Controlled Release Systems Research Articles

LGR5 as a Therapeutic Target of Antibody-Functionalized Biomimetic Magnetoliposomes for Colon Cancer Therapy.

The lack of specificity of conventional chemotherapy is one of the main difficulties to be solved in cancer therapy. Biomimetic magnetoliposomes are successful chemotherapy controlled-release systems, hyperthermia, and active targeting agents by functionalization of their surface with monoclonal antibodies. The membrane receptor Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) stands out as colorectal cancer (CRC) biomarker and appears to be related to treatment resistance and the development of metastasis. The aim of this study was to assess the effectiveness and safety of LGR5-targeted biomimetic magnetoliposomes loaded with oxaliplatin (OXA) or 5-fluorouracil (5-FU) in the selective treatment of CRC and their possible application in hyperthermia. Synthesis, characterization and determination of heating capacity of magnetoliposomes transporting OXA or 5-FU (with and without LGR5 functionalization) were conducted. In vitro antitumoral activity was assayed in multiple colorectal cell lines at different times of exposition. In addition to this, cell internalization was studied by Prussian Blue staining, flow cytometry and fluorescence microscopy. In vivo acute toxicity of magnetoliposomes was performed to evaluate iron-related toxicity. OXA and 5-FU loaded magnetoliposomes functionalized with LGR5 antibody showed higher cellular uptake than non-targeted nanoformulation with a reduction of the percentage of proliferation in colon cancer cell lines up to 3.2-fold of the IC50 value compared to that of free drug. The differences between non-targeted and targeted nanoformulations were more evident after short exposure times (4 and 8 hours). Interestingly, assays in the MC38 transduced cells with reduced LGR5 expression (MC38-L(-)), showed lower cell internalization of LGR5-targeted magnetoliposomes compared to non-transduced MC38 cell line. In addition, magnetoliposomes showed an in vitro favorable heating response under magnetic excitation and great iron-related biocompatibility data in vivo. Drug-loaded magnetoliposomes functionalized with anti-LGR5 antibodies could be a promising CRC treatment strategy for LGR5+ targeted chemotherapy, magnetic hyperthermia, and both in combination.

Fabrication of Rosuvastatin-Incorporated Polycaprolactone -Gelatin Scaffold for Bone Repair: A Preliminary In Vitro Study.

Rosuvastatin (RSV) is a hydrophilic, effective statin with a long half-life that stimulates bone regeneration. The present study aims to develop a new scaffold and controlled release system for RSV with favourable properties for bone tissue engineering (BTE). In this experimental study, high porous polycaprolactone (PCL)-gelatin scaffolds that contained different concentrations of RSV (0 mg/10 ml, 0.1 mg/10 ml, 0.5 mg/10 ml, 2.5 mg/10 ml, 12.5 mg/10 ml, and 62.5 mg/10 ml) were fabricated by the thermally-induced phase separation (TIPS) method. Mechanical and biological properties of the scaffolds were evaluated by Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), compressive strength, porosity, MTT, alkaline phosphatase (ALP) activity, water contact angle, degradation rate, pH alteration, blood clotting index (BCI), and hemocompatibility. SEM analysis confirmed that the porous structure of the scaffolds contained interconnected pores. FTIR results showed that the RSV structure was maintained during the scaffold's fabrication. RSV (up to 62.5 mg/10 ml) increased compressive strength (16.342 ± 1.79 MPa), wettability (70.2), and degradation rate of the scaffolds. Scaffolds that contained 2.5 mg/10 ml RSV had the best effect on the human umbilical cord mesenchymal stem cell (HUC-MSCs) survival, hemocompatibility, and BCI. As a sustained release system, only 31.68 ± 0.1% of RSV was released from the PCL-Gelatin-2.5 mg/10 ml RSV scaffold over 30 days. In addition, the results of ALP activity showed that RSV increased the osteogenic differentiation potential of the scaffolds. PCL-Gelatin-2.5 mg/10 ml RSV scaffolds have favorable mechanical, physical, and osteogenic properties for bone tissue and provide a favorable release system for RSV. They can mentioned as a a promising strategy for bone regeneration that should be further assessed in animals and clinical studies.

P116 Gastro-resistant microparticles for the oral delivery of Phycocyanin in the Inflammatory Bowel Disease therapy

Abstract Background Inflammatory Bowel Disease (IBD) is a chronically relapsing inflammation of the gastrointestinal tract, with ambiguous etiology. Oral route is the most common and acceptable approach for drug administration in the IBD treatment. However, it remains a challenge to maintain the stability of the drugs during oral treatment, particularly in the gastric environment, due its harsh conditions. In this context, the antioxidant and antiinflagmmatory properties of various natural compounds, as Phycocyanin (PC), a water-soluble bioactive molecule found in algae, can be strongly affected by factors as pH and temperature, inducing PC degradation and attenuating the curative effects. In this work, we produced a gastro-resistant microparticles (MPs) as controlled release systems for PC, and we aimed to compare its efficacy with free PC effects, on rat model of IBD. Methods The novel pharmaceutical system (SPC) was produced by microencapsulation technique, the spray-drying technique, using soy proteins (SPs) as natural excipients, aiming to improve the stability of the active ingredient and to ensure a modified release profile of PC. Rats were divided into groups and colitis was induced by intracolonic instillation of Dinitrobenzene sulfonic acid (DNBS, 20 mg/rat). Effects of preventive oral treatment of free PC or SPC were investigated, bioavailability was assessed and then body weight loss, stool consistency, colon weight/length index, myeloperoxidase activity (MPO), macroscopic damage and disease activity index (DAI) were determined. Results The SPC microparticle systems showed enhanced bioavailability of Phycocyanin, resulting in increased blood concentrations. The SPC system achieved the maximum AUC value and a modified release profile, particularly for gastro-resistant types, with a delayed Tmax of 5 hours, indicating their potential as a gastro-resistant formulation. Both PC and SPC pretreatments significantly ameliorated the severity of DNBS-induced colitis, however SPC pretreatment demonstrated enhanced activity vs PC. SPC rats showed a reduction of DAI, body weight loss and diarrhea incidence >15%, compared to PC (P<0.05); the ability of preventing the DNBS-induced macroscopic colonic damage and the MPO increase in SPC group were significantly higher than PC group (P<0.05) and also a tendency to improvement of colon weight/length index was observed. Conclusion In conclusion, the results of our research demonstrated that gastro-resistant microparticles (SPC) exhibit significantly improved therapeutic efficacy compared to orally administered free PC and can be developed as an effective new oral drug delivery system with controlled release profile in the treatment of IBD.

Gelatin extracted from chromium (III) tanned leather waste for the synthesis of controlled release hydrogel

Chromium (III) tanned leather wastes were used to obtain gelatin, which was applied as a coating material for the synthesis of controlled urea release hydrogels. It was found that the hydrogel released its total urea content in 120 h in aqueous solution and that it promoted a significant difference in the growth of arugula seedlings. When compared with commercial gelatin, the hydrogels based on gelatin extracted from tannery waste had similar behavior, especially in the way urea was diffused to the external environment of the controlled release system, it can be characterized as a material of non-Fickian behavior during the swelling process and later, as a Fickian behavior, when it begins its process of degradation of the polymer matrix. In this way, this work demonstrates that it is possible to value a waste to obtain tools to promote a more sustainable agriculture.

Engineering Degradation Rate of Polyphosphazene-Based Layer-by-Layer Polymer Coatings.

Degradable layer-by-layer (LbL) polymeric coatings have distinct advantages over traditional biomedical coatings due to their precision of assembly, versatile inclusion of bioactive molecules, and conformality to the complex architectures of implantable devices. However, controlling the degradation rate while achieving biocompatibility has remained a challenge. This work employs polyphosphazenes as promising candidates for film assembly due to their inherent biocompatibility, tunability of chemical composition, and the buffering capability of degradation products. The degradation of pyrrolidone-functionalized polyphosphazenes was monitored in solution, complexes and LbL coatings (with tannic acid), providing the first to our knowledge comparison of solution-state degradation to solid-state LbL degradation. In all cases, the rate of degradation accelerated in acidic conditions. Importantly, the tunability of the degradation rate of polyphosphazene-based LbL films was achieved by varying film assembly conditions. Specifically, by slightly increasing the ionization of tannic acid (near neutral pH), we introduce electrostatic "defects" to the hydrogen-bonded pairs that accelerate film degradation. Finally, we show that replacing the pyrrolidone side group with a carboxylic acid moiety greatly reduces the degradation rate of the LbL coatings. In practical applications, these coatings have the versatility to serve as biocompatible platforms for various biomedical applications and controlled release systems.

A Controlled Release Aptasensor Utilizing AIE-Active MOFs as High-Efficiency ECL Nanoprobe for the Sensitive Detection of Adenosine Triphosphate.

Improving the sensitivity in electrochemiluminescence (ECL) detection systems necessitates the integration of robust ECL luminophores and efficient signal transduction. In this study, we report a novel ECL nanoprobe (Zr-MOF) that exhibits strong and stable emission by incorporating aggregation-induced emission ligands into Zr-based metal-organic frameworks (MOFs). Meanwhile, we designed a high-performance signal modulator through the implementation of a well-designed controlled release system with a self-on/off function. ZnS quantum dots (QDs) encapsulated within the cavities of aminated mesoporous silica nanoparticles (NH2-SiO2) serve as the ECL quenchers, while adenosine triphosphate (ATP) aptamers adsorbed on the surface of NH2-SiO2 through electrostatic interaction act as "gatekeepers." Based on the target-triggered ECL resonance energy transfer between Zr-MOF and ZnS QDs, we establish a coreactant-free ECL aptasensor for the sensitive detection of ATP, achieving an impressive low detection limit of 0.033 nM. This study not only demonstrates the successful combination of ECL with controlled release strategies but also opens new avenues for developing highly efficient MOFs-based ECL systems.

Development of a Nanoparticle System for Controlled Release in Bioprinted Respiratory Scaffolds.

The use of nanoparticle systems for the controlled release of growth factors is a promising approach to mimicking of the biochemical environment of native tissues in tissue engineering. However, sustaining growth factor release inside an appropriate therapeutic window is a challenge, particularly in bioprinted scaffolds. In this study, a chitosan-coated alginate-based nanoparticle system loaded with hepatocyte growth factor was developed and then incorporated into bioprinted scaffolds. The release kinetics were investigated with a focus on identifying the impact of the chitosan coating and culture conditions. Our results demonstrated that the chitosan coating decreased the release rate and lessened the initial burst release, while culturing in dynamic conditions had no significant impact compared to static conditions. The nanoparticles were then incorporated into bioinks at various concentrations, and scaffolds with a three-dimensional (3D) structure were bioprinted from the bioinks containing human pulmonary fibroblasts and bronchial epithelial cells to investigate the potential use of a controlled release system in respiratory tissue engineering. It was found that the bioink loaded with a concentration of 4 µg/mL of nanoparticles had better printability compared to other concentrations, while the mechanical stability of the scaffolds was maintained over a 14-day culture period. The examination of the incorporated cells demonstrated a high degree of viability and proliferation with visualization of the beginning of an epithelial barrier layer. Taken together, this study demonstrates that a chitosan-coated alginate-based nanoparticle system allows the sustained release of growth factors in bioprinted respiratory tissue scaffolds.

Anti-Candida activity and in vitro toxicity screening of antifungals complexed with β-cyclodextrin.

The emergence of resistant fungal species and the toxicity of currently available antifungal drugs are relevant issues that require special consideration. Cyclodextrins inclusion complexes could optimize the antimicrobial activity of such drugs and create a controlled release system with few side effects. This study aimed to assess the in vitro toxicity and antifungal effectiveness of nystatin (Nys) and chlorhexidine (Chx) complexed or not with β-cyclodextrin (βCD). First, a drug toxicity screening was performed through the Artemia salina bioassay. Then, the minimum inhibitory concentrations (MICs) against Candida albicans were determined with the broth microdilution test. After MICs determination, the cytotoxicity of the drugs was evaluated through the methyl-thiazolyl-tetrazolium (MTT) and neutral red (NR) assays and through cell morphology analysis. The PROBIT analysis was used to determine the median lethal concentration (LC50), and the cell viability values were submitted to one-way analysis of variance(ANOVA)/Tukey (α = 0.05). Overall, the βCD-complexed antifungals were less toxic against A.salina than their raw forms, suggesting that inclusion complexes can reduce the toxicity of drugs. The MICs obtained were as follows: Nys 0.5mg/L; Nys:βCD 4mg/L; Chx 4mg/L; and Chx:βCD 8mg/L. Chx showed significant cytotoxicity (MTT: 12.9 ± 9.6%; NR: 10.6 ± 12.5%) and promoted important morphological changes. Cells exposed to the other drugs showed viability above 70% with no cellular damage. These results suggest that antifungals complexed with βCD might be a biocompatible option for the treatment of Candida-related infections.

Minoxidil delivered via a stem cell membrane delivery controlled release system promotes hair growth in C57BL/6J mice.

Objective: Umbilical cord-derived mesenchymal stem cell membrane-loaded minoxidil (MXD) nanoparticles (STCM-MXD-NPs) were prepared to investigate their effects on hair growth in C57BL/6J mice. Methods: STCM-MXD-NPs were obtained by freeze-thawing and differential centrifugation, and their effects on hair growth were evaluated using C57BL/6J mice. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF-1) were detected by real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Protein expression levels of marker of proliferation Ki-67 (MKI67) and β-catenin (CTNNB) in skin tissue were detected by immunohistochemistry. Results: STCM-MXD-NPs improved MXD solubility. They released the drug slowly, increasing its transdermal properties, accumulation in the skin, and content in the hair bulb tissues with a better efficacy than that of ordinary MXD. Moreover, STCM-MXD-NPs significantly upregulated the mRNA and protein levels of VEGF and IGF-1 and promoted the protein expression of MKI67 and CTNNB in mouse skin tissues, promoting mouse hair growth. Conclusion: Stem cell membrane-loaded MXD nanoparticles with slow-release properties increased MXD accumulation in the skin by improving its transdermal properties, increasing VEGF, IGF-1, MKI67, and CTNNB expression levels and promoting hair growth in C57BL/6J mice.

Development and evaluation of ciprofloxacin local controlled release materials based on molecularly imprinted polymers

The aim of this study was the molecular imprinting polymers (MIPs) assessment as a controlled release system of ciprofloxacin. The MIPs synthesis was performed by three different methods: emulsion, bulk, and co-precipitation. Lactic acid (LA) and methacrylic acid (MA) were used as functional monomers and ethylene glycol dimethacrylate as crosslinker. Also, nonimprinted polymers (NIPs) were synthesized. MIPs and NIPs were characterized by scanning electron microscopy, Fourier Transform Infrared Reflection, specific surface area, pore size, and release kinetics. Their efficiency against Staphylococcus aureus and Escherichia coli, and their cytotoxicity in dermal fibroblast cells were proven. Results show that MIPs are mesoporous materials with a pore size between 10 and 20 nm. A higher adsorption with the co-precipitation MIP with MA as a monomer was found. The release kinetics proved that a non-Fickian process occurred and that the co-precipitation MIP with LA presented the highest release rate (90.51 mg/L) in 8 h. The minimum inhibitory concentration was found between 0.031 and 0.016 mg/L for Staphylococcus aureus and between 0.004 and 0.031 mg/L for the Escherichia coli. No cytotoxicity in cellular cultures was found; also, cellular growth was favored. This study demonstrated that MIPs present promising properties for drug administration and their application in clinical practice.

Recent advances in stimuli-responsive controlled release systems for neuromodulation.

Neuromodulation aims to modulate the signaling activity of neurons or neural networks by the precise delivery of electrical stimuli or chemical agents and is crucial for understanding brain function and treating brain disorders. Conventional approaches, such as direct physical stimulation through electrical or acoustic methods, confront challenges stemming from their invasive nature, dependency on wired power sources, and unstable therapeutic outcomes. The emergence of stimulus-responsive delivery systems harbors the potential to revolutionize neuromodulation strategies through the precise and controlled release of neurochemicals in a specific brain region. This review comprehensively examines the biological barriers controlled release systems may encounter in vivo and the recent advances and applications of these systems in neuromodulation. We elucidate the intricate interplay between the molecular structure of delivery systems and response mechanisms to furnish insights for material selection and design. Additionally, the review contemplates the prospects and challenges associated with these systems in neuromodulation. The overarching objective is to propel the application of neuromodulation technology in analyzing brain functions, treating brain disorders, and providing insightful perspectives for exploiting new systems for biomedical applications.

Prospective study of pain levels when using controlled-release dinoprostone vaginal delivery system (PROPESS) compared with mechanical methods in pregnant women requiring cervical ripening

Prospective study of pain levels when using controlled-release dinoprostone vaginal delivery system (PROPESS) compared with mechanical methods in pregnant women requiring cervical ripening

Novel pH-sensitive of organic composite (kc-g-poly(AAc-co-AAm)/bentonite), synthesis and characterization candidate as a carrier for controlled release system in vitro to some drugs

Novel pH-sensitive of organic composite (kc-g-poly(AAc-co-AAm)/bentonite), synthesis and characterization candidate as a carrier for controlled release system in vitro to some drugs

Enhancing Sustainability in Agriculture: Natural Polymer-Based Controlled Release Systems for Effective Pest Management and Environmental Protection

Enhancing Sustainability in Agriculture: Natural Polymer-Based Controlled Release Systems for Effective Pest Management and Environmental Protection

Anti-Tumor Mechanism of Ropivacaine and Application of Controlled Release System

Anti-Tumor Mechanism of Ropivacaine and Application of Controlled Release System

Colorimetric sensing for the sensitive detection of UO22+via the phosphorylation functionalized mesoporous silica-based controlled release system.

In this study, we developed a simple and sensitive colorimetric sensing method for the detection of UO22+, which was built to release MB from the molybdenum disulfide with a phosphate group (MoS2-PO4) gated mesoporous silica nanoparticles functionalized phosphate group (MSN-PO4) with UO22+ chelating. In the presence of UO22+, MoS2-PO4 can be effectively adsorbed onto the surface of MSN-PO4 based on the coordination chemistry for strong affinity between the P-O bond and UO22+. The adsorbed MoS2-PO4 was then utilized as an ideal gate material to control the release of signal molecules (MB) entrapped within the pores of MSN-PO4, resulting in a detectable decrease in the absorption peak at 663 nm. This colorimetric sensing demonstrated the advantages of simplicity and easy manipulation and exhibited a linear response to the concentration of UO22+ within the range of 0.02-0.2 μM. The detection limit of UO22+ was determined to be 0.85 nM, which was lower than the limit (130 nmol L-1) set by the US Environmental Protection Agency. Furthermore, the proposed colorimetric sensing method has been utilized to determine UO22+ in samples of Xiangjiang River and tap water, and a high recovery rate was achieved. This method shows promising potential in preventing and controlling environmental pollution.

Chitosan- A Promising agent for site specific drug delivery in periodontics

Periodontal diseases are chronic infectious illnesses that have become a significant burden on oral health. Several new treatment targets have been found because of advances in the study of the epidemiology, aetiology, and pathophysiology of periodontitis, as well as the analysis of the polymicrobial interaction in the oral bacterial communities. Efforts to limit growth of bacteria and the formation of substances that eventually damage the tissues supporting the teeth have been the foundation of periodontal therapy. Systemic antibiotic administration for periodontitis has significant shortcomings, attracting attentiontowards the advancement of localized drug delivery systems capable ofmaintaining effective antibiotic concentrations at the intended site throughout the course of treatment with minimum side effects. A controlled release system that can be placed within the periodontal pocket so as to extend therapeutic concentrations at the desired site at a considerably lesser dosage is a pressing priority. Chitosan, a potential carbohydrate biopolymer, is receiving scientific interest in a diverse range of biomedical fields due to its exceptional chemical and pharmacokinetic attributes. Chitosan is a biocompatible and biodegradable naturally occurring polysaccharide with several uses in dentistry owing to its functional versatility and easy accessibility. The applications of chitosan are vast, exciting, and still unexplored. Thisreviewfocusesonthe potential uses of chitosan in periodontology.

Synthesis and characterization of zinc ion-integrated quercetin delivery system using areca nut seeds nanocellulose

This research introduces an innovative approach utilizing waste-derived cellulose from areca nut seeds. A novel quercetin-loaded cellulose nanofiber (CNF-Zn-QT) composite was synthesized by integrating zinc ions into a cellulose nanofiber-quercetin complex. With a high loading capacity (17.48%) and encapsulation efficiency (90.42%), the optimized CNF-Zn-QT composite exhibited superior antioxidant activity against DPPH and ABTS+ radicals compared to quercetin alone. Furthermore, the CNF-Zn-QT composite demonstrated a slower in vitro release rate of quercetin, indicating its potential for sustained release applications. Notably, the composite also displayed enhanced antibacterial properties, attributed to the antibacterial nature of zinc ions. In terms of storage, the CNF-Zn-QT composite outperformed the CNF-QT composite in stability, underscoring its promise for long-term applications. This research not only offers a novel perspective on the utilization of areca nut seeds waste but also emphasizes the multifunctional capabilities of the CNF-Zn-QT composite, making it a promising candidate for various applications, including antioxidant and antibacterial products, controlled release systems, and stable storage solutions.

Preparation of a novel alginate hydrogel microspheres covered by hollow silica for controlled-release application

Sodium alginate hydrogel has been widely used in the field of controlled-release. In this paper, in order to prevent the negative effect of fast degradation and explosive release of pure sodium alginate hydrogel in the drug delivery process, we developed a novel alginate hydrogel supported by hollow silica microsphere for drug delivery. Briefly, the drugs were fused with sodium alginate and the hollow silica microspheres followed by ion crosslinking to form a composite hydrogel microsphere with a core–shell structure (SA@SiO2). The structure and morphology of the composite hydrogel were characterized by Fourier infrared spectroscopy (FT-IR), thermogravimetric analysis (TG), scanning electron microscope (SEM), transmission electron microscope (TEM) along with fluorescence microscope. On this basis, using three different types of organic compounds (rhodamine B, Indocyanine green and salicylic acid) as model molecules, the controlled-release performance of the SA@SiO2 microspheres were investigated in detail. The research results show that the drug delivery system has broad-spectrum controlled-release performance for different types of molecules, and the controlled-release time can exceed 40 h. At the same time, the pH- responsive property of the sodium alginate hydrogel endows the delivery system with a certain targeting function. This study provides a new strategy for constructing an efficient targeted drug controlled-release system.

Chitosan-Grafted-Poly(N-vinylcaprolactam)-Decorated Fe3O4@SiO2 Core-Shell Nanoformulation as an Efficient Drug Delivery System for Poorly Soluble Drugs.

Hydrocortisone, a commonly used anti-inflammatory drug, has limited aqueous solubility and several side effects. To address this challenge, as a proof-of-concept, this article demonstrates the development of a controlled-release drug delivery system (DDS) for hydrocortisone using chitosan-grafted poly(N-vinylcaprolactam) (CS-g-PNVCL)-coated core-shell Fe3O4@SiO2 nanoformulations (NFs). Reported magnetic nanoparticles (NPs) were synthesized and modified with silica, PNVCL, and CS precursors to enhance the biocompatibility of DDS and drug-loading efficiency. The release rate of hydrocortisone from Fe3O4@SiO2@CS-g-PNVCL NFs was observed to be higher at lower pH values, and the smart polymer coating demonstrated temperature responsiveness, facilitating drug release at higher temperatures. Fe3O4@SiO2@CS-g-PNVCL NFs exhibited a cell viability of around 97.2 to 87.3% (5-100 μg/mL) after 24-48 h, while the hydrocortisone-NFs had a cell viability of around 93.2 to 82.3%. Our findings suggest that CS-g-PNVCL-coated Fe3O4@SiO2 NPs effectively enhance the solubility, loading capacity, and targeted delivery of poorly soluble drugs, thereby improving their therapeutic efficacy and bioavailability.