Potential Drug Delivery System Research Articles

A PLLA Coating Does Not Affect the Insertion Pressure or Frictional Behavior of a CI Electrode Array at Higher Insertion Speeds.

To prevent endocochlear insertion trauma, the development of drug delivery coatings in the field of CI electrodes has become an increasing focus of research. However, so far, the effect of a polymer coating of PLLA on the mechanical properties, such as the insertion pressure and friction of an electrode array, has not been investigated. In this study, the insertion pressure of a PLLA-coated, 31.5-mm long standard electrode array was examined during placement in a linear cochlear model. Additionally, the friction coefficients between a PLLA-coated electrode array and a tissue simulating the endocochlear lining were acquired. All data were obtained at different insertion speeds (0.1, 0.5, 1.0, 1.5, and 2.0 mm/s) and compared with those of an uncoated electrode array. It was shown that both the maximum insertion pressure generated in the linear model and the friction coefficient of the PLLA-coated electrode did not depend on the insertion speed. At higher insertion speeds above 1.0 mm/s, the insertion pressure (1.268 ± 0.032 mmHg) and the friction coefficient (0.40 ± 0.15) of the coated electrode array were similar to those of an uncoated array (1.252 ± 0.034 mmHg and 0.36 ± 0.15). The present study reveals that a PLLA coating on cochlear electrode arrays has a negligible effect on the electrode array insertion pressure and the friction when higher insertion speeds are used compared with an uncoated electrode array. Therefore, PLLA is a suitable material to be used as a coating for CI electrode arrays and can be considered for a potential drug delivery system.

Chitosan-functionalized Fe3O4@SiO2 nanoparticles as a potential drug delivery system

Chitosan-functionalized Fe3O4@SiO2 nanoparticles as a potential drug delivery system

Second-Order Scattering Quenching in Fluorescence Spectra of Natural Humates as a Tracer of Formation Stable Supramolecular System for the Delivery of Poorly Soluble Antiviral Drugs on the Example of Mangiferin and Favipiravir.

In the present work, the methods of dynamic light scattering and fluorescence spectroscopy were applied to study the optical properties of aqueous dilutions of the humic substances complex (HC) as a potential drug delivery system. The supramolecular structures in the humate solution were characterized as monodisperse systems of the submicron range with a tendency to decrease in particle size with a decrease in the dry matter concentration. The slightly alkaline medium (8.3) of the studied aqueous dilutions of HC causes the absence of a pronounced fluorescence maximum in the region from 400 to 500 nm. However, the presence of an analytically significant, inversely proportional to the concentration second-order scattering (SOS) signal at 2λex = λem was shown. In the examples of the antiviral substances mangiferin and favipiravir, it was shown that the use of the humic complex as a drug carrier makes it possible to increase the solubility by several times and simultaneously obtain a system with a smaller particle size of the dispersed phase. It has been shown that HC can interact with mangiferin and favipiravir to form stable structures, which lead to a significant decrease in SOS intensities on HC SOS spectra. The scattering wavelengths, λex/λem, were registered at 350 nm/750 nm for mangiferin and 365 nm/730 nm for favipiravir, respectively. The increments of the scattering intensities (I0/I) turned out to be proportional to the concentration of antiviral components in a certain range of concentrations.

Optimization of the Conditions of Solid Lipid Nanoparticles (SLN) Synthesis.

Solid lipid nanoparticles (SLNs) have been synthesized as potential drug delivery systems. They are classified as solid lipid nanocarriers that can successfully carry both hydrophilic and hydrophobic drugs. SLNs are based on a biocompatible lipid matrix that is enzymatically degraded into natural components found in the human body. Solid lipid nanoparticles are suitable for the incorporation of hydrophobic active ingredients such as curcumin. The study included the optimization of lipid nanoparticle composition, incorporation of the active compound (curcumin), a stability evaluation of the obtained nanocarriers and characterization of their lipid matrix. Through process optimization, a dispersion of solid lipid nanoparticles (solid lipid:surfactant—2:1.25 weight ratio) predisposed to the incorporation of curcumin was developed. The encapsulation efficiency of the active ingredient was determined to be 99.80%. In stability studies, it was found that the most suitable conditions for conducting high-pressure homogenization are 300 bar pressure, three cycles and a closed-loop system. This yields the required values of the physicochemical parameters (a particle size within a 200–450 nm range; a polydispersity index of <30%; and a zeta potential of about |±30 mV|). In this work, closed-loop high-pressure homogenization was used for the first time and compared to the currently preferred open-loop method.

Hydrophilic drug release from electrospun membranes made out of thermo and pH-sensitive polymers

Electrospun fibers of the thermo-and pH sensitive poly(N-vinylcaprolactam-co-acrylic acid) (Poly(NVCL-co-AA) loaded with 10% and 30 wt% caffeine (Caf) were obtained by electrospinning and evaluated as potential drug delivery systems. Caffeine was used as a hydrophilic drug model, and poly(NVCL-co-AA) containing either 20 or 30 mol% AA was used as a carrier. The fibers morphology, as well as, their interaction with caffeine, were studied using different analytical techniques. The cytotoxicity of the different obtained fibers was evaluated by cell viability assays using 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and mouse embryonic fibroblasts cell line (MEF cells). Caffeine release was studied at temperatures of 25 °C and 42 °C and pH of 1.2 and 7.4. Beadless copolymer fibers with diameters ranging from 1 μm to 2 μm were obtained. The addition of caffeine, which was in crystalline form after being encapsulated in the fibers, resulted in an increase of fiber diameter. The obtained membranes were found to be not cytotoxic. The entrapment of caffeine was greater for the copolymer containing 30 mol% AA due to a greater affinity of AA to caffeine. At a pH of 1.2 and at both temperatures of 25 °C and 42 °C, as well as, at a pH of 7.4 and a temperature of 42 °C, a Fickian diffusion mechanism for all copolymer fiber mats was observed. At a pH of 7.4 and 25 °C the release profile showed a high rate and followed a zero-order model, due to the fast dissolution of caffeine in water. These results indicated that thermo-and pH-sensitive poly(NVCL-co-AA) are promising candidates for controlled release of hydrophilic drugs.

Smart Injectable Chitosan Hydrogels Loaded with 5-Fluorouracil for the Treatment of Breast Cancer.

The treatment of breast cancer requires long chemotherapy management, which is accompanied by severe side effects. Localized delivery of anticancer drugs helps to increase the drug concentration at the site of action and overcome such a problem. In the present study, chitosan hydrogel was prepared for local delivery of 5-Fluorouracil. The in vitro release behavior was investigated and the anticancer activity was evaluated against MCF-7 cells using MTT assay. The in vivo studies were investigated via intra-tumoral injection of a 5-FU loaded hydrogel into breast cancer of female rats. The results indicated that the modified hydrogel has excellent physicochemical properties with a sustained in vitro release profile matching a zero-order kinetic for one month. In addition, the hydrogel showed superior inhibition of cell viability compared with the untreated control group. Moreover, the in vivo studies resulted in antitumor activity with minor side effects. The tumor volume and level of tumor markers in blood were inhibited significantly by applying the hydrogel compared with the untreated control group. In conclusion, the designed injectable hydrogels are potential drug delivery systems for the treatment of breast cancer with a controlled drug release profile, which could be suitable for decreasing the side effects of chemotherapy agents.

Impact of Fluorinated Ionic Liquids on Human Phenylalanine Hydroxylase-A Potential Drug Delivery System.

Phenylketonuria (PKU) is an autosomal recessive disease caused by deficient activity of human phenylalanine hydroxylase (hPAH), which can lead to neurologic impairments in untreated patients. Although some therapies are already available for PKU, these are not without drawbacks. Enzyme-replacement therapy through the delivery of functional hPAH could be a promising strategy. In this work, biophysical methods were used to evaluate the potential of [N1112(OH)][C4F9SO3], a biocompatible fluorinated ionic liquid (FIL), as a delivery system of hPAH. The results herein presented show that [N1112(OH)][C4F9SO3] spontaneously forms micelles in a solution that can encapsulate hPAH. This FIL has no significant effect on the secondary structure of hPAH and is able to increase its enzymatic activity, despite the negative impact on protein thermostability. The influence of [N1112(OH)][C4F9SO3] on the complex oligomerization equilibrium of hPAH was also assessed.

Guar gum-g-poly(N-acryloyl-L-phenyl alanine) based pH responsive smart hydrogels for in-vitro anticancer drug delivery

ABSTRACT In this study, modified natural polymeric-based pH-responsive hydrogels (GNAHs) were formulated using guar gum-grafted-poly(N-acryloyl phenyl alanine), 2-hydroxy ethyl acrylate, and 2-acrylamido-2-methyl-1-propane sulfonic acid. GNAH hydrogels were synthesized using a single-step radical polymerization reaction using N,N’-methylenebisacrylamide as a crosslinker and potassium persulfate as an initiator. The GNAH was used for the controlled release of Imatinib mesylate (IMS), an anticancer drug. The FTIR spectroscopy confirmed the IMS loading as well as grafting reaction between GG-g-PNPA and PHEA-co-PAMPS. This was further confirmed by XRD and DSC studies. The IMS also reduced the negative surface charge of the GNAH hydrogel. The microscopic images showed that the GNAH hydrogels have porous and canal structures with IMS molecules entrapped within the pores. The mode of drug release mechanism was assessed by applying various kinetic equations (non-Fickian diffusion mechanism, Higuchi square root and Korsmeyer–Peppas kinetic models) that showed pH-dependent drug release of hydrogels exhibiting an excellent controlled-release pattern for IMS for more than 48 h. Based on the drug release behavior of the as-synthesized amino acid-functionalized hydrogel, it can be suggested that GNAH hydrogels could also be used as a potential pH-responsive anticancer drug delivery system for other anticancer drugs.

Bandage contact lens soaked in 0.1% diclofenac to relieve early postoperative pain and foreign body sensation after transepithelial photorefractive keratectomy.

To study the effects of a bandage contact lens immersed in 0.1% diclofenac on pain management for patients undergoing transepithelial photorefractive keratectomy (TPRK). In a prospective, comparative, contralateral, randomized, double-masked study, we assessed a total of 51 patients. The eyes of each patient were randomly divided into two groups. After TPRK, a normal soft bandage contact lens was placed on one eye as the control group, and a bandage contact lens soaked in diclofenac was placed on the other eye as the experimental group. When the bandage contact lens was not removed, postoperative pain and other ocular discomforts were compared at 2, 18, and 24 h and 2, 3, 4, and 5 postoperative days. Patients were then examined after 1 month. Visual acuity and subepithelial haze were also evaluated. The mean pain score was 2.69 ± 1.96 in the control group, which was significantly higher than that in the experimental group, which received the diclofenac-soaked bandage contact lens at 2 postoperative hours. The statistical difference between the two groups' mean foreign body sensation at 2 postoperative hours was detected (p = 0.035). No differences were detected between the two groups' subepithelial haze scores or visual acuity. A bandage contact lens soaked in 0.1% diclofenac solution can be used as a potential drug-delivery system to relieve early postoperative pain and foreign body sensation after TPRK.

Limited Impact of the Protein Corona on the Cellular Uptake of PEGylated Zein Micelles by Melanoma Cancer Cells.

The formation of a protein layer “corona” on the nanoparticle surface upon entry into a biological environment was shown to strongly influence the interactions with cells, especially affecting the uptake of nanomedicines. In this work, we present the impact of the protein corona on the uptake of PEGylated zein micelles by cancer cells, macrophages, and dendritic cells. Zein was successfully conjugated with poly(ethylene glycol) (PEG) of varying chain lengths (5K and 10K) and assembled into micelles. Our results demonstrate that PEGylation conferred stealth effects to the zein micelles. The presence of human plasma did not impact the uptake levels of the micelles by melanoma cancer cells, regardless of the PEG chain length used. In contrast, it decreased the uptake by macrophages and dendritic cells. These results therefore make PEGylated zein micelles promising as potential drug delivery systems for cancer therapy.

Crosslinked nanocollagen-cellulose nanofibrils reinforced electrospun polyvinyl alcohol/methylcellulose/polyethylene glycol bionanocomposites: Study of material properties and sustained release of ketorolac tromethamine

Engaged potent drug delivery systems (DDSs) has greatly influence on managing the drug pharmacological outcome and the pharmacokinetic outline with regards to the drug release rate, the target site, drug bioavailability without neglecting the side effects. The endeavor of this work is to investigate the effect of reinforcing nanofillers on drug release, and other properties of the nanofiller-drug loaded nanofibrous systems. In this research work, cellulose nanofibrils (CNF) has been isolated from jute fibres while nanocollagen (NCG) was extracted from waste fish scales for the fabrication of CNF-NCG reinforced drug loaded PVA/MC/PEG glutaraldehyde cross-linked novel electrospun nanofibrous bionanocomposites (BNCs). The prepared BNCs were characterized by Fourier Transform Infrared (FTIR) Spectroscopy and Field emission scanning electron microscopy (FESEM). In vitro drug release results showed that the CNF-NCG BNCs loaded nanofibrous structures displayed excellent sustained release of KT up to ≥16 h and can serve as excellent transdermal DDSs.

Lactoferrin-loaded nanostructured lipid carriers (NLCs) as a new formulation for optimized ocular drug delivery

Nanostructured lipid carriers (NLC) are novel lipidic nanosystems that provide significant improvements in terms of high drug loading capacity and controlled drug release. The purpose of the present work was based on the design, development, and physicochemical characterization of lactoferrin-loaded NLCs as a new therapeutic alternative for the keratoconus treatment. Lactoferrin-loaded NLCs were successfully prepared by a double emulsion/solvent evaporation method. The resultant NLC were assessed in terms of particle size, size distribution, surface charge, morphology, encapsulation efficiency (EE), loading capacity (LC), stability, cytotoxicity, in vitro release, and ocular surface retention. Resulting data showed a size of 119.45 ± 11.44 nm, a 0.151 ± 0.045 PDI value and a surface charge of −17.50 ± 2.53 mV. Besides, high EE and LC values were obtained (up to 75%). The in vitro release study demonstrated a lactoferrin controlled release pattern. NLCs were also stable, non-toxic and show mucoadhesive properties. Thus, a consistent preclinical base was obtained, where NLC may be considered as a potential controlled release novel drug delivery system of lactoferrin for the keratoconus treatment.

The Apoptosis of Liver Cancer Cells Promoted by Curcumin/TPP-CZL Nanomicelles With Mitochondrial Targeting Function.

The mitochondrion is one of the most important cellular organelles, and many drugs work by acting on mitochondria. Curcumin (Cur)-induced apoptosis of HepG2 in liver cancer cells is closely related to the function of inhibiting mitochondria. However, the mitochondrion-targeting curcumin delivery system was rarely been reported. It is important to develop a high-efficiency mitochondrion-targeting curcumin vector that can deliver curcumin into mitochondria directly. Here, a special mitochondrion-targeting delivery system based on triphenylphosphine bromide (TPP)-chitosan-g-poly-(N-3-carbobenzyloxy-l-lysine) (CZL) with TPP functional on the surface is designed to perform highly efficient mitochondria-targeting delivery for effective liver cancer cell killing in vitro. The TEM images showed that the nanomicelles were spherical; the results of fluorescence test showed that TPP-CZL nanomicelles could promote the cellular uptake of drugs and finally targeted to the mitochondria. The results of cell survival rate and Hoechst staining showed that curcumin/TPP-CZL nanomicelles could promote the apoptosis of liver cancer cells. Curcumin/TPP-CZL nanomicelles could significantly reduce the mitochondrial membrane potential, increase the expression of pro apoptotic protein Bcl-2, and reduce the expression of antiapoptotic Bax protein, and these results were significantly better than curcumin/CZL nanomicelles and curcumin. It is a potential drug delivery system with high efficiency to target mitochondria of liver cancer cells.

Plasma Bead Entrapped Liposomes as a Potential Drug Delivery System to Combat Fungal Infections.

Fibrin-based systems offer promises in drug and gene delivery as well as tissue engineering. We established earlier a fibrin-based plasma beads (PB) system as an efficient carrier of drugs and antigens. In the present work, attempts were made to further improve its therapeutic efficacy exploiting innovative ideas, including the use of plasma alginate composite matrices, proteolytic inhibitors, cross linkers, and dual entrapment in various liposomal formulations. In vitro efficacy of the different formulations was examined. Pharmacokinetics of the formulations encapsulating Amphotericin B (AmpB), an antifungal compound, were investigated in Swiss albino mice. While administration of the free AmpB led to its rapid elimination (<72 h), PB/liposome-PB systems were significantly effective in sustaining AmpB release in the circulation (>144 h) and its gradual accumulation in the vital organs, also compared to the liposomal formulations alone. Interestingly, the slow release of AmpB from PB was unusual compared to other small molecules in our earlier findings, suggesting strong interaction with plasma proteins. Molecular interaction studies of bovine serum albumin constituting approximately 60% of plasma with AmpB using isothermal titration calorimetry and in silico docking verify these interactions, explaining the slow release of AmpB entrapped in PB alone. The above findings suggest that PB/liposome-PB could be used as safe and effective delivery systems to combat fungal infections in humans.

Novel poly(sulfobetaine methacrylate) based carriers as potential ocular drug delivery systems for timolol maleate

AbstractPolyzwitterions are biocompatible and protein‐adsorption‐resistant polymers which makes them very attractive for pharmaceutical applications, especially as drug and gene delivery systems. Two different poly(sulfobetaine methacrylate) (PSB) based vehicles were synthesised in the present study using reversible addition‐fragmentation chain transfer polymerization, namely linear macromolecules and a crosslinked network as microgels, in order to be tested as ocular drug delivery systems for timolol maleate (TM). The differences in their structure were expected to result in different physicochemical properties as well as in different performances as potential ocular drug delivery systems. The PSB vehicles' structure and properties were investigated using dynamic light scattering, zeta potential measurements and SEM. The drug entrapment efficiency of TM in both PSB carriers was determined and the TM release profiles were monitored. In this way, the relationship between the PSB vehicles' structure and the TM release profiles was outlined. © 2022 Society of Industrial Chemistry.

Large Azobenzene Macrocycles: Formation and Detection by NMR and MS Methods

ABSTRACT Azobenzene macrocycles are widely investigated as potential drug delivery systems and as part of molecular machines due to their photo-responsive properties. Herein, we detect the formation of a series of new azobenzene macrocycles that feature up to eight switchable repeating units. High-resolution mass spectrometry and ion mobility (IM) mass spectrometry experiments and 1H and diffusion-ordered spectroscopy (DOSY) NMR are used to detect the presence of the macrocycles that contain 10 to 40 aromatic rings in the gas phase and solution, respectively. The responsiveness of the Z-to-E photo-switching of the smallest of the macrocycles, exhibiting two azobenzene units and in total 10 aromatic rings, separated with column chromatography, is studied with irradiation experiments, using both UV-Vis light and thermal excitation and relaxation, and monitoring the sample with UV-Vis absorption and 1H NMR spectroscopy. DFT calculations are used to understand the conformation of this isolated species in solution.

Stereolithography 3D printed implants: A preliminary investigation as potential local drug delivery systems to the ear

The current study is a preliminary investigation on the use of stereolithography 3D printing technology in the field of personalized medicines and specifically for delivering drugs locally, which can for example usefully be applied to ear infections. The main aim is the development of drug-loaded implants for the treatment of ear diseases, to improve patient compliance and to overcome the limitations of current delivery approaches. Multiple prototypes of implant geometries have been created and printed using a flexible resin containing 0.5% w/v of Levofloxacin. Physicochemical characterization of the printed implants was carried out using a variety of techniques (e.g., microscopic, spectroscopic, and mechanical analysis). Finally, preliminary in vitro tests were performed to evaluate the release profile of Levofloxacin, the prototype implant's stability, and their antimicrobial property. The results obtained show that there is no interaction between the resin and the drug, which is perfectly solubilized in the device. In addition, the results of the mechanical tests show that the material used resists compression without compromising the design itself, and the diffusion test has shown that the drug diffused through the matrix prototype at 50% over 3 weeks. The selected designs showed higher antimicrobial activity on E. coli than on S. aureus.

Permeation enhancer nanovesicles mediated topical delivery of curcumin for the treatment of hyperpigmentation

The main aim of the present study was to develop curcumin (CUR) loaded permeation enhancer-lipid vesicles for the treatment of hyperpigmentation. Hyperpigmentation is an acquired skin disorder characterized by uneven skin coloration, mainly in the regions of the facial skin, affecting millions of people worldwide. It often occurs in visible areas, hence causing significant negative psychological and social impacts. In the present study, curcumin-loaded permeation enhancer nanovesicles (PE-NVs) were developed by modified ethanol injection method and dimethyl sulfoxide was added as a penetration enhancer. PE-NVs were subjected to various physicochemical characterizations and drug permeation studies across the skin. The PE-NVs were tested for their efficacy in a sunlight-induced hyperpigmented rabbit skin model. Topical application of PE-NVs reduced symptoms of hyperpigmentation as compared with CUR methanolic solution because of higher accumulation because of better permeation into skin layers. Histopathological studies also confirmed the effectiveness of PE-NVs, since they reduced hyperpigmentation-induced lesions. Results confirmed that PE-NVs is a potential drug delivery system for topical administration drugs to treat skin-associated inflammatory disorders.

Preparation and pharmacodynamics of niclosamide micelles

Niclosamide (NIC) has been found to have outstanding antitumour activity in recent years, but its clinical application has been limited by its poor water solubility. In this study, nanomicelles (PEG2K-Fmoc-Ibuprofen micelles, PEG2K-FIbu) were prepared as carriers to improve the solubility and bioavailability of NIC. Nuclear magnetic resonance (NMR) confirmed its successful preparation. The drug-carrying micelles (PEG2K-FIbu/NIC) were then prepared using a thin film dispersion method. PEG2K-FIbu and PEG2K-FIbu/NIC were analysed in detail in terms of particle size, polymer dispersion index, stability and encapsulation efficiency. Finally, the in vivo effects of PEG2K-FIbu/NIC were tested in a mouse liver cancer model. The particle size of PEG2K-FIbu was 11.11 nm. The encapsulation rate was 70.4% and the tumour inhibition rate was 55.98%. Tumours were significantly reduced and damage to the liver was greatly reduced. The histopathological sections and serum biochemical indices also showed that the symptoms were significantly improved after administration. In summary, PEG2K-FIbu/NIC is a potential drug delivery system of NIC to effectively treat liver cancer, providing an effective dosage form for NIC.

Silica Nanoparticles Promote α-Synuclein Aggregation and Parkinson's Disease Pathology.

Silica nanoparticles (SiO2 NPs) are increasingly investigated for their potential in drug delivery systems. However, the neurotoxicity of SiO2 NPs remains to be fully clarified. Previously SiO2 NPs have been reported to be detected in the central nervous system, especially in the dopaminergic neurons which are deeply involved in Parkinson’s disease (PD). In this article, we characterized the effects of SiO2 NPs on inducing PD-like pathology both in vitro and in vivo. Results showed that SiO2 NPs promote more severe hyperphosphorylation and aggregation of α-synuclein, mitochondria impairment, oxidative stress, autophagy dysfunction, and neuronal apoptosis in the α-Syn A53T transgenic mice intranasally administrated with SiO2 NPs compared with the control group. Our findings provide new evidence supporting that SiO2 NPs exposure might have a strong capability of promoting the initiation and development of PD.