Properties Of Drug Carriers Research Articles

Construction of a pectin/sodium alginate composite hydrogel delivery system for improving the bioaccessibility of phycocyanin

In this study, different concentrations of sodium alginate were compounded with pectin and phycocyanin to co-prepare composite hydrogel spheres (HP-PC-SA 0.2 %, 0.6 %, 1.0 %, 1.4 %) to evaluate the potential of the composite hydrogel spheres for the application as phycocyanin delivery carriers. The hydrogel spheres' physicochemical properties and bioaccessibility were assessed through scanning electron microscopy, textural analysis, drug-carrying properties evaluation, and in vitro and in vivo controlled release analysis in the gastrointestinal environment. Results indicated that higher sodium alginate concentrations led to smaller pore sizes and denser networks on the surface of hydrogel spheres. The textural properties of hydrogel spheres improved, and their water-holding capacity increased from 93.01 % to 97.97 %. The HP-PC-SA (1.0 %) formulation achieved the highest encapsulation rate and drug loading capacity, at 96.87 % and 6.22 %, respectively. Within the gastrointestinal tract, the composite hydrogel's structure significantly enhanced and protected the phycocyanin's digestibility, achieving a bioaccessibility of up to 88.03 %. In conclusion, our findings offer new insights into improving functionality and the effective use of phycocyanin via pectin-based hydrogel spheres.

PH-responsive supramolecular nanoparticles constructed by Cationic Pillar[5]arenes were used for drug delivery to enhance antitumor activity

ABSTRACT Nano-drug delivery systems have been widely used in antitumor therapy due to their good biocompatibility and low toxicity. However, improving drug-carrying properties and drug release from carriers remains a challenge. In this study, we successfully constructed pH-responsive supramolecular drug-carrying spherical nanoparticles by self-assembling D-alanine-modified water-soluble cationic pillar[5]arene (DAP5) and sodium laurate (SL) to form complexes in aqueous solution. The results demonstrated that DAP5 spherical nanoparticles loaded with doxorubicin hydrochloride (DOX HCl) exhibited an encapsulation rate of 60.0% and a drug loading capacity of 10.5%. These nanoparticles continuously released the drug in a weakly acidic environment that simulates tumour cells. Furthermore, SL⊂DAP5 exhibited good biocompatibility with human normal liver cells (L-02) (IC50 >10 μmol/L), while DOX⊂SL⊂DAP5 demonstrated stronger cytotoxicity against four tumour cells (Hela, HepG2, MGC-803, T-24) compared to free DOX. Notably, DOX⊂SL⊂DAP5 showed an IC50 of only 1.04 μM for HepG2 cells, which was approximately 30.32% of that of DOX (3.43 μM) after 24 hours of incubation. These findings provide valuable insights for the future development of supramolecular drug delivery systems, aiming to enhance drug utilisation and reduce toxic side effects in tumour treatment.

The mechanical properties of lipid nanoparticles depend on the type of biomacromolecule they are loaded with.

For drug delivery systems, the mechanical properties of drug carriers are suspected to play a crucial role in the delivery process. However, there is a lack of reliable methods available to measure the mechanical properties of drug carriers, which hampers the establishment of a link between delivery efficiency and the mechanical properties of carriers. Lipid nanoparticles (LNPs) are advanced systems for delivering nucleic acids to target cell populations for vaccination purposes (mRNA) or the development of new drugs. Hence, it is crucial to develop reliable techniques to measure the mechanical properties of LNPs. In this article, we used AFM to image and probe the mechanical properties of LNPs which are loaded with two different biopolymers either pDNA or mRNA. Imaging the LNPs before and after indentation, as well as recording the retraction curve, enables us to obtain more insight into how the AFM tip penetrates into the particle and to determine whether the deformation of the LNPs is reversible. For pDNA, the indentation by the tip leads to irreversible rupture of the LNPs, while the deformation is reversible for the mRNA-loaded LNPs. Moreover, the forces reached for pDNA are higher than for mRNA. These results pave the way toward the establishment of the link between the LNP formulation and the delivery efficiency.

Elasticity, an often-overseen parameter in the development of nanoscale drug delivery systems.

Nanoparticles have shown an enormous potential as drug delivery systems in the lab. However, translation to the clinics or even market approval often fails. So far, the reason for this discrepancy is manifold. Physicochemical properties such as size, surface potential, and surface chemistry are in focus of research for many years. Other equally important parameters, influencing whether a successful drug delivery can be achieved, are mechanical properties of nanoparticles. Even though this is often not even considered during formulation development, and it is not requested for approval, an increasing number of studies show that it is important to have knowledge about these characteristics. In this article, we discuss examples highlighting the influence of elasticity in nanoscale biological interactions focusing on mucosal delivery and on tumor targeting. Besides this, we discuss the influence of different measurement settings using atomic force microscopy for the determination of mechanical properties of drug carriers.

Quality by Design-Guided Systematic Development and Optimization of Mucoadhesive Buccal Films.

Mucoadhesive buccal films have found increased popularity in pharmaceutical drug delivery due to the several advantages that they possess. The present study strives to develop and optimize chitosan-based mucoadhesive buccal films by relying on quality-by-design (QbD) principles. Previous knowledge and experience were employed to firstly identify the critical quality attributes (CQAs), followed by a thorough risk assessment, which led to the selection of seven critical material attributes and process parameters, namely, the polymer grade and concentration, the plasticizer type and concentration, the citric acid (CA) concentration, the amount of the casted solution, and the drying condition. Their effects on the breaking hardness and mucoadhesivity, selected as CQAs, were investigated in three steps by three designs of the experiment (DoE). The medium molecular weight of chitosan (CH) was the preferred choice in the optimized formulation, and its concentration was the most important factor affecting the CQAs, thickness, and moisture content of the films. It was found that 0.364 g/cm2 was the suitable amount of the casting solution, and its optimum drying conditions were presented in the form of a design space. Glycerol (Gly) was the best choice as a plasticizer, and a design space representing several combinations of CH and CA concentrations that produce films with the required quality was constructed at a fixed concentration of 35% Gly. A formula from this design space was selected and employed to load with two model drugs to test its drug-carrying properties for drugs with different physicochemical characteristics. Uniform drug distribution with an immediate release profile was achieved in both drugs, although one of the CQAs was outside of the specifications in the case of lidocaine-containing film. To summarize, the obtention of the optimum mucoadhesive buccal film based on CH was efficiently facilitated by the rational application of QbD principles and the DoE approach.

Progress of research on graphene and its derivatives in bone and cartilage repair.

In recent years, graphene and its derivatives have gained wide attention in the biomedical field due to their good physicochemical properties, biocompatibility, and bioactivity. Its good antibacterial, osteoinductive and drug-carrying properties make it a promising application in the field of orthopedic biomaterials. This paper introduces the research progress of graphene and its derivatives in bone tissue engineering and cartilage tissue engineering and presents an outlook on the future development of graphene-based materials in orthopedics.

Dual targeting of Mg/N doped-carbon quantum dots with folic and hyaluronic acid for targeted drug delivery and cell imaging

Mg/N doped-carbon quantum dots (CQDs) with dual drug targeting and cell imaging properties was synthesized. Mg/N doped-CQDs synthesized by a hydrothermal method. Operating pyrolysis parameters such as temperature, time, and pH were optimized to achieve CQDs with high quantum yield (QY). This CQD applied in cellular imaging. For the first time, dual active targeting of Mg/N doped CQDs performed using folic acid and hyaluronic acid (CQD-FA-HA). Then, epirubicin (EPI) loaded on this nanocarrier as the final complex (CQD-FA-HA-EPI). Cytotoxicity analysis, cellular uptake, and cell photography performed for the complex on three cell lines, including 4T1, MCF-7, and CHO. In vivo studies were performed in BALB/c inbred female mice models bearing breast cancer. Characterization results showed the successful formation of Mg/N doped-CQDs with a high QY of 89.44%. In vitro drug release approved pH dependency of synthesized nanocarrier with a controlled release behavior. Cytotoxicity tests and cellular uptake results demonstrated increased toxicity and absorption into 4T1 and MCF-7 cell lines for targeted nanoparticles compared to free drug. In cell imaging, an increase in the entry of the complex into 4T1 and MCF-7 cells compared to free drug, confirmed the proper function of the synthesized complex. In vivo results indicated that the tumor volume of mice receiving CQD-FA-HA-EPI was the lowest among other studied groups, along with the lowest damage to the liver, spleen, and heart according to the histopathological analysis. Finally, CQD-FA-HA proposed as a novel platform with tumor targeting, drug carrier, and photoluminescence properties.

Gelothermal Synthesis of Monodisperse MIL-88A Nanoparticles with Tunable Sizes and Metal Centers for Potential Bioapplications.

Developing novel synthetic strategies to downsize metal-organic frameworks (MOFs) from polydisperse crystals to monodisperse nanoparticles is of great importance for their potential bioapplications. In this work, a novel synthetic strategy termed gelothermal synthesis is proposed, in which coordination polymer gel is first prepared and followed by a thermal reaction to give the monodisperse MOF nanoparticles. This novel synthetic strategy successfully leads to the isolation of Materials of Institute Lavoisier (MIL-88), Cu(II)-fumarate MOFs (CufumDMF), and Zeolitic Imidazolate Frameworks (ZIF-8) nanoparticles. Focused on MIL-88A, the studies reveal that the size can be well-tuned from nanoscale to microscale without significant changes in polydispersity index (PDI) even in the case of in situ metal substitution. A possible mechanism is consequently proposed based on extensive studies on the gelothermal condition including sol-gel chemistry, thermal condition, kinds of solvents, and so on. The unique advantages of monodisperse MIL-88A nanoparticles over polydisperse ones are further demonstrated in terms of in vitro magnetic resonance imaging (MRI), cellular uptake, and drug-carrying properties.

Platinum(IV)-Loaded Degraded Glycol Chitosan as Efficient Platinum(IV) Drug Delivery Platform.

A new class of anticancer prodrugs was designed by combining the cytotoxicity of platinum(IV) complexes and the drug carrier properties of glycol chitosan polymers: Unsymmetrically carboxylated platinum(IV) analogues of cisplatin, carboplatin and oxaliplatin, namely (OC-6-44)-acetatodiammine(3-carboxypropanoato)dichloridoplatinum(IV), (OC-6-44)-acetaodiammine(3-carboxypropanoato)(cyclobutane-1,1-dicarboxylato)platinum(IV) and (OC-6-44)-acetato(3-carboxypropanoato)(1R,2R-cyclohexane-1,2-diamine)oxalatoplatinum(IV) were synthesised and conjugated via amide bonding to degraded glycol chitosan (dGC) polymers with different chain lengths (5, 10, 18 kDa). The 15 conjugates were investigated with 1H and 195Pt NMR spectroscopy, and average amounts of platinum(IV) units per dGC polymer molecule with ICP-MS, revealing a range of 1.3-22.8 platinum(IV) units per dGC molecule. Cytotoxicity was tested with MTT assays in the cancer cell lines A549, CH1/PA-1, SW480 (human) and 4T1 (murine). IC50 values in the low micromolar to nanomolar range were obtained, and higher antiproliferative activity (up to 72 times) was detected with dGC-platinum(IV) conjugates in comparison to platinum(IV) counterparts. The highest cytotoxicity (IC50 of 0.036 ± 0.005 µM) was determined in CH1/PA-1 ovarian teratocarcinoma cells with a cisplatin(IV)-dGC conjugate, which is hence 33 times more potent than the corresponding platinum(IV) complex and twice more potent than cisplatin. Biodistribution studies of an oxaliplatin(IV)-dGC conjugate in non-tumour-bearing Balb/C mice showed an increased accumulation in the lung compared to the unloaded oxaliplatin(IV) analogue, arguing for further activity studies.

ROLE OF PARTICLE SIZE, STIFFNESS, AND BLOOD FLOW VELOCITY ON MARGINATION OF NANOSCALE DRUG CARRIERS

Targeted delivery of nanoscale drug carriers is becoming increasingly recognized as an important technology in the treatment of various diseases. The delivery efficiency depends on the ability of the particles drifting in blood flow toward the vascular endothelium and adhering to the specific sites. It is important to identify and understand the key factors that affect this margination process. In this study, the motion and margination of deformable drug carriers, e.g., liposomes in a cell-rich medium, have been investigated with an operator-splitting finite element method. Interactions between particles and fluid are implemented using an immersed boundary approach. We numerically evaluate the effect of particle and flow parameters, such as carrier size, carrier stiffness, and blood flow velocity, on the margination properties of drug carriers. Both the fluid–body interactions and cell–carrier interactions are fully considered. Overall, we observe a waterfall phenomenon which is crucial in the margination for the carriers to reach the cell-free layer (CFL) near the vascular endothelium. Simulation results show that smaller and stiffer carriers display higher tendency of margination and high flow velocity facilitates this process. This investigation provides insights of the margination mechanism, which offer valuable information in predicting the optimum parameters for the design of effective drug delivery systems.

Poly(Glycerol) Microparticles as Drug Delivery Vehicle for Biomedical Use.

Glycerol (Gly) is a well-known, FDA-approved molecule posing three hydroxyl groups. Since Gly is biocompatible, here, it was aimed to prepare poly(Glycerol) (p(Gly)) particles directly for the first time for the delivery of therapeutic agents. Micrometer-sized particles of p(Gly) were successfully synthesized via the micro-emulsion method with an average size of 14.5 ± 5.6 µm. P(Gly) microparticles up to 1.0 g/mL concentrations were found biocompatible with 85 ± 1% cell viability against L929 fibroblasts. Moreover, p(Gly) microparticles were tested for hemocompatibility, and it was found that up to 1.0 mg/mL concentrations the particles were non-hemolytic with 0.4 ± 0.1% hemolysis ratios. In addition, the blood compatibility index values of the prepared p(Gly) particles were found as 95 ± 2%, indicating that these microparticles are both bio- and hemocompatible. Furthermore, Quercetin (QC) flavonoid, which possessed high antioxidant properties, was loaded into p(Gly) microparticles to demonstrate drug-carrying properties of the particles with improved bioavailability, non-toxicity, and high biocompatibility. The results of this study evidently revealed that p(Gly) particles can be directly prepared from a cost-effective and easily accessible glycerol molecule and the prepared particles exhibited good biocompatibility, hemocompatibility, and non-toxicity. Therefore, p(Gly) particles were found as promising vehicles for drug delivery systems in terms of their higher loading and release capability as well as for sustained long term release profiles.

Gelatin methacryloyl/nanosilicate nanocomposite hydrogels encapsulating dexamethasone with a tunable crosslinking density for bone repair

Despite various strategies have been proposed to accelerate bone regeneration, the treatment of bone defects in critical size still remains a clinical challenge. In this study, we fabricated nanocomposite gelatin methacryloyl (GelMA)/nanosilicate (NS) hydrogels for the delivery of dexamethasone (DEX), and systematically investigated their performance in drug delivery for bone repair. Nanocomposite hydrogels were fabricated by mold casting, and exposed to ultraviolet (UV) light to induce covalent crosslinking. Afterwards, we conducted a systematic characterization study to determine the effects of varying NS concentration, GelMA methacrylation degree and UV exposure time on mechanical, structural, and drug release behaviors of nanocomposite hydrogels. In particular, the higher methacrylation degree of GelMA, longer UV exposure and the presence of NS exhibited gradually enhanced mechanical properties. For instance, the compressive strengths of nanocomposite hydrogels containing 0% (w/v) NS (G0NS120) and 3% (w/v) NS (G3NS120) at 120 s of UV exposure were 194.816 kPa–367.284 kPa (p < 0.001), respectively. Similarly, they exhibited higher swelling ratio (%) and slower degradation rate (%) with longer UV exposure and increased NS amount. Nanocomposite hydrogels revealed slower drug release rate due to longer UV exposure and increased NS amount. At day 14 of the release study, 99.53% and 60.687% of DEX were released from G0NS120 and G3NS120, respectively. Particularly, the nanocomposite GelMA/NS hydrogels supported osteoblast adhesion well, and NS and DEX exhibited synergistic effect on osteoblast proliferation with 5.01 fold increase after 7 days of culture. Our results clearly showed that GelMA/NS nanocomposite hydrogels with tunable physiochemical and drug carrier properties could provide a favorable option for accelerating bone repair.

Ciprofloxacin-Loaded Silver Nanoparticles as Potent Nano-Antibiotics against Resistant Pathogenic Bacteria.

Silver nanoparticles (AgNPs) have demonstrated numerous physicochemical, biological, and functional properties suitable for biomedical applications, including antibacterial and drug carrier properties. In the present study, the antibiotic, ciprofloxacin (CIP), was loaded onto AgNPs, which were synthesized via the chemical reduction method, thereby enhancing CIP’s antibacterial activity against Gram-negative (Acinetobacter baumannii and Serratia marcescens) and Gram-positive (Staphylococcus aureus) bacterial strains. Polyethylene glycol–400 (PEG) was used to prepare an AgNPs-PEG conjugate with enhanced stability and to act as the linker between CIP and AgNPs, to produce the novel nanocomposite, AgNPs-PEG-CIP. The prepared AgNPs and their conjugates were characterized by ultraviolet-visible spectrophotometry, Fourier-transform infrared spectroscopy, X-ray diffraction, field emission scanning electron microscopy with energy-dispersive X-ray spectroscopy, transmission electron microscopy, zeta potential analysis, and dynamic light scattering techniques. The inhibitory activity of AgNPs and their conjugates on the growths of pathogenic bacteria was assessed using the well-diffusion method. The results showed the enhanced antibacterial effects of AgNPs-CIP compared to CIP alone. The AgNPs-PEG-CIP nanocomposite showed excellent inhibitory effects against bacterial isolates, with its inhibition zones diameters reaching 39, 36, and 40 mm in S. aureus, A. baumannii, and S. marcescens, respectively. The minimum inhibitory concentration and minimum bactericidal concentration of fogNPs and their conjugates and their antibiofilm effects were also determined. The antioxidant potentials of AgNPs and their conjugates, tested via their 1,1-diphenyl-2-picryl-hydrazyl (DPPH) scavenging ability, showed that the activity increased with increasing AgNPs concentration and the addition of the PEG and/or CIP. Overall, according to the results obtained in the present study, the new nanocomposite, AgNPs-PEG-CIP, showed the highest antibacterial, antibiofilm, and antioxidant activity against the pathogenic bacteria tested, compared to CIP alone. The preparation has high clinical potential for prospective use as an antibacterial agent.

In Vitro Interactions of Amphiphilic Phosphorous Dendrons with Liposomes and Exosomes-Implications for Blood Viscosity Changes.

Drug delivery by dendron-based nanoparticles is widely studied due to their ability to encapsulate or bind different ligands. For medical purposes, it is necessary (even if not sufficient) for these nanostructures to be compatible with blood. We studied the interaction of amphiphilic dendrons with blood samples from healthy volunteers using standard laboratory methods and rheological measurements. We did not observe clinically relevant abnormalities, but we found a concentration-dependent increase in whole blood viscosity, higher in males, presumably due to the formation of aggregates. To characterize the nature of the interactions among blood components and dendrons, we performed experiments on the liposomes and exosomes as models of biological membranes. Based on results obtained using diverse biophysical methods, we conclude that the interactions were of electrostatic nature. Overall, we have confirmed a concentration-dependent effect of dendrons on membrane systems, while the effect of generation was ambiguous. At higher dendron concentrations, the structure of membranes became disturbed, and membranes were prone to forming bigger aggregates, as visualized by SEM. This might have implications for blood flow disturbances when used in vivo. We propose to introduce blood viscosity measurements in early stages of investigation as they can help to optimize drug-like properties of potential drug carriers.

Correction to: Preparation and properties of pH-responsive magnetic mesoporous silica drug carrier

Correction to: Preparation and properties of pH-responsive magnetic mesoporous silica drug carrier

Drug Carriers: A Review on the Most Used Mathematical Models for Drug Release

Carriers are protective transporters of drugs to target cells, facilitating therapy under each points of view, such as fast healing, reducing infective phenomena, and curing illnesses while avoiding side effects. Over the last 60 years, several scientists have studied drug carrier properties, trying to adapt them to the release environment. Drug/Carrier interaction phenomena have been deeply studied, and the release kinetics have been modeled according to the occurring phenomena involved in the system. It is not easy to define models’ advantages and disadvantages, since each of them may fit in a specific situation, considering material interactions, diffusion and erosion phenomena, and, no less important, the behavior of receiving medium. This work represents a critical review on main mathematical models concerning their dependency on physical, chemical, empirical, or semi-empirical variables. A quantitative representation of release profiles has been shown for the most representative models. A final critical comment on the applicability of these models has been presented at the end. A mathematical approach to this topic may help students and researchers approach the wide panorama of models that exist in literature and have been optimized over time. This models list could be of practical inspiration for the development of researchers’ own new models or for the application of proper modifications, with the introduction of new variable dependency.

Preparation and properties of pH-responsive magnetic mesoporous silica drug carrier

Preparation and properties of pH-responsive magnetic mesoporous silica drug carrier

Cross-linking polymerization of beta-cyclodextrin with acrylic monomers; characterization and study of drug carrier properties

Cross-linking polymerization of beta-cyclodextrin with acrylic monomers; characterization and study of drug carrier properties

Cyclodextrin-based low melting mixtures as a solubilizing vehicle: Application to non-steroidal anti-inflammatory drugs

Poor water solubility represents a serious issue for drug formulation and delivery. Cyclodextrins (CDs) and cosolvents are valuable approaches to overcome this issue. Currently, there is a growing interest in deep eutectic solvents (DESs) with high solubilizing ability and low toxicity. Low melting mixtures (LMMs) based on CDs have recently emerged, combining the solubilizing properties of solvents and drug carriers. In this study, we evaluated the solubility of ketoprofen, flurbiprofen and naproxen in two mixtures based on levulinic acid (Lev). The effect of water on the solubilizing potential and viscosity of these mixtures was assessed. Also, the stability of the studied drugs was monitored up to one year. The LMM based on randomly methylated-β-cyclodextrin (RAMEB) showed the highest solubilizing potential (up to 5012-fold the aqueous solubility) compared to the DES based on choline chloride. Formation of RAMEB/drug inclusion complex in the LMM was evidenced by nuclear magnetic resonance spectroscopy (NMR). Adding water (10 wt%) sharply reduced the viscosity of both mixtures while maintaining their high solubilizing ability. Moreover, the studied drugs were stable up to 90% in both mixtures after a year at 25 °C. Such low-viscous mixtures endowed with high solubilizing and stabilizing properties have great potential for pharmaceutical applications.

In situ preparation of hydroxyapatite in lamellar liquid crystals for joint lubrication and drug delivery.

Arthritis is a disease that seriously affects the quality of human life, which is partly caused by the reduction of joint lubrication performance. Thus, for the treatment of arthritis, how to improve the lubrication performance of joints is important. The lamellar liquid crystals (LLCs) systems have the potential to be used as joint lubrication due to their double-layer structure and good biocompatibility, however, the LLCs system alone could not provide a satisfactory lubrication effect. Herein, this work synthesized hydroxyapatite (HAP) in situ inside Tween 85/Tween 80/H2O LLCs to construct a biocompatible HAP/Tween 85/Tween 80/H2O LLCs (HAP/LLCs) lubrication system with both sustained drug release properties and anti-wear properties. HAP is the main component of bone with good stability and bioactivity. The LLCs have good lubricating and drug-carrying properties. The impact of HAP on the structure and lubrication properties of LLCs, the mechanism of friction, and the anti-wear reduction of HAP/LLCs were investigated. Moreover, the drug release behavior of the ibuprofen-loaded HAP/LLCs during the friction process was also studied. The results indicated that the addition of HAP could improve the lubricity performance of LLCs. The cumulative drug releasing increased with the friction frequency and was less affected by the load. The related studies provided the theoretical basis for HAP/LLCs for joint lubrication and synergistic therapy.