical characteristics, bioactivity, and antibacterial properties. The scaffolds with a dimensional porous structure showed similar porosity and pore diameter to cancellous bone. The release curve of the microspheres and scaffolds with high encapsulation rates displayed the two-stage release of Pac-525 and BMP-2 over 30 days. It was found that the scaffolds could inhibit S. aureus and E. coli and then promote ALP activity. The PLGA(BMP-2)/CS(Pac-525)@MC/PCL scaffold could be used as a dual delivery system to promote bone regeneration.

Preparation and Characterization of Responsive Cellulose-Based Gel Microspheres for Enhanced Oil Recovery.

As an important means to enhance oil recovery, ternary composite flooding (ASP flooding for short) technology has achieved remarkable results in Daqing Oilfield. Alkalis, surfactants and polymers are mixed in specific proportions and injected into the reservoir to give full play to the synergistic effect of each component, which can effectively enhance the fluidity of crude oil and greatly improve the oil recovery. At present, the technology for further improving oil recovery after ternary composite flooding is not mature and belongs to the stage of technical exploration. The presence of alkaline substances significantly alters the reservoir's physical properties and causes considerable corrosion to the equipment used in its development. This is detrimental to both the environment and production. Therefore, it is necessary to develop green displacement control agents. In the reservoir environment post-ASP flooding, 2-(methylamino)ethyl methacrylate and glycidyl methacrylate were chosen as monomers to synthesize a polymer responsive to alkali, and then grafted with cellulose nanocrystals to form microspheres of alkali-resistant swelling hydrogel. Cellulose nanocrystals (CNCs) modified with functional groups and other materials were utilized to fabricate hydrogel microspheres. The product's structure was characterized and validated using Fourier transform infrared spectroscopy and X-ray diffraction. The infrared spectrum revealed characteristic absorption peaks of CNCs at 1165 cm-1, 1577 cm-1, 1746 cm-1, and 3342 cm-1. The diffraction spectrum corroborated the findings of the infrared analysis, indicating that the functional modification occurred on the CNC surface. After evaluating the swelling and erosion resistance of the hydrogel microspheres under various alkaline conditions, the optimal particle size for compatibility with the target reservoir was determined to be 6 μm. The potential of cellulose-based gel microspheres to enhance oil recovery was assessed through the evaluation of Zeta potential and laboratory physical simulations of oil displacement. The study revealed that the absolute value of the Zeta potential for gel microspheres exceeds 30 in an alkaline environment with pH values ranging from 7 to 14, exhibiting a phenomenon where stronger alkalinity correlates with a greater absolute value of Zeta potential. The dispersion stability spans from good to excellent. The laboratory oil displacement simulation experiment was conducted using a cellulose-based gel microsphere system following weak alkali ASP flooding within the pH value range from 7 to 10. The experimental interventions yielded recovery rates of 2.98%, 3.20%, 3.31%, and 3.38%, respectively. The study indicates that cellulose-based gel microspheres exhibit good adaptability in alkaline reservoirs. This research offers a theoretical foundation and experimental approaches to enhance oil recovery techniques post-ASP flooding.

Influence of Carbonyl Iron Particles (CIP) and Glass Microspheres on Thermal Properties of Poly(lactic acid) (PLA).

In this investigation, composite poly(lactic acid) (PLA) systems of hollow glass microspheres (MS) and carbonyl iron particles (CIP) were processed and characterized to investigate the effects of using conductive and insulating particles as additives in a polymer system. PLA-MS and PLA-CIP were set at the two levels of 3.94 and 7.77 vol.% for each particle type to study the effects of the particle material type and loading on neat PLA's thermal properties. It was observed during the twin-screw extrusion that the addition of CIP greatly decreased the viscosity of the PLA melt during processing. Correlations determined using thermogravimetric analysis, differential scanning calorimetry, thermal conductivity, and shear rheology provided insights into how thermal stability was affected. The incorporation of MS and CIP altered thermal properties such as the glass transition temperature (Tg), melting temperature (Tm), and cold crystallization temperature (Tcc). The metal CIP-filled systems had large increases in their thermal conductivity values and viscoelastic transitions compared to those with PLA that were correlated with the observed overheating during extrusion.

Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration

Despite numerous studies on chondrogenesis, the repair of cartilage—particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited. In this study, we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals, enabling sequential immunomodulation and endogenous articular cartilage regeneration. We first integrated the chondrogenic growth factor transforming growth factor-β3 (TGF-β3) into mesoporous silica nanoparticles (MSNs). Then, TGF-β3@MSNs and insulin-like growth factor 1 (IGF-1) were encapsulated within microspheres made of polydopamine (pDA). In the final step, growth factor-loaded MSN@pDA and a chitosan (CS) hydrogel containing platelet-derived growth factor-BB (PDGF-BB) were blended to produce growth factors loaded composite microspheres (GFs@μS) using microfluidic technology. The presence of pDA reduced the initial acute inflammatory response, and the early, robust release of PDGF-BB aided in attracting endogenous stem cells. Over the subsequent weeks, the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation. μS were incorporated into an acellular cartilage extracellular matrix (ACECM) and combined with a polydopamine-modified polycaprolactone (PCL) structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix, resulting in enhanced cartilage repair and patellar cartilage protection. This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling, leading to efficient articular cartilage regeneration.

Dental pulp stem cells-loaded kartogenin-modified hydrogel microspheres with chondrocyte differentiation property for cartilage repair

Stem cell-based regimens have evolved as a promising approach to cartilage reparations. Research efforts in this realm aim to enhance the therapeutic capabilities of stem cells and develop more effective cell delivery strategies. Herein, we present novel dental pulp stem cells (DPSCs)-loaded kartogenin-modified hydrogel microspheres with chondrocyte differentiation property for temporomandibular joint (TMJ) osteoarthritis treatment. Leveraging microfluidic technology, DPSCs were successfully encapsulated in hydrogel microspheres, serving as the pivotal contributors to cartilage repair. By modifying the hydrogel with kartogenin, these microspheres facilitated sustained stimulation of DPSCs’ chondrogenic differentiation. In vitro experimental results revealed that the DPSCs exhibited advanced cartilage-forming differentiation, as evidenced by the up-regulation of relative gene expressions and protein markers. Additionally, the DPSCs-loaded microspheres system displayed a capacity to regenerate and repair tissue at the cartilage defects in a TMJ osteoarthritis animal model. Thus, the DPSCs-loaded kartogenin-modified hydrogel microspheres exhibit significant promise for cartilage repair, showcasing the substantial potential for future clinical applications.

Preparation of μ-HMX/C-Based Composite Energy Composite Microspheres by Microdroplet Technology.

Taking μ-HMX particles as the main research subject, a set of microdroplet sphericalization coating technology platforms was designed and constructed to realize the preparation of composite microspheres by sphericalization coating of μ-HMX. The suspension stability of μ-HMX particles and the mechanism of droplet formation were investigated, and the application effect of nanocarbon materials was also analyzed. The results showed that the prepared sample microspheres all showed a better spherical morphology, as well as good dispersibility; the samples with micron-sized particles for spherical coating had a lower thermal decomposition temperature, a higher energy release efficiency, lower mechanical sensibility, and better combustion performance; the incorporation of CNFs changed the combustion mode of the system, which resulted in the microsphere system of μ-HMX having a good safety performance. The stability and feasibility of uniform spheronization when the dispersed phase is a low-concentration particle suspension system in the spheronization encapsulation process by microdroplet technology were verified.

Alginate/silk fibroin/Zn2+ composite microspheres for site-specific delivery for enhanced ulcerative colitis therapy

The limited therapeutic efficacy of oral medications against ulcerative colitis (UC) is attributed to inadequate drug exposure to inflammation site in the colon. To address this challenge, we developed a pH-triggered oral hydrogel microsphere system composed of alginate/silk fibroin (Alg/SF) using zinc ions (Zn2+) as a crosslink agent for colon-targeted delivery. This system, with moderate gelation toughness, can protect the anti-inflammatory drug bornyl acetate (BA) from gastric degradation, ensuring its delivery to the colon. SF effectively shields the microspheres during passage through the small intestine and then facilitates rapid drug release upon reaching the colon. We evaluated the efficacy of this strategy in murine models of both acute and chronic colitis, demonstrating its significant capacity to attenuate pro-inflammatory cytokine secretion, enhance intestinal barrier restitution, and modulate immune cell responses for effective amelioration of colitis-associated symptoms. Upon oral administration of microspheres, their therapeutic efficacy against both acute and chronic UC is demonstrated to be superior to that of a widely used clinical drug, 5-aminosalicylic acid. Overall, the oral hydrogel microspheres offer a promising approach to enhance the therapeutic outcomes of small molecule drug against UC.

Formulation, physicochemical characterisation, and in vitro evaluation of quercetin-alginate microsphere system

Formulation, physicochemical characterisation, and in vitro evaluation of quercetin-alginate microsphere system

MMP13-responsive hydrogel microspheres for osteoarthritis treatment by precise delivery of celecoxib

Osteoarthritis (OA) is characterized by cartilage degradation, inflammatory responses, and osteophyte formation. Matrix metalloproteinase 13 (MMP13) is a hallmark of OA development, and increased MMP13 expression is closely associated with extracellular matrix degradation. MMP13 expression varies significantly at different stages of OA progression. While cyclooxygenase 2 (COX-2) inhibitors are commonly used to treat OA, their long-term systemic administration increases the risks of adverse effects. Therefore, with the aim of achieving localized and responsive delivery of the COX-2 inhibitor celecoxib, the current study investigated an innovative MMP13-responsive micro-nano hydrogel microsphere system. Celecoxib-loaded cationic liposomes are non-covalently attached within the microsphere, enabling controlled drug release for OA treatment. In an OA environment with elevated MMP13 expression, the system is degraded via the action of MMP13 substrate peptide (MMP13sp), facilitating accelerated release of drug-loaded liposomes to improve the inflammatory microenvironment and treat OA rapidly. Compared to a phosphate-buffered saline solution with hyaluronidase (HAase), the prepared hyaluronic acid methacrylate microspheres HAMA/MMP13sp/Lipo@celecoxib exhibited rapid degradation in a solution containing a physiological concentration of MMP13/HAase, demonstrating specific enzyme responsiveness for precise anti-inflammatory drug release. The MMP13-responsive hydrogel microsphere system achieves intelligent and controllable drug release in OA, effectively decelerating disease progression and promoting articular cartilage repair.

Tacrolimus Monitoring in Liver Transplant Recipients, Posttransplant Cholestasis: A Comparative Between 2 Commercial Immunoassays and a Liquid Chromatography-Tandem Mass Spectrometry Method.

Cholestasis commonly occurs after orthotopic liver transplantation. It can be extrahepatic because of mechanical obstruction or intrahepatic because of various causes. During cholestasis episodes, blood concentrations of tacrolimus (TAC) metabolites may increase, potentially affecting TAC concentrations measured by immunoassays. This study aimed to simultaneously evaluate the analytical performance of 2 TAC immunoassays, a quantitative microsphere system (QMS) immunoassay, and chemiluminescence microparticle immunoassay, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) as a reference method in liver transplant recipients. This single-center study included 265 patients who underwent orthotopic liver transplantation. In total, 942 blood samples were collected. TAC trough concentrations were measured using LC-MS/MS and 2 immunoassays in parallel. The plasma concentrations of conjugated bilirubin were measured in all samples. The results were analyzed using Bland-Altman plots and Passing-Bablok regressions. The Bland-Altman plot analysis showed that the TAC QMS immunoassay has a significant bias (+37%) compared with LC-MS/MS, and this bias was higher in patients with cholestasis with hyperbilirubinemia (≤+70% in patients with conjugated bilirubin >150 µmol/L). In comparison, the chemiluminescence microparticle immunoassay showed acceptable analytical performance in patients with hyperbilirubinemia (bias <10%). In agreement with previous findings, the TAC QMS immunoassay showed a positive bias compared with LC-MS/MS. This bias is remarkably high in patients with cholestasis and hyperbilirubinemia, suggesting the cross-reactivity of TAC metabolites with the monoclonal antibody used in the QMS immunoassay.

Immune-defensive microspheres promote regeneration of the nucleus pulposus by targeted entrapment of the inflammatory cascade during intervertebral disc degeneration

Sustained and intense inflammation is the pathological basis for intervertebral disc degeneration (IVDD). Effective antagonism or reduction of local inflammatory factors may help regulate the IVDD microenvironment and reshape the extracellular matrix of the disc. This study reports an immunomodulatory hydrogel microsphere system combining cell membrane-coated mimic technology and surface chemical modification methods by grafting neutrophil membrane-coated polylactic-glycolic acid copolymer nanoparticles loaded with transforming growth factor-beta 1 (TGF-β1) (T-NNPs) onto the surface of methacrylic acid gelatin anhydride microspheres (GM) via amide bonds. The nanoparticle-microsphere complex (GM@T-NNPs) sustained the long-term release of T-NNPs with excellent cell-like functions, effectively bound to pro-inflammatory cytokines, and improved the release kinetics of TGF-β1, maintaining a 36 day-acting release. GM@T-NNPs significantly inhibited lipopolysaccharide-induced inflammation in nucleus pulposus cells in vitro, downregulated the expression of inflammatory factors and matrix metalloproteinase, and upregulated the expression of collagen-II and aggrecan. GM@T-NNPs effectively restored intervertebral disc height and significantly improved the structure and biomechanical function of the nucleus pulposus in a rat IVDD model. The integration of biomimetic technology and nano-drug delivery systems expands the application of biomimetic cell membrane-coated materials and provides a new treatment strategy for IVDD.

Dispersion and Spatial Distribution of Air Voids or Microspheres in Assessing Frost Resistance of Concrete

Abstract The standard spacing factor developed by Powers is typically used to evaluate the quality of the air void system in hardened concrete, but it does not always correlate with durability of the concrete. Several air void spacing equations, which are also applicable when polymeric microspheres are used in place of air entrainment, have been proposed because of the need for a more robust and comprehensive basis to evaluate the quality of the air void system. However, the spacing parameters provided by the various proposed equations, when used as sole measures in predicting the frost resistance of concrete, do not seem to do any better than the standard spacing factor. Dispersion and spatial distribution have been shown to be effective ways of describing air void or microsphere systems in hardened concrete because they have been quantified to establish criteria to assess the frost resistance of concrete. In this paper, dispersion and distribution factors are further elaborated upon to explain how they characterize zones that are protected by air voids or microspheres in the concrete. Criteria to assess the durability of concrete under rapid cycles of freezing and thawing based on the dispersion and distribution factors are linked to the exposure classes defined in the ACI 318 Code and in the recently proposed Unified Durability Guidance in ACI Committee Documents.

PLGA micro/nanoparticle vaccination elicits non-tumor antigen specific resident memory CD8+ T cell protection from hepatocellular carcinoma.

Together, tumor and virus-specific tissue-resident CD8+ memory T cells (TRMs) of hepatocellular carcinoma (HCC) patients with Hepatitis B virus (HBV) infection can provide rapid frontline immune surveillance. The quantity and activity of CD8+ TRMs were correlated with the relapse-free survival of patients with improved health. However, HBV-specific CD8+ TRMs have a more exhausted phenotype and respond more actively under anti-PDL1 or PD1 treatment of HBV+HCC patients. Vaccination strategies that induce a strong and sustained CD8+ TRMs response are quite promising. Herein, a biodegradable poly(D,L-lactide-co-glycolide) microsphere and nanosphere particle (PLGA N.M.P) delivery system co-assembled by anti-PD1 antibodies (aPD1) and loaded with ovalbumin (OVA-aPD1 N.M.P) was fabricated and characterized for size (200 nm and 1 μm diameter), charge (-15 mV), and loading efficiencies of OVA (238 μg mg-1 particles) and aPD1 (40 μg mg-1 particles). OVA-aPD1 N.M.P could stimulate the maturation of BMDCs and enhance the antigen uptake and presentation by 2-fold compared to free OVA. The nanoparticles also induced the activation of macrophages (RAW 264.7) to produce a high level of cytokines, including TNF-α, IL-6 and IL-10. In vivo stimulation of mice using OVA-aPD1 N.M.P robustly enhanced IFN-γ-producing-CD8+ T cell infiltration in tumor tissues and the secretion of IgG and IgG2a/IgG1 antibodies. OVA-aPD1 N.M.P delivered OVA to increase the activation and proliferation of OVA-specific CD8+ TRMs, and its combination with anti-PD1 antibodies promoted complete tumor rejection by the reversal of tumor-infiltrating CD8+ T cell exhaustion. Thus, PLGA N.M.P could induce a strong CD8+ TRMs response, further highlighting its therapeutic potential in enhancing an antitumor immune response.

Hypoxia and Matrix Metalloproteinase 13-Responsive Hydrogel Microspheres Alleviate Osteoarthritis Progression In Vivo.

The occurrence of osteoarthritis (OA) is highly associated with the inflammatory hypoxic microenvironment. Yet currently no attention has been paid to fabricating hypoxia-responsive platforms for OA treatment. Herein, an injectable hydrogel microsphere system (HAM-SA@HCQ) focusing on the hypoxic inflamed joint is prepared with methacrylate-modified sulfonated azocalix[4]arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and dithiol-terminated matrix metalloproteinase 13 (MMP-13) sensitive peptide via a microfluidic device and photo crosslinking technique, followed by encapsulation of the anti-inflammatory drug hydroxychloroquine (HCQ) through host-guest interaction. Owing to the hydrophobic deep cavity, phenolic units, and azo bonds of SAC4A-MA, the hydrogel microspheres show strong drug loading capacity, prominent reactive oxygen species (ROS) scavenging capability, and specific hypoxia-responsive drug release ability. In the OA tissue microenvironment, the hydrogel microspheres undergo degradation by excessive MMP-13 and release HCQ under the hypoxia condition, which synergizes with the ROS-scavenging calixarene to inhibit the inflammatory response of macrophages. After being injected into the OA-inflamed joint, the HAM-SA@HCQ can significantly attenuate the oxidative stress, downregulate the expression of hypoxia-induced factor-1α and inflammatory cytokines, and prevent the cartilage from being destroyed.

Transplantation of active nucleus pulposus cells with a keep-charging hydrogel microsphere system to rescue intervertebral disc degeneration

BackgroundCell transplantation has been demonstrated as a promising approach in tissue regeneration. However, the reactive oxygen species (ROS) accumulation and inflammation condition establish a harsh microenvironment in degenerated tissue, which makes the transplanted cells difficult to survive.MethodsIn this study, we constructed a keep-charging hydrogel microsphere system to enable cells actively proliferate and function in the degenerated intervertebral disc. Specifically, we combined Mg2+ to histidine-functionalized hyaluronic acid (HA-His-Mg2+) through coordination reaction, which was further intercrossed with GelMA to construct a double-network hydrogel microsphere (GelMA/HA-His-Mg2+, GHHM) with microfluidic methods. In vitro, the GHHM loaded with nucleus pulposus cells (GHHM@NPCs) was further tested for its ability to promote NPCs proliferation and anti-inflammatory properties. In vivo, the ability of GHHM@NPCs to promote regeneration of NP tissue and rescue intervertebral disc degeneration (IVDD) was evaluated by the rat intervertebral disc acupuncture model.ResultsThe GHHM significantly enhanced NPCs adhesion and proliferation, providing an ideal platform for the NPCs to grow on. The loaded NPCs were kept active in the degenerative intervertebral disc microenvironment as charged by the Mg2+ in GHHM microspheres to effectively support the loaded NPCs to reply against the ROS-induced inflammation and senescence. Moreover, we observed that GHHM@NPCs effectively alleviated nucleus pulposus degeneration and promoted its regeneration in the rat IVDD model.ConclusionIn conclusion, we constructed a keep charging system with a double-network hydrogel microsphere as a framework and Mg2+ as a cell activity enhancer, which effectively maintains NPCs active to fight against the harsh microenvironment in the degenerative intervertebral disc. The GHHM@NPCs system provides a promising approach for IVDD management.Graphical

Development of a new inhaled swellable microsphere system for the dual delivery of naringenin-loaded solid lipid nanoparticles and doxofylline for the treatment of asthma

This study developed a new dual delivery system of naringenin (NRG), a polyphenol, and doxofylline (DOX), a xanthine derivative, as an inhaled microsphere system. In this system, NRG has been first loaded into glyceryl tristearate-based solid lipid nanoparticles (NRG SLN), which were further loaded with DOX into swellable chitosan-tripolyphosphate-based microspheres (NRG SLN DOX sMS). The system was characterised based on particle size, PDI, zeta potential, surface morphology (SEM, AFM, and TEM), solid-state and chemical properties (XRD, IR, and NMR), aerodynamic parameters, drug loading, entrapment efficiency and in vitro drug release study. The optimised NRG SLN DOX sMS exhibited particle size, zeta potential, and PDI of 2.1 µm, 31.2 mV, and 0.310, respectively; a drug entrapment efficiency > 79%; a drug loading efficiency > 13%; cumulative drug releases of about 78% for DOX and 72% for NRG after 6 and 12 hours, respectively; good swelling and desirable aerodynamic properties. In addition, in vivo studies conducted in mice, a murine model of asthma showed significant reductions in serum bicarbonate and eosinophil counts and improvement in respiratory flow rate, tidal volume, and bronchial wall lining compared with the asthmatic control group. Overall, this novel inhalable dual-delivery system may represent a good alternative for the effective treatment of asthma.

AN UP-TO-DATE REVIEW: MICROSPHERES AS A NEW DRUG DELIVERY SYSTEM

The application of microsphere systems in drug preparations has seen a significant increase in recent years for various purposes. Microsphere systems can be utilized in a range of drug preparations, utilizing polymer types that are appropriate for the intended release target. Microspheres offer numerous benefits and can be used in various applications, including spacer applications, medication administration, and medical diagnostics. Microspheres have minimal negative effects, a more extended therapeutic effect, require fewer doses, and provide more consistent medication absorption. Additionally, they are adaptable, offer effective encapsulation, and are cost-effective. This overview was compiled to provide an up-to-date summary of the latest developments in new drug delivery systems utilizing microsphere dosage forms. Literature from Scopus, ScienceDirect, and PubMed from 2019 to 2022 was searched to provide the latest information. The use of microsphere systems is categorized into various new drug delivery routes, including gastroretentive, colon, nasal and pulmonary, parenteral, ocular, and topical applications.