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Biomedicine & Pharmacotherapy =... Aug 2023In the present study, 5-fluorouracil-loaded niosomal nanoparticles were successfully prepared and coated with chitosan and subsequently crosslinked by tripolyphosphate...
In the present study, 5-fluorouracil-loaded niosomal nanoparticles were successfully prepared and coated with chitosan and subsequently crosslinked by tripolyphosphate to form niosomal nanogels. The prepared niosomal formulations were fully characterized for their particle size, zeta potential, particle morphology, drug entrapment efficiency, and in vitro drug release profile. The prepared niosomal nanocarriers exhibited nanoscale particle sizes of 165.35 ± 2.75-322.85 ± 2.75 nm. Chitosan-coated and TPP-crosslinked niosomes exhibited a slightly decreased in particle size and a switch of zeta potential from negative to positive values. In addition, high yield percentage, drug encapsulation efficiency, and drug loading values of 92.11 ± 2.07 %, 66.59 ± 6.06, and 4.65 ± 0.5 were obtained for chitosan-coated formulations, respectively. Moreover, lowering the rate of 5-FU in vitro release was achieved within 72 h by using chitosan-coated formulations. All prepared formulations revealed hemocompatible properties in hemolysis assay with less than 5 % hemolysis percentage at their higher possible concentrations (500 µM and 1 mM). The cell viability by MTT assay showed higher anticancer activity against B16F10 cancerous cells and lower cytotoxicity toward NIH3T3 normal cells than control and pure 5-FU in the studied concentration range (10-100 µM). Investigating the cell migration inhibition properties of fabricated formulations revealed similar results with in vitro cell viability assay with a higher migration inhibition rate for B16F10 cells than NIH3T3 cells, controls, and free 5-FU.
Topics: Mice; Animals; Chitosan; Nanogels; Delayed-Action Preparations; Drug Carriers; Hemolysis; NIH 3T3 Cells; Fluorouracil; Antimetabolites; Nanoparticles; Hydrogen-Ion Concentration; Particle Size
PubMed: 37267634
DOI: 10.1016/j.biopha.2023.114943 -
Drug Delivery Dec 2023Messenger RNA (mRNA) has become one of the most potential drugs in recent years. However, efficient and safe delivery of fragile and easily degradable mRNA is a major...
Messenger RNA (mRNA) has become one of the most potential drugs in recent years. However, efficient and safe delivery of fragile and easily degradable mRNA is a major challenge. Appropriate delivery system (DS) determines the final effect of mRNA. Cationic lipids play a crucial and decisive role in the entire DS, but also cause huge biosafety problems due to the high toxicity. In this study, a new DS for mRNA delivery that combines negatively charged phospholipids was developed in order to neutralize the positive charge and thus increase the safety. Further, the factors affecting mRNA transfection from cell to animal were investigated. The mRNA DS with optimum condition of lipid composition, proportions, structure, and transfection time was synthesized. Adding an appropriate amount of the anionic lipid to liposomes could increase the safety while maintaining the original transfection efficiency. For transporting mRNA in vivo, requirements regarding the mRNA encapsulation and releasing rate should be further considered to optimize DS design and preparation.
Topics: Animals; Liposomes; Phospholipids; Transfection; Biological Transport; RNA, Messenger
PubMed: 37309122
DOI: 10.1080/10717544.2023.2219869 -
ACS Applied Bio Materials Jan 2024Current pharmacological and surgical therapies for the central nervous system (CNS) show a limited capacity to reduce the damage progression; that together with the... (Review)
Review
Current pharmacological and surgical therapies for the central nervous system (CNS) show a limited capacity to reduce the damage progression; that together with the intrinsic limited capability of the CNS to regenerate greatly reduces the hopes of recovery. Among all the therapies proposed, the tissue engineering strategies supplemented with therapeutic stem cells remain the most promising. Neural tissue engineering strategies are based on the development of devices presenting optimal physical, chemical, and mechanical properties which, once inserted in the injured site, can support therapeutic cells, limiting the effect of a hostile environment and supporting regenerative processes. Thus, this review focuses on the employment of hydrogel and nanofibrous scaffolds supplemented with stem cells as promising therapeutic tools for the central and peripheral nervous systems in preclinical and clinical applications.
Topics: Biocompatible Materials; Tissue Engineering; Cell- and Tissue-Based Therapy; Central Nervous System; Hydrogels
PubMed: 38158393
DOI: 10.1021/acsabm.3c01058 -
Drug Design, Development and Therapy 2024Research for tumor treatment with significant therapy effects and minimal side-effects has been widely carried over the past few decades. Different drug forms have... (Review)
Review
Research for tumor treatment with significant therapy effects and minimal side-effects has been widely carried over the past few decades. Different drug forms have received a lot of attention. However, systemic biodistribution induces efficacy and safety issues. Intratumoral delivery of agents might overcome these problems because of its abundant tumor accumulation and retention, thereby reducing side effects. Delivering hydrogels, nanoparticles, microneedles, and microspheres drug carriers directly to tumors can realize not only targeted tumor therapy but also low side-effects. Furthermore, intratumoral administration has been integrated with treatment strategies such as chemotherapy, enhancing radiotherapy, immunotherapy, phototherapy, magnetic fluid hyperthermia, and multimodal therapy. Some of these strategies are ongoing clinical trials or applied clinically. However, many barriers hinder it from being an ideal and widely used option, such as decreased drug penetration impeded by collagen fibers of a tumor, drug squeezed out by high density and high pressure, mature intratumoral injection technique. In this review, we systematically discuss intratumoral delivery of different drug carriers and current development of intratumoral therapy strategies.
Topics: Humans; Neoplasms; Drug Delivery Systems; Antineoplastic Agents; Animals; Drug Carriers; Nanoparticles
PubMed: 38882051
DOI: 10.2147/DDDT.S467835 -
International Journal of Biological... Sep 2023Hydrocolloids are important ingredients in food formulations and their modification can lead to novel ingredients with unique functionalities beyond their nutritional... (Review)
Review
Hydrocolloids are important ingredients in food formulations and their modification can lead to novel ingredients with unique functionalities beyond their nutritional value. Cold plasma is a promising technology for the modification of food biopolymers due to its non-toxic and eco-friendly nature. This review discusses the recent published studies on the effects of cold plasma treatment on non-starch hydrocolloids and their derivatives. It covers the common phenomena that occur during plasma treatment, including ionization, etching effect, surface modification, and ashing effect, and how they contribute to various changes in food biopolymers. The effects of plasma treatment on important properties such as color, crystallinity, chemical structure, rheological behavior, and thermal properties of non-starch hydrocolloids and their derivatives are also discussed. In addition, this review highlights the potential of cold plasma treatment to enhance the functionality of food biopolymers and improve the quality of food products. The mechanisms underlying the effects of plasma treatment on food biopolymers, which can be useful for future research in this area, are also discussed. Overall, this review paper presents a comprehensive overview of the current knowledge in the field of cold plasma treatment of non-starch hydrocolloids and their derivatives and highlights the areas that require further investigation.
Topics: Plasma Gases; Polysaccharides; Colloids; Biopolymers; Food
PubMed: 37543265
DOI: 10.1016/j.ijbiomac.2023.126098 -
Microcapsules and Nanoliposomes Based Strategies to Improve the Stability of Blueberry Anthocyanins.Molecules (Basel, Switzerland) Oct 2023Blueberry anthocyanins are water-soluble natural pigments that can be used as both natural antioxidants and natural colorants. However, their structural instability...
Blueberry anthocyanins are water-soluble natural pigments that can be used as both natural antioxidants and natural colorants. However, their structural instability greatly limits their application in the food, pharmaceutical, and cosmetic industries. In this study, blueberry anthocyanin microcapsules (BAM) and blueberry anthocyanin liposomes (BAL) were fabricated based on blueberry anthocyanins. Film dispersion methods were used to prepare the BAL. Their preparation processes were optimized and compared to improve the stability of the blueberry anthocyanins following exposure to light and high temperatures. The BAM were prepared through complex phase emulsification. The blueberry anthocyanins were protected by the shell materials composed of sodium alginate after being formed into BAM. Under the optimal conditions, the embedding rate of BAM and BAL can reach as high as 96.14% and 81.26%, respectively. In addition, the particle size, zeta potential, microtopography, and structure feature information of the BAM and BAL were compared. The average particle sizes of the BAM and BAL were 9.78 μm and 290.2 nm, respectively, measured using a laser particle size analyzer, and the zeta potentials of the BAM and BAL were 34.46 mV and 43.0 mV, respectively. In addition, the optimal preparation processes were determined through single-factor and response surface optimization experiments. The most important factors in the single-factor experiment for the preparation of microcapsules and liposomes were the content of CaCl and the amount of anthocyanin. The preservation rates in the light and dark were also compared, and the thermal stabilities of the BAM and BAL were characterized through differential thermal scanning. The results showed that both the BAM and BAL maintained the stability of blueberry anthocyanins, and no significant difference was found between the indices used to evaluate their stability. The results of this study provide theoretical support for the development of effective systems to maintain the stability of anthocyanins, thereby improving their bioavailability after ingestion by humans.
Topics: Humans; Blueberry Plants; Anthocyanins; Liposomes; Capsules; Fruit
PubMed: 37959763
DOI: 10.3390/molecules28217344 -
PloS One 2023Rheumatoid arthritis is considered a chronic systemic autoimmune disorder that may cause joint destruction. Triptolide, an active component isolated from Tripterygium...
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.
Topics: Humans; Delayed-Action Preparations; Microspheres; Particle Size; Arthritis, Rheumatoid
PubMed: 37856525
DOI: 10.1371/journal.pone.0292861 -
International Journal of Pharmaceutics Jul 2023Through 3D printing (3DP), many parameters of solid oral dosage forms can be customised, allowing for truly personalised medicine in a way that traditional...
Through 3D printing (3DP), many parameters of solid oral dosage forms can be customised, allowing for truly personalised medicine in a way that traditional pharmaceutical manufacturing would struggle to achieve. One of the many options for customisation involves dose titration, allowing for gradual weaning of a medication at dose intervals smaller than what is available commercially. In this study we demonstrate the high accuracy and precision of 3DP dose titration of caffeine, selected due to its global prevalence as a behavioural drug and well-known titration-dependent adverse reactions in humans. This was achieved using a simple filament base of polyvinyl alcohol, glycerol, and starch, utilising hot melt extrusion coupled with fused deposition modelling 3DP. Tablets containing 25 mg, 50 mg, and 100 mg doses of caffeine were successfully printed with drug content in the accepted range prescribed for conventional tablets (90 - 110%), and excellent precision whereby the weights of all doses showed a relative standard deviation of no more than 3%. Importantly, these results proved 3D printed tablets to be far superior to splitting a commercially available caffeine tablet. Additional assessment of filament and tablet samples were reviewed by differential scanning calorimetry, thermogravimetric analysis, HPLC, and scanning electron microscopy, showing no evidence of degradation of caffeine or the raw materials, with smooth and consistent filament extrusion. Upon dissolution, all tablets achieved greater than 70% release between 50 and 60 min, showing a predictable rapid release profile regardless of dose. The outcomes of this study highlight the benefits that dose titration with 3DP can offer, especially to more commonly prescribed medications that can have even more harmful withdrawal-induced adverse reactions.
Topics: Humans; Caffeine; Tablets; Polyvinyl Alcohol; Hot Melt Extrusion Technology; Printing, Three-Dimensional; Drug Liberation; Technology, Pharmaceutical
PubMed: 37315638
DOI: 10.1016/j.ijpharm.2023.123132 -
Protein Science : a Publication of the... Mar 2024Interactions between membrane proteins (MPs) and lipid bilayers are critical for many cellular functions. In the Rosetta molecular modeling suite, the implicit membrane...
Interactions between membrane proteins (MPs) and lipid bilayers are critical for many cellular functions. In the Rosetta molecular modeling suite, the implicit membrane energy function is based on a "slab" model, which represent the membrane as a flat bilayer. However, in nature membranes often have a curvature that is important for function and/or stability. Even more prevalent, in structural biology research MPs are reconstituted in model membrane systems such as micelles, bicelles, nanodiscs, or liposomes. Thus, we have modified the existing membrane energy potentials within the RosettaMP framework to allow users to model MPs in different membrane geometries. We show that these modifications can be utilized in core applications within Rosetta such as structure refinement, protein-protein docking, and protein design. For MP structures found in curved membranes, refining these structures in curved, implicit membranes produces higher quality models with structures closer to experimentally determined structures. For MP systems embedded in multiple membranes, representing both membranes results in more favorable scores compared to only representing one of the membranes. Modeling MPs in geometries mimicking the membrane model system used in structure determination can improve model quality and model discrimination.
Topics: Membrane Proteins; Liposomes; Lipid Bilayers; Models, Molecular; Micelles
PubMed: 38358133
DOI: 10.1002/pro.4908 -
Journal of Materials Science. Materials... Nov 2023Ophthalmologists have used hyaluronan (HA) products as adjuncts to ocular surgery since the 1970s. However, HA products are not always functional in surgeries of the...
Ophthalmologists have used hyaluronan (HA) products as adjuncts to ocular surgery since the 1970s. However, HA products are not always functional in surgeries of the posterior eye segment due to their lack of biomechanical strength. In this study, we developed an in situ crosslinked HA (XL-HA) and evaluated its potential as an adjunct to vitrectomy surgery in an in vitro model with a triamcinolone acetonide (TA) layer used as a pseudo residual vitreous cortex (RVC). Within a few minutes at concentrations over 0.9%, XL-HA, generated by the click chemistry of HA-dibenzocyclooctyne and HA-azidoethylamine, formed a hydrogel with the appropriate hardness for tweezers peeling. XL-HA (concentration, 0.76-1.73%) without dispersion successfully entered the TA layer and removed more than 45% of the total TA. Dynamic viscoelasticity helps to explain the rheological behavior of hydrogels, and the assessment results for XL-HA indicated that suitable concentrations were between 0.97% and 1.30%. For example, 1.30% XL-HA hydrogel reached sufficient hardness at 3 min for tweezers peeling, and the TA removal ability exceeded 70%. These results demonstrated that XL-HA was a potential adjunct to successful vitrectomy.
Topics: Hyaluronic Acid; Vitrectomy; Hardness; Hydrogels; Ophthalmology
PubMed: 37930485
DOI: 10.1007/s10856-023-06757-9