Sustained-release Microspheres Research Articles

Development of 1 Month Sustained-Release Microspheres Containing Liraglutide for Type 2 Diabetes Treatment.

Liraglutide has been extensively applied in the treatment of type 2 diabetes mellitus (T2DM), but its 11-15 h half-life resulted in daily administration, which led to poor patient compliance. This study aimed to solve this problem by developing liraglutide-loaded microspheres with a 1 month sustained release prepared by the W1/O/W2 method combined with the premix membrane emulsification technique to improve therapeutic efficacy. Remarkably, we found that the amphiphilic properties of liraglutide successfully reduced the oil-water interfacial tension, resulting in a stable primary emulsion and decreasing the level of drug leakage into the external water phase. As a result, exceptional drug loading (>8%) and encapsulation efficiency (>85%) of microspheres were achieved. Furthermore, the uniformity in microsphere size facilitated an in-depth exploration of the structural characteristics of liraglutide-loaded microspheres. The results indicated that the dimensions of the internal cavities of the microspheres were significantly influenced by the size of the inner water droplets in the primary emulsion. A denser and more uniform cavity structure decreased the initial burst release, improving the release process of liraglutide from the microspheres. To evaluate the release behavior of liraglutide from microspheres, a set of in vitro release assays and in vivo pharmacodynamics were performed. The liraglutide-loaded microspheres effectively decreased fasting blood glucose (FBG) levels and hemoglobin A1c (HbA1c) levels while enhancing the pancreatic and hepatic functions in db/db mice. In conclusion, liraglutide sustained-release microspheres showed the potential for future clinical applications in the management of T2DM and provided an effective therapeutic approach to overcoming patient compliance issues.

Fabrication and Characterization of Sustained-Release Eudragit RSPO Microsphere of Lornoxicam by Spray Drying Technique

Background: Lornoxicam is a potent non-steroidal anti-inflammatory drug (NSAID) with strong analgesic properties; however, its short half-life necessitates frequent administration for sustained efficacy. Objective: The objective of the present study was to identify critical formulation parameters affecting sustained release Eudragit RSPO microsphere of lornoxicam employing the concept of design of experiments Method: The lornoxicam-loaded microspheres were prepared using a spray drying technique by optimizing the drug:polymer ratio(X1) and inlet air temperature (X2) using a 32 full factorial design. The percentage drug entrapment (Y1), percentage yield (Y2) and cumulative percentage of the drug dissolved at 18 hr (Y3) were selected as dependent variables. Microspheres were evaluated for percentage drug entrapment, mean particle size, percentage yield, in vitro drug release study and scanning electron microscopy (SEM). Result: The optimized batch showed 84.51% drug release after 18 h with significantly higher drug entrapment and percentage yield. The optimization was further verified using overlay and desirability plots. The sustained release behavior of the drug from microspheres in GIT was displayed. The predicted and observed responses for the optimized formulation were in close agreement with the release profile of the drug. Conclusion: The sustained release microspheres of lornoxicam may prove to be an effective analgesic with excellent anti-inflammatory potential.

Up-to-date Combinational Polymeric Approaches for the Enhancement of Drug Absorption and Membrane Transductivity

Abstract: Many of the challenges concerning pharmaceutical compounds are involved in the tuning of their physical properties and controlled and targeted drug delivery, in order to acquire the optimum therapeutic effect. With these challenges in mind and with the recent emergence of advanced materials, various combinational polymeric approaches have been applied. The use of coordination polymers, which are hybrid inorganic-organic materials, consists of transition metals and multidentate organic ligands and have been proven to prolong the release and increase the drug permeation rate of active pharmaceutical ingredients (APIs). Another recent approach is the preparation of deformable polymeric nanoparticles (DPN) that require the physical incorporation of a lipid in a polymeric micelle, offering flexible and deformable phase properties. It has been shown that skin delivery efficiency could be increased due to this deformable phase. Enhanced skin permeation was also observed when TAT peptides were chemically attached to the DPNs. Other recent approaches, such as microarray patches, sustained release microspheres, nanoparticles coated with biological membranes, nanosponges, and lipid-based nanoparticles, modified by polymers, have also been able to improve the pharmacokinetic profiles of APIs and are also discussed in this paper.

IGF-PLGA microspheres promote angiogenesis and accelerate skin flap repair and healing by inhibiting oxidative stress and regulating the Ang 1/Tie 2 signaling pathway

Random flaps are widely used in the treatment of injuries, tumors, congenital malformations, and other diseases. However, postoperative skin flaps are prone to ischemic necrosis, leading to surgical failure. Insulin-like growth factor- 1(IGF-1) belongs to the IGF family and exerts its growth-promoting effects in various tissues through autocrine or paracrine mechanisms. Its application in skin flaps and other traumatic diseases is relatively limited. Poly (lactic-co-glycolic acid) (PLGA) is a degradable high-molecular-weight organic compound commonly used in biomaterials. This study prepared IGF-PLGA sustained-release microspheres to explore their impact on the survival rate of flaps both in vitro and in vivo, as well as the mechanisms involved. The research results demonstrate that IGF-PLGA has a good sustained-release effect. At the cellular level, it can promote 3T3 cell proliferation by inhibiting oxidative stress, inhibit apoptosis, and enhance the tube formation ability of human umbilical vein endothelial cells (HUVEC) . At the animal level, it accelerates flap healing by promoting vascularization through the inhibition of oxidative stress. Furthermore, this study reveals the role of IGF-PLGA in activating the Angiopoietin-1(Ang1)/Tie2 signaling pathway in promoting flap vascularization, providing a strong theoretical basis and therapeutic target for the application of IGF-1 in flaps and other traumatic diseases.

Mn-doped geopolymers photocatalysts with sustained-release OH− for highly efficient degradation of malachite green and tetracycline

Hydroxyl radicals (•OH) are the primary reactive groups in photocatalytic reactions. However, the stability and long-term effectiveness of photocatalysis in degrading dye wastewater and antibiotic contaminants remains a major challenge. In this study, the sustained-release microspheres containing OH− were prepared by Mn-doped metakaolin-based geopolymers (Mn-MGPs), and a strategy combining defect engineering and OH− sustained-release was presented. A large number of oxygen vacancies (O), which can enhance the light absorption properties, can generate superoxide radicals (O2•-) on the catalyst surface and promote the formation of (•OH) to fabricate efficient heterojunction photocatalysts. The photocatalysts were systematically characterized for photocatalytic activity and long-term effectiveness in the degradation of malachite green (MG) and tetracycline (TC). The mechanism of the enhanced photocatalytic performance of the catalysts was investigated by characterization and DFT theoretical calculations, and the pollutant degradation pathway was proposed. This study provides an innovative approach to the controlled design of valence heterostructures.

Development and optimization of sustained release triptolide microspheres.

Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium wilfordii Hook.f., is considered to have promising potential for clinical use in treating rheumatoid arthritis. However, its clinical application has been limited by the narrow therapeutic window, side effects associated with plasma drug fluctuations, low oral bioavailability, and poor patient compliance with the long and frequent dosing regimen. An extended drug release preparation may address these limitations. The aim of this work was therefore to develop, formulate and optimize sustained release triptolide microspheres with poly (lactide-co-glycolide) (PLGA). Triptolide-loaded microspheres were prepared using PLGA as the matrix polymer, dichloromethane as the oil phase, and polyvinyl alcohol (PVA) as the matrix forming emulsifier. An oil-in-water (O/W) emulsion solvent evaporation technique was utilized to prepare the microspheres. Surface response methodology (RSM) coupled with central composite design (CCD) was used to optimize the formulation and a total of twenty formulations were prepared. PVA concentration (X1), PLGA concentration (X2), and theoretical drug content (X3) were selected as independent variables; and drug content (Y1), encapsulation efficiency (Y2), mean diameter (Y3) and the initial release during the first day (Y4) were taken as the response variables. The optimized formulation showed mean diameter of 42.36 μm, drug content of 7.96%, encapsulation efficiency of 80.16% and an initial release of 14.48%. The prepared microspheres exhibited a sustained release profile of triptolide in vitro over 4 weeks, which was wellfitted with a Korsmeyer-Peppas equation. However, the initial drug release (~14%) of triptolide-loaded microspheres was very high and should be specifically investigated in future studies. The results indicate that long-term sustained release microspheres of triptolide can be considered a strategy to overcome the low bioavailability and poor patient compliance with conventional triptolide tablets. The issue of initial burst release and in vivo evaluations should be specifically investigated in the future.

Formulation and Evaluation of Sustained Release Microspheres of Fexofenadine Hydrochloride by Ionotropic Gelation Method

Formulation and Evaluation of Sustained Release Microspheres of Fexofenadine Hydrochloride by Ionotropic Gelation Method

Zn2+ incorporated composite polysaccharide microspheres for sustained growth factor release and wound healing.

The development of new wound dressings has always been an issue of great clinical importance and research promise. In this study, we designed a novel double cross-linked polysaccharide hydrogel microspheres based on alginate (ALG) and hyaluronic acid methacrylate (HAMA) from gas-assisted microfluidics for wound healing. The microspheres from gas-assisted microfluidics showed an uniform size and good microsphere morphology. Moreover, this composite polysaccharide hydrogel microspheres were constructed by harnessing the fact that zinc ions (Zn2+) can cross-link with ALG as well as histidine-tagged vascular endothelial growth (His-VEGF) to achieve long-term His-VEGF release, thus promoting angiogenesis and wound healing. Meanwhile, Zn2+, as an important trace element, can exert antibacterial and anti-inflammatory effects, reshaping the trauma microenvironment. In addition, photo cross-linked HAMA was introduced into the microspheres to further improve its mechanical properties and drug release ability. In summary, this novel Zn2+ composite polysaccharide hydrogel microspheres loaded with His-VEGF based on a dual cross-linked strategy exhibited synergistic antimicrobial and angiogenic effects in promoting wound healing.

Formulation and Evaluation of Gastroretentive Floating Microspheres of TRAMADOL HCl

This study presents the formulation and evaluation of sustained-release microspheres containing Tramadol HCl. The aim was to achieve prolonged drug release for enhanced therapeutic efficacy and improved patient compliance. The microspheres were prepared using a solvent evaporation method with various combinations of polymers Agar and Pectin. The physical appearance, particle size, drug content, and moisture content were assessed for stability over time. Among the formulations, Batch F7 emerged as a standout candidate, displaying excellent buoyancy and sustained drug release characteristics. Comprehensive evaluations included in vitro drug release studies, kinetic data analysis, and stability assessments over 90 days. The study concludes that the combination of Agar and Pectin polymers in Batch F7 holds significant promise for achieving controlled drug release, suggesting its potential for advanced drug delivery systems.
 Keywords: Gastroretentive Floating Microspheres, Tramadol HCl, prolonged drug release, patient compliance

Formulation and Evaluation of Microspheres for Colon Targeted Drug Delivery Using Anthelminthics Drugs

The objective of this study was to develop sustained release microspheres for colon-targeted drug delivery system to enhance therapeutic efficacy while minimizing systemic side effects. The controlled and prolonged release of drugs in the colon can significantly improve the treatment outcomes for various colon-related diseases. Microspheres, small spherical particles with sizes ranging from 1 to 1000 micrometers, were formulated using biodegradable polymers and natural materials to ensure biocompatibility and controlled drug release. The formulation process involved the selection of appropriate polymers, such as poly lactic acid and polyglycolic acid, and the incorporation of the drug within the microspheres. Various techniques, including solvent evaporation, coacervation, and spray drying, were employed to prepare the microspheres with the desired drug-loading efficiency and particle size distribution.The formulated microspheres were extensively evaluated to assess their suitability for sustained release colon-targeted drug delivery. Evaluation parameters included drug encapsulation efficiency, particle size distribution, surface morphology and in vitro.In vitro drug release studies were conducted using simulated gastrointestinal fluids to mimic the conditions in the gastrointestinal tract. The sustained release microspheres exhibited controlled drug release over an extended period, specifically in the colon region. This sustained release profile was achieved by optimizing the polymer composition and formulation parameters, which allowed for the gradual degradation of the microspheres and subsequent release of the drug.

Optimization of O/W Emulsion Solvent Evaporation Method for Itraconazole Sustained Release Microspheres.

Itraconazole, a commonly used antifungal drug in the clinic approved by U.S. Food and Drug Administration (FDA), has been gradually found to have anti-tumor, angiogenesis inhibition and other pharmacological activities. However, its poor water solubility and potential toxicity limited its clinical application. In order to improve the water solubility and reduce the side effects caused by the high concentration of itraconazole, a novel preparation method of itraconazole sustained release microspheres was established in this study. Firstly, five kinds of polylactic acid-glycolic acid (PLGA) microspheres loaded with itraconazole were prepared by oil/water (O/W) emulsion solvent evaporation and then characterized by infrared spectroscopy. Then the particle size and morphology of the microspheres were observed by scanning electron microscope (SEM) and transmission electron microscope (TEM). After that, the particle size distribution, drug loading rate, entrapment efficiency, and drug release experiments were evaluated. Our results showed the microspheres prepared in this study had uniform particle size distribution and good integrity. Further study found that the average drug loading of the five kinds of microspheres prepared with PLGA 7505, PLGA 7510, PLGA 7520, PLGA 5020 and PLGA 0020 were 16.88, 17.72, 16.72, 16.57, and 16.64%, respectively, and the encapsulation rate all reached about 100%. More surprisingly, the release experimental results showed that the microspheres prepared with PLGA 7520 did not show sudden release, showing good sustained release performance and high drug release rate. To sum up, this study optimized the preparation method of sustained-release microspheres without sudden release, which provides a new solution for the delivery of itraconazole in the clinic.

Preparation of β-CD-Vitexin Microspheres and their Effects on SW480 Cell Proliferation.

In order to overcome the insolution and low bioavailability of the vitexin in vivo, β-cyclodextrin-vitexin (β-CD-vitexin) microspheres were prepared, and their effects on the proliferation of SW480 cells were observed. Scanning electron microscopy, ultraviolet spectrum, Fourier transform infrared spectroscopy, and release rate analysis identified the formation of β-CD-vitexin microspheres. MTT assay detected the effect of β-CD-vitexin microspheres on tumor cell proliferation at 6, 12, 24, and 48 h. Fluorescence microscopy and flow cytometry were used to observe the effect of β-CD-vitexin microspheres on the apoptosis of SW480 cells. The mRNA expression of the p53 gene was measured by qPCR. β-CD-vitexin microspheres were successfully prepared. SW480 cell proliferation was inhibited by 0.1, 0.2, and 0.4 mg/mL of β-CD-vitexin microspheres in a dose- and time-dependent manner, and the mechanism of proliferation inhibition was related to cell apoptosis caused by the upregulated expression of p53 gene. The preparation of β-CD-vitexin sustained release microspheres is feasible, and β-CDvitexin microspheres have potential anti-colorectal cancer value.

Microencapsulated bufalin: From membrane preparation to microspheres tailoring, and sustained release

Microspheres are commonly implemented in drug delivery system to enhance drug bioactivity and reduce the toxicity. Membrane emulsification is a promising technique to be applied in the preparation of microspheres for sustained release due to its easy control of the particle size. Membranes with different properties on dual sides have shown superior properties in the application of membrane emulsification. In this work, membranes with open channels and sharp pore size distribution were prepared by the novel combined solvent crystallization and polymer diffusion (CCD) technique. For the first time, the feasibility of CCD membranes with dual properties were verified for the application of membrane emulsification. Bufalin-poly(lactic-co-glycolic acid) (PLGA) microspheres were successfully prepared and the size distribution could be tuned via adopting CCD membranes with different pore sizes. The effects of membrane wettability and pore size on microspheres production were investigated for the membranes prepared by four different cooling conditions. The morphologies of microspheres were obtained by scanning electron microscope and the size distribution was analyzed by ImageJ. The in vitro release of bufalin-PLGA microspheres in various sizes exhibited distinctively, indicating the capability of controlling the release rate of the drug system via changing membrane with different properties. In this study, the most uniformly distributed bufalin-PLGA microspheres with an average size of 0.47 µm were achieved through membrane emulsification using the optimal CCD membranes. The as-prepared bufalin-PLGA microspheres exhibited an IC50 of 231.7 µg/mL, achieving reduced toxicity than free bufalin. This study provides a novel approach on tailoring microspheres via the manipulation of membrane properties, facilitating the design and production of drug delivery system with desired properties for a wide range of purposes.

Preparation of Ropivacaine Encapsulated by Zeolite Imidazole Framework Microspheres as Sustained-Release System and Efficacy Evaluation.

The management of persistent postoperative pain still remains a clinical challenge currently. Although ropivacaine (RVC) is widely used for postoperative analgesia as a local anesthetic, the short half-life makes it difficult to achieve the desired duration of analgesia. Herein, a RVC sustained-release microspheres encapsulated by zeolite imidazole framework-8 (RVC@ZIF-8) was synthesized for the first time, which prolonged the sustained-release of RVC and decreased the resulting drug toxicity. RVC can continuously release in vitro for at least 96 h with high drug loading of 30.6 % and RVC@ZIF-8 had excellent biocompatibility and low cytotoxicity. In sciatic nerve block model, the sensory block time of RVC@ZIF-8 was significantly prolonged compared with RVC, achieving more than 72 h post injection and no inflammation or lesion were found. Based on high drug loading, ideal sustained-release and superior biological safety, RVC@ZIF-8 will be a novel delivery material for local anesthetic with potential application.

The inhibition mechanism and death mode of Microcystis aeruginosa induced by the continuous pressure of artemisinin sustained-release microspheres (ASMs)

Artemisinin, a natural allelochemical substance extracted from Artemisia annua, has been shown to have strong inhibitory effects on harmful cyanobacteria. However, only a few studies have systematically studied the mechanism of artemisinin in inhibiting algae and the process of algae cell death. In this study, the inhibition mechanism and death mode of M. aeruginosa under artemisinin sustained-release microspheres (ASMs) were investigated using a series of morphological, physiological and biochemical characteristics. The findings revealed that M. aeruginosa was significantly inhibited immediately after exposure to the 0.54 g·L−1 ASMs, with an inhibition rate (IR) exceeding 95 %, and the synthesis of phycobiliprotein and esterase activity were disturbed. In addition, ASMs exposure significantly increased caspase-3(-like) activities of M. aeruginosa. Under the continuous stress of ASMs, M. aeruginosa cells had three cell death modes: the first was necrosis-like cell death, which was characterized by cell wall rupture and leakage of cell contents; the second was apoptosis-like cell death, which was characterized by the disintegration of the cell structure, the integrity of the cell membrane, and the appearance of apoptotic bodies; and the last was autophagy-like cell death, which was characterized by cell swelling and appearance of autophagy vacuoles. These results indicated that ASMs could inhibit photosynthesis of M. aeruginosa cells, interfere with its antioxidant mechanisms and activate caspase-3(-like) activity, resulting in programmed cell death (PCD).

A Single Injection with Sustained-Release Microspheres and a Prime-Boost Injection of Bovine Serum Albumin Elicit the Same IgG Antibody Response in Mice

Although vaccination is still considered to be the cornerstone of public health care, the increase in vaccination coverage has stagnated for many diseases. Most of these vaccines require two or three doses to be administered across several months or years. Single-injection vaccine formulations are an effective method to overcome the logistical barrier to immunization that is posed by these multiple-injection schedules. Here, we developed subcutaneously (s.c.) injectable microspheres with a sustained release of the model antigen bovine serum albumin (BSA). The microspheres were composed of blends of two novel biodegradable multi-block copolymers consisting of amorphous, hydrophilic poly(ε-caprolactone)-poly(ethylene glycol)-poly(ε-caprolactone) (PCL-PEG-PCL) blocks and semi-crystalline poly(dioxanone) (PDO) blocks of different block sizes. In vitro studies demonstrated that the release of BSA could be tailored over a period of approximately four to nine weeks by changing the blend ratio of both polymers. Moreover, it was found that BSA remained structurally intact during release. Microspheres exhibiting sustained release of BSA for six weeks were selected for the in vivo study in mice. The induced BSA-specific IgG antibody titers increased up to four weeks after administration and were of the same magnitude as found in mice that received a priming and a booster dose of BSA in phosphate-buffered saline (PBS). Determination of the BSA concentration in plasma showed that in vivo release probably took place up to at least four weeks, although plasma concentrations peaked already one week after administration. The sustained-release microspheres might be a viable alternative to the conventional prime-boost immunization schedule, but a clinically relevant antigen should be incorporated to assess the full potential of these microspheres in practice.

Response of cytotoxin production ability to gene expression and cell molecular structure of Microcystis aeruginosa FACHB-905.

To investigate the inhibitory mechanism of artemisinin sustained-release microspheres (ASMs) on Microcystis aeruginosa (M. aeruginosa) from the molecular level, prx, psbA, fabZ, and mcyD were studied, and the cell death mode were also explored. The results showed that expression of prx was slightly up-regulated, while the expression of psbA, fabZ, and mcyD was significantly reduced. It can infer that oxidant damage and photic damage are the main mechanisms for the algicidal effect of ASMs on M. aeruginosa. It can be seen from the changes in cell morphology and structure that microspheres stress triggers apoptosis-like cell death, and the cell membrane is intact effectively preventing the leakage of microcystin-LR (MC-LR). Moreover, the down-regulation of mcyD gene also played major role in less extracellular MC-LR than intracellular MC-LR. It was concluded that the ASMs will not cause secondary ecological hazards while killing algae cells and have good application prospects.

Preliminary study on a novel biological scaffold loaded with Apelin-13 sustained-release microcapsules for promoting fallopian tube recanalization in rabbits.

Tubal factor infertility severely impairs the natural fertility of women, and there is for genuine tubal recanalization, including restoration of both the anatomy and function of the diseased fallopian tubes. Currently, there is no effective treatment available. This study aims to explore methods for promoting the repair and recanalization of fallopian tubes from these 2 aspects. Apelin-13 sustained-release microspheres and poly (lactic-co-glycolic acid) (PLGA) three-dimensional (3D) biodegradable scaffolds were prepared. The basic characteristics and in vivo degradation (mass loss rate) of the biodegradable scaffolds were tested, along with the in vitro drug release (cumulative release rate), the in vivo drug release (Apelin-13 plasma concentration), and in vitro degradation (degradation rate) of the microspheres. The Apelin-13 microspheres (microsphere group)/PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres (scaffold-microcapsule group) were injected/placed into the fallopian tubes of New Zealand rabbit of chronic salpingitis models. The patency, microscopic structure, and positive expression of estrogen receptor and progesterone receptor of the fallopian tubes in the control group, the model group, the microcapsule group, and the scaffold-microcapsule group was observed and compared. At the 4th week post-operation, the mass loss rate of the PLGA 3D scaffolds, the degradation rate of the microspheres, and the Apelin-13 sustained-release microspheres-generated cumulative release rate in vitro over 30 days were 98.66%, 70.58%, and 98.68% respectively. The plasma concentration of Apelin-13 reached its peak within 5 days and remained stable for 25 days. Compared with the model and microsphere groups, the scaffold-microsphere group showed a milder inflammatory reaction within the tubal lumen, a higher rate of fallopian tube patency, and higher expression levels of estrogen and progesterone receptors (all P<0.05). The indicators of the scaffold-microsphere group were close to those of the control group. The PLGA 3D scaffolds loaded with Apelin-13 sustained-release microspheres can comprehensively repair the anatomical structure and physiological function of the fallopian tubes and hold promise for truly effective tubal recanalization.

Integrated transcriptomic and metabolomic analysis of Microcystis aeruginosa exposed to artemisinin sustained-release microspheres.

Artemisinin sustained-release microspheres (ASMs) have been shown to inhibit Microcystis aeruginosa (M. aeruginosa) blooms. Previous studies have focused on inhibitory mechanism of ASMs on the physiological level of M. aeruginosa, but the algal inhibitory mechanism of ASMs has not been comprehensively and profoundly revealed. The study proposed to reveal the toxicity mechanism of ASMs on M. aeruginosa based on transcriptomics and metabolomics. After exposure to 0.2g·L-1 ASMs for 7 days, M. aeruginosa biomass was significantly inhibited, with an inhibition rate (IR) of 47% on day 7. Transcriptomic and metabolomic results showed that: (1) 478 differentially expressed genes (DEGs) and 251 differential metabolites (DMs) were obtained; (2) ASMs inhibited photosynthesis by blocking photosynthetic pigment synthesis, destroying photoreaction centers and photosynthetic carbon reactions; (3) ASMs reduced L-glutamic acid content and blocked glutathione (GSH) synthesis, leading to an imbalance in the antioxidant system; (4) ASM disrupted nitrogen metabolism and the hindered synthesis of various amino acids; (5) ASMs inhibited glyoxylate cycle and TCA cycle. This study provides an important prerequisite for the practical application of ASMs and a new perspective for the management of harmful algal blooms (HABs).

Ecotoxic side-effects of allelochemicals on submerged plant and its associated microfloras effectively relieved by sustained-release microspheres

Harmful algae bloom caused by water eutrophication is a burning question worldwide. Allelochemicals sustained-release microspheres (ACs-SMs) exhibited remarkable inhibition effect on algae, however, few studies have focused on the ecotoxic side-effects of ACs-SMs on submerged plant and its associated microfloras. Herein the effects of different exposure situations including single high-concentration ACs (15 mg/L, SH-ACs), repeated low-concentration ACs (3 × 5 mg/L, RL-ACs) and ACs-SMs containing 15 mg/L ACs on morphological indexes, chlorophyll content, lipid peroxidation, enzymatic activity, and chlorophyll fluorescence indexes of submerged plant Vallisneria natans and the richness and diversity of its associated microfloras (epibiotic microbes and sediment microbes) were studied. The results showed that pure ACs (RL-ACs and SH-ACs groups) had negative effects on plant height, mean leaf number and area of V. natans, but promoted the increase of mean leaf length. In addition, pure ACs caused lipid peroxidation, activated the antioxidant defense system, decreased chlorophyll content, and damaged photosynthetic system in leaves. Interestingly, ACs-SMs not only had barely negative effects on above indexes of V. natans, but had certain positive effects at the later experiment stage (days 50–60). Pure ACs and ACs-SMs all reduced the richness and diversity of microfloras in each group, and promoted the increase of relative abundance of dominant bacteria Pseudomonas, leading to a simpler community structure. Significantly, V. natans leaves diminished the effects of pure ACs and ACs-SMs on epibiotic microbes, and the plant rhizosphere was beneficial to the increase of dominant bacteria that promoted plant growth. Thus, sustained-release microspherification technology can effectively relieve the ecotoxic side-effects of pure ACs on submerged plant and its associated microfloras. This study fills the gap on the ecological safety knowledge of ACs-SMs and provides primary data for evaluating the feasibility and commercialization prospects of ACs-SMs as algae inhibitor in aquatic ecosystem.