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Objective:Using atenolol as a model drug,the aim of this study was to develop a sustained and controlled transdermal drug delivery system(TDDS)based on polyethyleneimine-modified MoS2 nanoparticles(PEI-MoS2 NPs)that were responsive to near infrared(NIR)laser irradiation.Methods:The three-dimensional flower-like PEI-MoS2 NPs were successfully synthesized and further characterized by attenuated total reflection Fourier transform infrared spectroscopy,X-ray diffraction measurements,scanning electron microscopy,and transmission electron microscopy.The controlled release capacity of PEI-MoS2 NPs was examined using in vitro drug release and skin penetration experiments.Results:The PEI-MoS2 NPs exhibited a drug loading efficiency of 53.86% and high photothermal conversion ability.Moreover,the release of atenolol was enhanced by NIR stimulation with an enhancement ratio of 1.56.Conclusion:NIR-controlled PEI-MoS2 NPs was essential for the control and sustained release of drugs in TDDS.
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Controlled-release fertilizers have been increasingly used. This study aimed to evaluate and adapt new technologies applied via soil for sustainable coffee production, in order to generate information that contribute to the technical innovation of the crop for the Vale do Ribeira region. The experiment was set at UNESP, in Registro SP. The experimental design was in randomized blocks. The experiment consisted of eight treatments with four replications, with plots of six plants. Four doses (200, 300, 400 and 500 kg ha-1) of a mixed fertilizer 20-05-20 were used, with controlled release in six months, intended for coffee trees in formation and production, compared to the dose of 500 kg ha-1 of the conventional mixed fertilizer 20-05-20, ammonium sulfate and calcium nitrate with boron, in addition to a control treatment, which did not receive NPK fertilization. The cultivar used was 'Obatã IAC 1669' in 3.0 x 0.6 m spacing. The following characteristics were evaluated: number of plagiotropic branches, number of nodes of plagiotropic branches, stem diameter, plant height and yield, in two harvest periods, besides the surface chemical characteristic of the soil. Increasing the dose of the slow-release fertilizer leads to greater plant growth; the coffee plant presents a highly responsive behavior to the increase in fertilizer doses in relation to nitrogen, and the use of the slow-release fertilizer Agroblen (20-05-20) 100% and ammonium sulfate + SS + KCl allows greater yield.
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Objective: The present research work is focused to develop in situ raft gel of lafutidine. Sodium alginate is one of the critical components for the development in situ raft system.Methods: The formulation was prepared using hydrophilic polymers such as ethyl cellulose, HPMC K4M, and chitosan. The formulations were subjected to evaluation characteristics such as pH, in vitro gelling time, viscosity, density, gel strength, drug-polymer compatibility studies, drug content floating lag time, swelling index, and in vitro release studies.Results: The pH of all the prepared batches was found in the range of 5.7 to 7.6. All the prepared formulations showed viscosity in the range of 264 to 320 cps, with gelling time from 4-7 s. For F1-F15 batches Floating lag time was found to be in the range of 9-24 sec. Densities of all formulations stomach specific in situ gels were in the range of 0.4 to 0.8 gm/cm3. The highest swelling index was observed in F15 with 14.16% Highest gel strength is exhibited by F15; all the formulations were in the range of 95.46–99.95, indicating the uniform distribution of the drug. Formulation F15 containing chitosan in combination with ethyl cellulose gave the highest drug release of 99.78% and also showed sustained and controlled release for up to 24h.Conclusion: F15 shows an R2 value of 0.999. As its value is nearer to the ‘1’ it is confirmed as it follows the Zero order release with an ‘n’ value is 1.5021 for the optimized formulation (F15) i.e., the n value indicates super case II transport and is considered as optimized formulation.
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@#In order to mask the bitterness of azithromycin (AZI) and individually regulate the drug release rate to reduce gastrointestinal irritation, immediate-release AZI-AmberliteTM IRP64/HPC and delayed-release AZI-AmberliteTM IRP69/RS100 were prepared by modifying with hydroxypropyl cellulose (HPC) and Eudragit RS100, respectively, and further combined to achieve controlled release.The drug loading and drug utilization rate of AZI-ion exchange resin complexes were measured; the structure of AZI-ion exchange resin complexes was characterized by differential scanning calorimetry and X-ray diffraction; and the wetting humidity, odor masking effects, in vitro dissolution and release behaviors were determined.The results showed that the formation of AZI-ion exchange resin complexes changed the original crystallization state of the drug, that the 2.5% HPC-modified AZI-AmberliteTM IRP64/HPC and the 0.5% RS100-modified AZI-AmberliteTM IRP69/RS100 demonstrated good taste masking effect, and that their combination in the drug content ratio of 13∶67 achieved the expected drug release behavior, i.e.rapid release of AZI in the first 10 min and smooth release in the later 6 h.These results indicated that the AZI-ion exchange resin complexes prepared by surface modification and their composites could mask the bitterness of AZI and realize the flexible adjustment of drug release rate, which lays the foundation for the research and development of new AZI preparations.
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The application of intraocular drug delivery is usually limited due to special anatomical and physiological barriers, and the elimination mechanisms in the eye. Organic nano-drug delivery carriers exhibit excellent adhesion, permeability, targeted modification and controlled release abilities to overcome the obstacles and improve the efficiency of drug delivery and bioavailability. Solid lipid nanoparticles can entrap the active components in the lipid structure to improve the stability of drugs and reduce the production cost. Liposomes can transport hydrophobic or hydrophilic molecules, including small molecules, proteins and nucleic acids. Compared with linear macromolecules, dendrimers have a regular structure and well-defined molecular mass and size, which can precisely control the molecular shape and functional groups. Degradable polymer materials endow nano-delivery systems a variety of size, potential, morphology and other characteristics, which enable controlled release of drugs and are easy to modify with a variety of ligands and functional molecules. Organic biomimetic nanocarriers are highly optimized through evolution of natural particles, showing better biocompatibility and lower toxicity. In this article, we summarize the advantages of organic nanocarriers in overcoming multiple barriers and improving the bioavailability of drugs, and highlight the latest research progresses on the application of organic nanocarriers for treatment of ocular diseases.
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Drug Carriers , Delayed-Action Preparations , Drug Delivery Systems , Nanoparticles/chemistryABSTRACT
In the research on cancer theranostics, most environment-sensitive drug delivery systems can only achieve unidirectional and irreversible responsive changes under pathological conditions, thereby improving the targeting effect and drug release performance of the delivery system. However, such irreversible changes pose potential safety hazards when the dynamically distributed delivery system returns to the blood circulation or transports to the normal physiological environment. Intelligent reversible drug delivery systems can respond to normal physiological and pathological microenvironments to achieve bidirectional and reversible structural changes. This feature will help to precisely control the drug release of the delivery system, prolong the blood circulation time, improve the targeting efficiency, and avoid the potential safety hazards of the irreversible drug delivery system. In this review, we describe the research progress of intelligent reversible drug delivery system from two main aspects: controlled drug release and prolonged blood circulation time/enhanced cellular internalization of drug.
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Objective To evaluate the release characteristics in vitro, pharmacokinetics in rabbits and in vivo-in vitro correlation of silymarin phospholipid complex microporous osmotic pump controlled release tablets（SM-PC MPOP）. Methods The release characteristics of SM-PC MPOP in vitro were detected by HPLC in the artificial gastric fluid. Six beagle dogs were subjected to double cycle cross control, which were given SM-PC MPOP and Legalon（30 mg/kg）. The concentration of silybin in plasma was determined by HPLC and the data were processed by software. Results The cumulative release rate of SM-PC MPOP in vitro was over 85% in 12 h. The pharmacokinetics in beagle dogs showed that SM-PC MPOP and legalon conformed to double compartment first-order absorption model and the pharmacokinetic parameters were obtained: tmax:（3.2±0.4）and（0.9±0.1）h, Cmax:（0.298 6±0.068 9）and（0.629 9±0.076 5）μg/ml, AUC0→24:（2.996 8±0.583 3）and（2.268 9±0.432 8）h·μg /ml. The relative bioavailability of SM-PC MPOP was（162.21 ± 30.82）%. Conclusion SM-PC MPOP could release slowly, which could increase the relative bioavailability significantly. The correlation between the absorption in vivo and release in vitro was fine（r = 0.839 0）.
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Aim To develop an UPLC-MS/MS method to determine the concentration of lorcaserin hydrochloride in beagle plasma, and study the pharmacokinetics of osmotic pump controlled-release tablets of lorcaserin hydrochloride. Methods A randomized crossover design was used, carbamazepine as the internal standard(IS), and plasma protein precipitation with acetonitrile. The chromatographic was Phenomenex Polar C18 column(100 mm×2. 1 mm, 3 μm), and acetonitrile - water(containing 10 mmol·L-1 ammonium acetate and 0.1% formic acid)(40:60, V/V)was mobile phase. Multiple reaction monitoring mode and electrospray positive ionization were used to detect lorcaserin hydrochloride. The MS/MS ion transitions were monitored at m/z 196.2→129.2 for lorcaserin hydrochloride and m/z 237→194.1 for carbamazepine, respectively. Results The linear range was 1 to 500 μg·L-1(r=0.999 2), the extraction recovery rate ranged from 87.70% to 89.70%, the precision RSD was 9.7%. The accuracy and matrix effect met the requirements, and the stability of lorcaserin hydrochloride was good in -20 ℃ refrigerator for 45 d, repeated freezing and thawing for three times, placed at room temperature for 24 h, and the disposed samples placed in automatsampler for 6 h were stable. The main pharmacokinetic parameters of the controlled-release tablet and immediate-release tablet were as follows:Tmax was(8.00±1.27)h and(1.00±0.13)h, Cmax was(70.56±3.73)μg·L-1 and(176.33±16.73)μg·L-1, and AUC0-t was(966.33±7.56)μg·h·L-1 and(973.05±69.09)μg·h·L-1, respectively. Conclusions The established UPLC-MS/MS method can be used to study the pharmacokinetics of lorcaserin hydrochloride in the plasma of beagle dogs, and osmotic pump controlled-release tablets has sustained release effect.
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This research aims to investigate the encapsulation and controlled release effect of the newly developed self-assembling peptide R-LIFE-1 on exosomes. The gelling ability and morphological structure of the chiral self-assembling peptide (CSAP) hydrogel were examined using advanced imaging techniques, including atomic force microscopy, transmission electron microscopy, and cryo-scanning electron microscopy. The biocompatibility of the CSAP hydrogel was assessed through optical microscopy and fluorescent staining. Exosomes were isolated via ultrafiltration, and their quality was evaluated using Western blot analysis, nanoparticle tracking analysis, and transmission electron microscopy. The controlled release effect of the CSAP hydrogel on exosomes was quantitatively analyzed using laser confocal microscopy and a BCA assay kit. The results revealed that the self-assembling peptide R-LIFE-1 exhibited spontaneous assembly in the presence of various ions, leading to the formation of nanofibers. These nanofibers were cross-linked, giving rise to a robust nanofiber network structure, which further underwent cross-linking to generate a laminated membrane structure. The nanofibers possessed a large surface area, allowing them to encapsulate a substantial number of water molecules, thereby forming a hydrogel material with high water content. This hydrogel served as a stable spatial scaffold and loading matrix for the three-dimensional culture of cells, as well as the encapsulation and controlled release of exosomes. Importantly, R-LIFE-1 demonstrated excellent biocompatibility, preserving the growth of cells and the biological activity of exosomes. It rapidly formed a three-dimensional network scaffold, enabling the stable loading of cells and exosomes, while exhibiting favorable biocompatibility and reduced cytotoxicity. In conclusion, the findings of this study support the notion that R-LIFE-1 holds significant promise as an ideal tissue engineering material for tissue repair applications.
Subject(s)
Exosomes , Delayed-Action Preparations , Hydrogels , Microscopy, Electron, Scanning , PeptidesABSTRACT
Polysialic acid(PSA)is a homopolymer consisting of N-acetylneuraminic monomers linked by α-2,8 and(or)α-2,9 glucoside bonds.As an endogenous polysaccharide,PSA has good biocompatibility,biodegradability,high hydrophilicity,non-immunogenicity,long-term circulation,easy modification and specific targeting to selectins.In the field of drug delivery research,PSA not only can be connected with small molecule drugs,active peptides or proteins,but also can be grafted or electrostatic cross-linked with polymers to build a variety of drug delivery systems,such as nanogels,polymer micelles,liposomes,etc.It has shown great potential value in the treatment of various disease models such as tumors,inflammatory diseases and neurological diseases.In this paper,the biological functions of PSA,the classification of drug delivery systems based on PSA and its application progress were reviewed,in order to provide reference for further application and research of PSA.
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Neovascularization is the hallmark of many fundus diseases, including diabetic retinopathy, retinal vein occlusion and neovascular age-related macular degeneration.More and more evidence suggests that vascular endothelial growth factor (VEGF) plays a critical role in neovascularization.Anti-VEGF drugs are the first-line treatment for neovascular fundus diseases and have achieved significant results.However, there are drawbacks such as short drug half-lives and the need for long-term administration to maintain effective concentrations, which increases the economic burden and medical risk for patients and reduces compliance.Therefore, finding a new method for intraocular drug delivery is of great clinical importance.Based on the principle that diabetes patients use insulin pumps to gradually release drugs, the ocular anti-VEGF drug delivery system can continuously release anti-VEGF drugs over a period of time, significantly reducing the injection frequency and improving patient compliance.At present, the research on ocular anti-VEGF drug delivery systems is still immature, and various systems are in different stages of clinical trials.According to different design principles, they can be divided into three categories with their characteristics, micropump (extraocular storage delivery systems), biodegradable implants, and non-biodegradable implants.This article summarized and analyzed the controlled ocular anti-VEGF drug release delivery systems currently in clinical trials.
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Maize has a high nutritional requirement, especially regarding NPK fertilization. However, conventional fertilization with these nutrients presents a high loss potential, mainly by volatilization, leaching, adsorption, and fixation, which may reflect on the development and yield of maize plants. Using fertilizers with increased efficiency seeks to mitigate these limitations, reducing potential losses due to gradual nutrient release. This study aimed to compare the nutrition, growth, and production of maize plants subjected to different doses and special NPK fertilizers fully applied at planting and their residual effect on the soil. It was a randomized block design in a 3x4 factorial scheme with four replications. The first factor consisted of conventional mineral, polymer-coated, and organomineral + PGPB fertilizers. The second factor included doses of 0, 60, 90, and 120 kg ha-¹ of NPK. The study evaluated vegetative growth, foliar nutrition (N, P, and K), yield growth components, productivity, profitability, and residual K content in the soil after cultivation. The conventional mineral fertilizer produced more dry biomass in the aerial part. Profitability was similar between conventional and special fertilizers. However, the latter performed better overall in vegetative and productive growth, showing a potential reduction of the applied doses without compromising grain yield, especially in organomineral + PGPB fertilization. This treatment also presented a higher residual effect of K on the soil.
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Diabetes mellitus is a major health problem with increasing prevalence at a global level. The discovery of insulin in the early 1900s represented a major breakthrough in diabetes management, with further milestones being subsequently achieved with the identification of glucagon-like peptide-1 (GLP-1) and the introduction of GLP-1 receptor agonists (GLP-1 RAs) in clinical practice. Moreover, the subcutaneous delivery of biotherapeutics is a well-established route of administration generally preferred over the intravenous route due to better patient compliance and prolonged drug absorption. However, current subcutaneous formulations of GLP-1 RAs present pharmacokinetic problems that lead to adverse reactions and treatment discontinuation. In this review, we discuss the current challenges of subcutaneous administration of peptide-based therapeutics and provide an overview of the formulations available for the different routes of administration with improved bioavailability and reduced frequency of administration.
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The bone formation promoter recombinant human parathyroid hormone 1-34 [PTH (1-34)] has a short half-life and low bioavailability. In this study, we prepared a biodegradable and temperature-sensitive hyaluronic acid-poly-N-isopropyl acrylamide (AHA-g-PNIPAAm), and further investigated its effects of PTH (1-34) release and cell behavior as drug carrier. The structure of AHA-g-PNIPAAM was confirmed by hydrogen nuclear magnetic resonance spectroscopy and infrared spectroscopy. Next, PTH (1-34) loaded thermo-sensitive hydrogels were prepared by physical swelling method and their stability was investigated. The morphology of hydrogel was observed by scanning electron microscope. The minimum critical transition temperature and drug release behavior of hydrogels were investigated by ultraviolet spectrophotometry. The tetrazolium-based colorimetric assay (MTT assay) was used to investigate the toxicity and proliferation effects of PTH (1-34)-loaded thermo-sensitive hydrogel on mouse mononuclear macrophage RAW264.7 and mouse precranial osteoblasts MC3T3-E1. The effect of PTH (1-34)-loaded thermo-sensitive hydrogel on the differentiation of RAW264.7 was investigated by the tartrate-resistant acid phosphatase assay. The results showed that the PTH (1-34)-loaded thermo-sensitive hydrogel prepared in this study displayed regular three-dimensional honeycomb structure, and had good stability, thermo-sensitivity and sustained and controlled release properties, which could promote the proliferation of MC3T3-E1 cells more effectively and inhibit the differentiation of RAW264.7 into osteoclasts.
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@#Introduction: Nowadays the use of synthetic polymers has become an integral part of modern medicine. Poly(2-hydroxyethyl methacrylate) has attracted special attention for therapeutic use. The objective of this study was to develop novel polymeric material based on poly(2-hydroxyethyl methacrylate) by addition of water as pore-forming agent and antimicrobial components, which would differ from similar materials by controlled release of active substances. Methods: The antimicrobial release kinetics study materials were immersed into distilled water followed by sampling and measuring their concentration. Concentration of chlorhexidine bigluconate and metronidazole was determined using spectrophotometric method and decamethoxine by photocolorimetric method based on reaction with eosin. The swelling rate was determined by gravimetric method. Results: Conventional dressing materials, after being soaked with antiseptic solutions, have demonstrated limited abilities in releasing active substances. Gauze pads were found to release antimicrobials during a short period of time reaching 50–80 % for decamethoxine containing samples and almost 100 % for those with metronidazole and chlorhexidine bigluconate at 2 h of observation. No study active substances were released from activated charcoal dressings. Similar results were obtained with porcine xenografts. Unlike the above mentioned dressing materials, modified polymer matrix based on poly(2-hydroxyethyl methacrylate) showed the controlled release of antimicrobial substances into water medium. Study material containing 3.0 % of decamethoxine and 76.3 % of water demonstrated optimal efficiency in the rate and duration of release, exerting high physical and mechanical properties. Conclusion: The synthesized polymers are similar to conventional dressings in antimicrobial release kinetics, but in some characteristics they are better for practical application.
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Objective To observe the clinical efficacy and safety of nifedipine controlled-release tablets on the antihypertensive effect of hypertensive patients under high altitude environment. Methods 42 hypertensive inpatients in the 940th hospital (altitude 1500 ) were set to the plain hypertension group, and 42 cases of hypertensive inpatients in Bayi hospital (altitude 3800 m) were set to the plateau hypertension group. Both groups of patients were given nifedipine controlled-release tablets 30 mg daily, taken orally in the morning for 6 consecutive days. Monitor blood pressure and heart rate three times a day to compare the clinical efficacy and occurrence of adverse drug reactions in the two groups. Results After treatment, the total effective rates of the high-altitude hypertension group and the plain hypertension group were 47.62% (20 cases/42 cases) and 76.19% (32 cases/42 cases) respectively with no statistical difference (P<0.05). The adverse drug reactions of the two groups of patients were tachycardia and palpitations. The incidence of total adverse drug reactions in the high-altitude hypertension group and the plain hypertension group were 14.29% and 11.90% respectively with no statistical difference (P>0.05). Conclusion The high-altitude hypoxic environment could affect the antihypertensive effect of nifedipine controlled-release tablets, which could not control the patient's blood pressure effectively in the short term.
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Abstract The current research focused on screening and finding the significant independent variables in stavudine loaded tablet, followed by optimizing the best formulation using central composite design. The objective of the study to develop stavudine loaded controlled release tablet utilizing reduced factorial design, followed by optimization technique as well as characterization of prepared tablets. Preliminary trial batches were prepared using different grades of hydroxypropyl methylcellulose. The resolution-IV reduced factorial design was selected to screen the significant independent variables in the dosage form design. A total number of eight runs were prepared and responses were recorded. The signified factors identified by half-normal and Pareto chart. The prepared tablets are evaluated for various physiochemical characterizations. Three dependent responses such as hardness, dissolution at 6 hour and 12 hours are considered in optimization process. Later on, drug-polymer interaction study was carried out. The principal of the study design based on finding the best formulation with prefixed set parameter values utilizing the concept of screening technique. It observed that HPMC K15M (57.18 %), HPMC K100 (66.32 %) and PVP K30 (7.97 %) as best composition in a formulation batch would fulfill the predetermined parameter with specific values.
Subject(s)
Stavudine/administration & dosage , Process Optimization , Hypromellose Derivatives/classification , Drug Liberation , Tablets/administration & dosage , Pharmaceutical Preparations/analysisABSTRACT
BACKGROUND: Super-paramagnetic iron oxide nanoparticles (SPION) contain a chemotherapeutic drug and are regarded as a promising technique for improving targeted delivery into cancer cells. RESULTS: In this study, the fabrication of 5-fluorouracil (5-FU) was investigated with loaded Dextran (DEXSPION) using the co-precipitation technique and conjugated by folate (FA). These nanoparticles (NPs) were employed as carriers and anticancer compounds against liver cancer cells in vitro. Structural, magnetic, morphological characterization, size, and drug loading activities of the obtained FA-DEX-5-FUSPION NPs were checked using FTIR, VSM, FESEM, TEM, DLS, and zeta potential techniques. The cellular toxicity effect of FA-DEX-5-FU-SPION NPs was evaluated using the MTT test on liver cancer (SNU-423) and healthy cells (LO2). Furthermore, the apoptosis measurement and the expression levels of NF-1, Her-2/neu, c-Raf-1, and Wnt-1 genes were evaluated post-treatment using flow cytometry and RT-PCR, respectively. The obtained NPs were spherical with a suitable dispersity without noticeable aggregation. The size of the NPs, polydispersity, and zeta were 74 ± 13 nm, 0.080 and 45 mV, respectively. The results of the encapsulation efficiency of the nano-compound showed highly colloidal stability and proper drug maintenance. The results indicated that FA-DEX-5-FU-SPION demonstrated a sustained release profile of 5-FU in both phosphate and citrate buffer solutions separately, with higher cytotoxicity against SNU-423 cells than against other cells types. These findings suggest that FA-DEX-SPION NPs exert synergistic effects for targeting intracellular delivery of 5-FU, apoptosis induction, and gene expression stimulation. CONCLUSIONS: The findings proved that FA-DEX-5-FU-SPION presented remarkable antitumor properties; no adverse subsequences were revealed against normal cells.
Subject(s)
Humans , Carcinoma, Hepatocellular/drug therapy , Fluorouracil/administration & dosage , Liver Neoplasms/drug therapy , Polymers , Gene Expression/drug effects , Drug Delivery Systems , Apoptosis/drug effects , Reverse Transcriptase Polymerase Chain Reaction , Delayed-Action Preparations , Nanoparticles/administration & dosage , Magnetite Nanoparticles , Flow CytometryABSTRACT
Insulin therapy plays an essential role in the treatment of diabetes mellitus. However, frequent injections required to effectively control the glycemic levels lead to substantial inconvenience and low patient compliance. In order to improve insulin delivery, many efforts have been made, such as developing the nanoparticles (NPs)-based release systems and oral insulin. Although some improvements have been achieved, the ultimate results are still unsatisfying and none of insulin-loaded NPs systems have been approved for clinical use so far. Recently, nano‒protein interactions and protein corona formation have drawn much attention due to their negative influence on the
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Localized delivery, comparing to systemic drug administration, offers a unique alternative to enhance efficacy, lower dosage, and minimize systemic tissue toxicity by releasing therapeutics locally and specifically to the site of interests. Herein, a localized drug delivery platform ("plum‒pudding" structure) with controlled release and long-acting features is developed through an injectable hydrogel ("pudding") crosslinked