Search Results (16)

Nanoparticles, especially gold nanoparticles (Au NPs) have gained increasing interest in biomedical applications. Used for disease prevention, diagnosis and therapies, its significant advantages in therapeutic efficacy and safety have been the main target of interest. Its application in immune system prevention, stability in physiological environments and cell membranes, low toxicity and optimal bioperformances are critical to the success of engineered nanomaterials. Its unique optical properties are great attractors. Recently, several physical and chemical methods for coating these NPs have been widely used. Biomolecules such as DNA, RNA, peptides, antibodies, proteins, carbohydrates and biopolymers, among others, have been widely used in coatings of Au NPs for various biomedical applications, thus increasing their biocompatibility while maintaining their biological functions. This review mainly presents a general and representative view of the different types of coatings and Au NP functionalization using various biomolecules, strategies and functionalization mechanisms. Full article

The pharmaceutical industry has faced significant changes in recent years, primarily influenced by regulatory standards, market competition, and the need to accelerate drug development. Model-informed drug development (MIDD) leverages quantitative computational models to facilitate decision-making processes. This approach sheds light on the complex interplay between the influence of a drug’s performance and the resulting clinical outcomes. This comprehensive review aims to explain the mechanisms that control the dissolution and/or release of drugs and their subsequent permeation through biological membranes. Furthermore, the importance of simulating these processes through a variety of in silico models is emphasized. Advanced compartmental absorption models provide an analytical framework to understand the kinetics of transit, dissolution, and absorption associated with orally administered drugs. In contrast, for topical and transdermal drug delivery systems, the prediction of drug permeation is predominantly based on quantitative structure–permeation relationships and molecular dynamics simulations. This review describes a variety of modeling strategies, ranging from mechanistic to empirical equations, and highlights the growing importance of state-of-the-art tools such as artificial intelligence, as well as advanced imaging and spectroscopic techniques. Full article

“Green” strategies to build up novel organic nanocarriers with bioperformance are modern trends in nanotechnology. In this way, the valorization of bio-wastes and the use of living systems to develop multifunctional organic and biogenic nanocarriers (OBNs) have revolutionized the nanotechnological and biomedical fields. This paper is a comprehensive review related to OBNs for bioactives’ delivery, providing an overview of the reports on the past two decades. In the first part, several classes of bioactive compounds and their therapeutic role are briefly presented. A broad section is dedicated to the main categories of organic and biogenic nanocarriers. The major challenges regarding the eco-design and the fate of OBNs are suggested to overcome some toxicity-related drawbacks. Future directions and opportunities, and finding “green” solutions for solving the problems related to nanocarriers, are outlined in the final of this paper. We believe that through this review, we will capture the attention of the readers and will open new perspectives for new solutions/ideas for the discovery of more efficient and “green” ways in developing novel bioperformant nanocarriers for transporting bioactive agents. Full article

Biphasic in vitro dissolution testing is an attractive approach to reflect on the interplay between drug dissolution and absorption for predicting the bioperformance of drug products. The purpose of this study was to investigate the in vivo relevance of a biphasic dissolution test for the immediate release (IR) formulations of a Biopharmaceutics Classification System (BCS) Class II drug, lamotrigine (LTG). The biphasic dissolution test was performed using USP apparatus II with the dual paddle modification. A level A in vitro-in vivo correlation (IVIVC) was constructed between the in vitro partition into the octanol and absorption data of the reference product. A good relation between in vitro data and absorption was obtained (r² = 0.881). The one-compartment open model was introduced to predict the human plasma profiles of the test product. The generic product was found to be bioequivalent to the original product in terms of 80–125% bioequivalence (BE) criteria (85.9–107% for the area under the plasma concentration curve (AUC) and 82.7–97.6% for the peak plasma concentration (C_max) with a 90% confidence interval (CI)). Overall, it was revealed that the biphasic dissolution test offers a promising ability to estimate the in vivo performance of IR formulations of LTG, providing considerable time and cost savings in the development of generic drug products. Full article

Coatings are an attractive and challenging selection for improving the bioperformance of metallic devices. Composite materials based on bioglass/antibiotic/polymer are herein proposed as multifunctional thin films for hard tissue implants. We deposited a thin layer of the polymeric material by matrix-assisted pulsed laser evaporation—MAPLE onto Ti substrates. A second layer consisting of bioglass + antibiotic was applied by MAPLE onto the initial thin film. The antimicrobial activity of MAPLE-deposited thin films was evaluated on Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, and Pseudomonas aeruginosa standard strains. The biocompatibility of obtained thin films was assessed on mouse osteoblast-like cells. The results of our study revealed that the laser-deposited coatings are biocompatible and resistant to microbial colonization and biofilm formation. Accordingly, they can be considered viable candidates for biomedical devices and contact surfaces that would otherwise be amenable to contact transmission. Full article

Fish bones are a natural calcium phosphate (CaP) sources used in biomaterials production for bone regeneration. CaP scaffolds can be enriched with other substances with biological activity to improve bone repair. This study aimed to evaluate the physicochemical properties and bone regeneration potential of biphasic calcium phosphate (BCP) scaffolds impregnated with free curcumin (BCP-CL) or complexed with β-cyclodextrin (BCP-CD) compared to BCP scaffolds. Rietveld’s refinement showed that BCP is composed of 57.2% of HAp and 42.8% of β-TCP and the molar ratio of Ca/P corresponds to 1.59. The scaffolds presented porosity (macro and microporosity) of 57.21%. Apatite formation occurred on the BCP, BCP-CL, and BCP-CD surface, in vitro, in SBF. Micro-Raman technique showed a reduction in the dissolution rate of β-TCP in the curcumin-impregnated scaffolds over time, and in vivo studies on critical-size defects, in rat calvaria, had no additional regenerative effect of BCP-CL and BCP-CD scaffolds, compared to BCP scaffolds. Despite this, the study showed that curcumin impregnation in BCP scaffolds prolongs the release of the β-TCP phase, the BCP- phase with the higher osteoinductive potential, representing an advantage in tissue engineering. Full article

Bacillus thuringiensis is a microorganism used for the production of biopesticides worldwide. In the present paper, different kinetic models were analyzed to study and compare three different strains of Bt ssp kurstaki (LIP, BLB1, and HD1). Bioperformances (vegetative cell, spore, substrate, and protein) and successive culture phases (oxidative growth, limitation and sporulation, and protein release) were depicted with an overarching aim to estimate total protein productivity, yield, and titer. In the end, two models were calibrated using experimental dataset (11 batches culture in 3 L bioreactor with semisynthetic medium), subsequently validated, and statistically compared. Both models satisfactorily followed the dynamics of the experimental data. Finally, a dynamic model was selected following the Akaike information criterion (AIC). Full article

The research presented herein follows an urgent global need for the development of novel surface engineering techniques that would allow the fabrication of next-generation cardiovascular stents, which would drastically reduce cardiovascular diseases (CVD). The combination of hydrothermal treatment (HT) and treatment with highly reactive oxygen plasma (P) allowed for the formation of an oxygen-rich nanostructured surface. The morphology, surface roughness, chemical composition and wettability of the newly prepared oxide layer on the Ti substrate were characterized by scanning electron microscopy (SEM) with energy-dispersive X-ray analysis (EDX), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and water contact angle (WCA) analysis. The alteration of surface characteristics influenced the material’s bio-performance; platelet aggregation and activation was reduced on surfaces treated by hydrothermal treatment, as well as after plasma treatment. Moreover, it was shown that surfaces treated by both treatment procedures (HT and P) promoted the adhesion and proliferation of vascular endothelial cells, while at the same time inhibiting the adhesion and proliferation of vascular smooth muscle cells. The combination of both techniques presents a novel approach for the fabrication of vascular implants, with superior characteristics. Full article

Presently, a large number of drug molecules in development are BCS class II or IV compounds with poor aqueous solubility. Various novel solubilization techniques have been used to enhance drug solubility. Among them, amorphous solid dispersions (ASD), which convert a crystalline drug into an amorphous mixture of drug and polymer, have been demonstrated to be an effective tool in enhancing drug solubility and bioavailability. There are multiple ways to produce amorphous solid dispersions. The goal of the present study is to investigate two commonly used processing methods, hot-melt extrusion (HME) and spray drying, and their impact on drug bioperformance. The amorphous solid dispersions of a model compound, posaconazole (25% drug loading) in HPMCAS-MF, were successfully manufactured via the two processing routes, and the physicochemical properties, in vitro and in vivo performance of the resulting ASDs were characterized and compared. It was found that in vitro drug release of the ASDs from two-stage dissolution was significantly different. However, the two ASDs showed similar in vivo performance based on cynomolgus monkey PK studies. A mechanistic understanding of the in vitro and in vivo behaviors of the solid dispersions was discussed. Full article

This study focuses on the development of biocompatible oil-in-water (O/W) nanoemulsions based on polyglycerol esters, as promising carriers for natural actives: red raspberry seed oil—RO and hydro-glycolic fruit extracts from red raspberry—RE and French oak—FE. Nanoemulsions were obtained via phase inversion composition (PIC) method at room temperature by dilution of microemulsion phase, confirmed by visual appearance, percentage of transmittance, microscopic, rheological and differential scanning calorimetry (DSC) investigations. The results have shown that the basic RO-loaded formulation could be further enriched with hydro-glycolic fruit extracts from red raspberry or French oak, while keeping a semi-transparent appearance due to the fine droplet size (Z-ave: 50 to 70 nm, PDI value ≤ 0.1). The highest antioxidant activity (~92% inhibition of the DPPH radical) was achieved in the formulation containing both lipophilic (RO) and hydrophilic antioxidants (FE), due to their synergistic effect. The nanoemulsion carrier significantly increased the selective cytotoxic effect of RO towards malignant melanoma (Fem-X) cells, compared to normal human keratinocytes (HaCaT). In vivo study on human volunteers showed satisfactory safety profiles and significant improvement in skin hydration during 2 h after application for all nanoemulsions. Therefore, polyglycerol ester-based nanoemulsions can be promoted as effective carriers for red raspberry seed oil and/or hydro-glycolic fruit extracts in topical formulations intended for skin protection and hydration. Full article

Albendazole (ABZ) and benznidazole (BZL) are drugs with low solubility used in parasitic infections treatment. In this research, solid dispersion (SD) technology was used to enhance ABZ and BZL performance by increasing their dissolution rate and solubility. SDs were prepared by the fusion method, employing Poloxamer 407 (P407) as carrier to disperse 32 of BZL or 50% w/w of ABZ. Furthermore, physical mixtures (PM) of P407 and either ABZ or BZL were also prepared, and then SDs and PMs were characterized. Dissolution tests of SDs, PMs and commercial formulations (CF) of ABZ and BZL were carried out and dissolution profiles were analyzed with the lumped mathematical model, which allowed parameters of pharmaceutical relevance to be obtained. The results indicated that ABZ SD presented an initial dissolution rate (IDR) 21-fold and 11-fold faster than PM and CF, respectively, while the IDR of BZL SD was 2.5-fold and 4.5-fold faster than PM and CF, respectively. For BZL formulations, the time required to reach 80% dissolution of the drug (t_80%) was 4 (SD), 46 (PM), and 239 min (CF), while the dissolution efficiency (DE) at 30 min was 85 (DS), 71 (MF) and 65% (FC). For ABZ formulations, t_80% was 2 (SD), value not reached (PM) and 40 min (CF), while the DE at 30 min was 85 (SD), 36 (MF) and 65% (CF). The SDs developed notably increased the dissolution rate, in consonance with the values obtained from the pharmaceutical parameters, which could lead to faster absorption and, consequently, increase the bioavailability of these drugs. Full article

The objective of the present study is the valorization of natural resources and the recycling of vegetal wastes by converting them into novel plasmonic bio-active hybrids. Thus, a “green” approach was used to design pectin-coated bio-nanosilver. Silver nanoparticles were generated from two common garden herbs (Mentha piperita and Amaranthus retroflexus), and pectin was extracted from lemon peels. The samples were characterized by the following methods: Ultraviolet–visible (UV-Vis) absorption spectroscopy, Fourier Transform Infrared (FT-IR), X-ray Diffraction (XRD), X-ray Photoelectron Spectroscopy (XPS), dynamic light scattering (DLS), Atomic Force Microscopy (AFM), Scanning Electron Microscopy (SEM)–Energy-dispersive X-ray Spectroscopy (EDX), and zeta potential measurements. Microscopic investigations revealed the spherical shape and the nano-scale size of the prepared biohybrids. Their bioperformances were checked in terms of antioxidant and antibacterial activity. The developed plasmonic materials exhibited a strong ability to scavenge short-life (96.1% ÷ 98.7%) and long-life (39.1% ÷ 91%) free radicals. Microbiological analyses demonstrated an impressive antibacterial effectiveness of pectin-based hybrids against Escherichia coli. The results are promising, and the obtained biomaterials could be used in many bio-applications, especially as antioxidant and antimicrobial biocoatings. Full article

Crystallization alters the characteristics of TiO₂ nanosurfaces, which consequently influences their bio-performance. In various biomedical applications, the anatase or rutile crystal phase is preferred over amorphous TiO₂. The most common crystallization technique is annealing in a conventional furnace. Methods such as hydrothermal or room temperature crystallization, as well as plasma electrolytic oxidation (PEO) and other plasma-induced crystallization techniques, present more feasible and rapid alternatives for crystal phase initiation or transition between anatase and rutile phases. With oxygen plasma treatment, it is possible to achieve an anatase or rutile crystal phase in a few seconds, depending on the plasma conditions. This review article aims to address different crystallization techniques on nanostructured TiO₂ surfaces and the influence of crystal phase on biological response. The emphasis is given to electrochemically anodized nanotube arrays and their interaction with the biological environment. A short overview of the most commonly employed medical devices made of titanium and its alloys is presented and discussed. Full article

The present paper aims atincreasing the bioperformance of implantable Ti50Zr alloy using zwitterionic cysteine drug coating. Aspects such as stability, biocompatibility, and antibacterial effects were investigated with the help of various methods such as infrared spectroscopy (FT-IR), scanning electronic microscopy (SEM), electrochemical methods, contact angle determinations and cell response. The experimental data of zwitterionic cysteine coating indicate the existence of a hydration layer due to hydrophilic groups evidenced in FT-IR which is responsible for the decrease of contact angle and antibacterial capabilities. The electrochemical stability was evaluatedbased on Tafel plots and electrochemical impedance spectroscopy (EIS). The cell response to cysteine was determined with gingival fibroblasts measuring lactate dehydrogenase (LDH) activity, concentrations of nitric oxide (NO) and intracellular level of reactive oxygen species (ROS). All experimental results supported the increase of stability and better cells response of implantable Ti50Zr alloy coated with zwitterionic cysteine drug. The antibacterial index was measured against Staphylococcus aureus and Escherichia coli. It was demonstrated that the coating enhanced the production of intracellular ROS in time, which subsequently caused a significant increase in antibacterial index. Full article

The development of a weakly basic compound is often challenging due to changes in pH that the drug experiences throughout the gastrointestinal tract. As the drug transitions from the low pH of the stomach to the higher pH of the small intestine, drug solubility decreases. A stomach with a higher pH, caused by food or achlorhydric conditions brought about by certain medications, decreases even the initial solubility. This decreased drug solubility is reflected in lower in vivo exposures. In many cases, a solubility-enabling approach is needed to counteract the effect of gastrointestinal pH changes. Solid dispersions of amorphous drug in a polymer matrix have been demonstrated to be an effective tool to enhance bioavailability, with the potential to mitigate the food and achlorhydric effects frequently observed with conventional formulations. Because solid dispersions are in a metastable state, they are particularly sensitive to processing routes that may control particle attributes, stability, drug release profile, and bioperformance. A better understanding of the impacts of processing routes on the solid dispersion properties will not only enhance our ability to control the product properties, but also lower development risks. In this study, a weakly basic compound with greatly reduced solubility in higher pHs was incorporated into a solid dispersion via both spray drying and hot melt extrusion. The properties of the solid dispersion via these two processing routes were compared, and the impact on dissolution behavior and in vivo performance of the dispersions was investigated. Full article