A significant antibiofilm and antimicrobial activity of chitosan-polyacrylic acid nanoparticles against pathogenic bacteria.

Chitosan is known to exert antimicrobial activity without the need for any chemical modification; however, new derivatives of chitosan can be created to target multi-drug resistant bacteria. In this study, chitosan (CS) was cross-linked with sodium tripolyphosphate to form nanoparticles, which were then coated with polyacrylic acid (PAA). The SEM images revealed that the CS-PAA nanoparticles had spherical shapes with smooth surfaces and the size of the dried nanoparticles was approximately 222 nm. Biofilm formation was significantly inhibited by 0.5 mg/mL of CS-PAA. In-situ optical microscopy showed that CS-PAA nanoparticles inhibited the bacterial biofilm formation in Campylobacter jejuni, Pseudomonas aeruginosa, and Escherichia coli after a single treatment with 40 µg. Additionally, 20 µg of CS-PAA nanoparticles demonstrated antibacterial activity against the growth of C. jejuni, P. aeruginosa, and E. coli with notable inhibitory zones of 9, 12, and 13 mm, respectively (P < 0.01). The development of a novel and ecofriendly method for the preparation of chitosan nanoparticles through an interaction of chitosan with PAA shows promise tool to combat bacterial infections and validates effective antibacterial and antibiofilm properties against antibiotic resistant pathogens.

Perspective of biopharmaceutics knowledge and practice of pharmacy personnel toward the effect of medication route and medical procedure on nullifying fasting.

Background: In Ramadan, most of the dosing schedules for the patients are changed, and to ensure patient compliance to medications and to healthy life among patients, appropriate guidelines and educations are needed. This can be achieved by pharmacy personnel in all clinical settings who are recognized as biopharmaceutical experts and integral educators of medications. Aims: This study aimed to identify the perspective knowledge of pharmacy personnel about effect of medication route and medical procedure on nullifying fasting in Ramadan and to determine the predictors of this knowledge. Methods: A cross-sectional study was conducted in Jordan during March-April 2022. An internet-based self-administrated questionnaire on knowledge, and views was distributed using social media groups to the pharmacy personnel among different geographical areas in Jordan. A descriptive and univariate analysis were performed. Binary logistic regression was conducted to determine the predictors of knowledge including all variables with p < 0.20 on univariate analysis. Results: A total of 1003 responses to the study questionnaire were collected and included in the analysis. The most common source that pharmacy personnel used to get information on medication intake and medical procedures during fasting in Ramadan was Fatwa (57.8%) followed by Islamic materials "books and brochures" (47.1%). The majority of respondents were knowledgeable about the effect of administration route of medication and medical procedures on nullifying fasting in Ramadan (greater than70%). The univariate analysis showed that more than half of respondents (56.1%) were considered knowledgeable, and the binary logistic regression analysis identified that both professional degree type and confidence of respondents to modify the patient's medication schedule as predictors for knowledge (OR = 1.791, 95% CI = 1.035-3.098, p = 0.037), (OR = 1.375, 95% CI = 1.04-1.817, p = 0.025), respectively. Conclusions: Most of pharmacy personnel in Jordan are knowledgeable in biopharmaceutics principles and practice toward effect of medication route and medical procedure on nullifying fasting, and the identified predictors for this knowledge, can provide an opportunity to improve safe and effective use of medications and medical procedures during the holy month of Ramadan.

In vivo tests of a novel wound dressing based on agar aerogel.

Aerogels, especially bio-based ones, present a promising option for wound dressing; specifically, because of their low toxicity, high stability, bio-compatibility, and good biological performance. In this study, agar aerogel was prepared and evaluated as novel wound dressing material in an in vivo rat study. Agar hydrogel was prepared by thermal gelation, after that the water inside the gel was exchanged with ethanol, and finally the alcogel was dried by supercritical CO2. The textural and rheological properties of the prepared aerogel were characterized, showing that the prepared agar aerogels possess high porosity (97-98 %), high surface area (250-330 m2g-1) as well as good mechanical properties and easiness of removal from the wound site. The results of the in vivo experiments macroscopically demonstrate the tissue compatibility of the aerogels in dorsal interscapular injured rat tissue and a shorter wound healing time comparable to that of gauze-treated animals. The histological analysis underpins the reorganisation and healing of the tissue for the injured skin of rats treated with agar aerogel wound dressing within the studied time frame.

Comparison of Nozzle-Based and Nozzle-Free Electrospinning for Preparation of Fast-Dissolving Nanofibers Loaded with Ciprofloxacin.

The study aimed to prepare ciprofloxacin-loaded polyvinylpyrrolidone electrospun nanofibers for oral drug delivery, using a conventional nozzle-based and a lab-built nozzle-free electrospinning equipment. To produce nanofibers, electrospinning is the process most often used. However, from the industry's point of view, conventional electrospinning does not have sufficiently high productivity. By omitting the nozzle, productivity can be increased, and so the development of nozzle-free processes is worthwhile. In this study, a solution of ciprofloxacin and polyvinylpyrrolidone was electrospun under similar conditions, using both single-nozzle and nozzle-free methods. The two electrospinning methods were compared by investigating the morphological and physicochemical properties, homogeneity, in vitro drug release, and cytotoxicity. The stability of the nanofibers was monitored from different aspects in a 26 month stability study. The results showed that the use of the nozzle-free electrospinning was preferable due to a higher throughput, improved homogeneity, and the enhanced stability of nanofiber mats, compared to the nozzle-based method. Nevertheless, fast dissolving nanofibers loaded with poorly water-soluble ciprofloxacin were produced by both electrospinning methods. The beneficial properties of these nanofibers can be exploited in innovative drug development; e.g., nanofibers can be formulated into orodispersible films or per os tablets.

Smartcrystals for Efficient Dissolution of Poorly Water-Soluble Meloxicam.

Nanocrystal is widely applied to improve the dissolution of poorly water-soluble drugs. We aimed to prepare meloxicam (MLX) nanocrystals using the bead mill method, followed by high-pressure homogenization (HPH). Simple drying at room temperature (RD), vacuum-drying (VD), and freeze-drying (FD) using mannitol or trehalose as a cryoprotectant were applied to obtain dry nanocrystals. The nanocrystals were fully characterized. The MLX nanosuspension containing 5% w/v MLX and 1% w/v of Pluronic F68 showing a mean particle size (MPS) of 242 nm and a polydispersity index (PDI) of 0.36 was prepared after 40 min of premilling and 30 min of HPH. The dried nanocrystals were spherical within the nano range. DSC and XRPD confirmed the absence of MLX amorphization. The smartcrystals showed enhanced MLX release. Approximately 100% release was achieved with phosphate buffer (PB), pH 5.6, and 80% was released with PB, pH 7.4, from the freeze-dried samples. The results revealed the effects of the drying method and cryoprotectant type on the properties of dry nanocrystals. The freeze-dried samples showed the smallest particle size, in particular trehalose-based samples. On the other hand, mannitol-based dried samples showed the highest crystallinity index among all nanocrystals (77.8%), whereas trehalose showed the lowest (59.2%). These factors explained the dissolution differences among the samples.

Nasal delivery of nanosuspension-based mucoadhesive formulation with improved bioavailability of loratadine: Preparation, characterization, and in vivo evaluation.

The unique requirements of poorly water-soluble drug delivery have driven a great deal of research into new formulations and routes of administration. This study investigates the use of nanosuspensions for solubility enhancement and drug delivery. Simple methods were used to prepare nasal formulations of loratadine based on nanosuspension pre-dispersion with sodium hyaluronate as a mucoadhesive agent. The nanosuspension was prepared by antisolvent precipitation method followed by ultrasonication and characterized for particle size, polydispersity index, zeta potential, morphology, and structure. Moreover, the nasal formulations were characterized for drug loading, pH, particle size, viscosity, bioadhesive viscosity parameter, and were evaluated for in vitro dissolution and diffusion, in addition to in vivo studies in a rat model. Loratadine nanosuspension displayed a particle size of 311 nm, a polydispersity index of 0.16, and zeta potential of -22.05 mV. The nanosuspension preserved the crystalline status of the raw drug. The addition of sodium hyaluronate exhibited an increase in the mean particle size and zeta potential of the nanoparticles. The nasal formulations showed enhanced bioadhesive properties compared to the unprocessed loratadine in the reference samples. The nanosuspension based-formulation that contained 5 mg mL-1 sodium hyaluronate and 2.5 mg mL-1 loratadine (NF4) showed a significant enhancement of flux and permeability coefficient through a synthetic membrane. NF4 exhibited 24.73 µg cm-2 h-1 and 0.082 cm h-1, while the reference sample showed 1.49 µg cm-2 h-1 and 0.017 cm h-1, for the flux and the permeability coefficient, respectively. Nasal administration of NF4 showed a bioavailability of 5.54-fold relative to the oral administration. The results obtained in this study indicate the potential of the nasal route and the nanosuspension for loratadine delivery. The relative bioavailability of NF4 was 1.84-fold compared to unprocessed loratadine in the reference sample. Therefore, the nanosized loratadine could be suggested as a practical and simple nanosystem for the intranasal delivery with improved bioavailability.

Intranasal Nanoparticulate Systems as Alternative Route of Drug Delivery.

There is always a need for alternative and efficient methods of drug delivery. The nasal cavity can be considered as a non-invasive and efficient route of administration. It has been used for local, systemic, brain targeting, and vaccination delivery. Although many intranasal products are currently available on the market, the majority is used for local delivery with fewer products available for the other targets. As nanotechnology utilization in drug delivery has rapidly spread out, the nasal delivery has become attractive as a promising approach. Nanoparticulate systems facilitate drug transportation across the mucosal barrier, protect the drug from nasal enzyme degradation, enhance the delivery of vaccines to the lymphoid tissue of the nasal cavity with an adjuvant activity, and offer a way for peptide delivery into the brain and the systemic circulation, in addition to their potential for brain tumor treatment. This review article aims at discussing the potential benefit of the intranasal nanoparticulate systems, including nanosuspensions, lipid and surfactant, and polymer-based nanoparticles as regards productive intranasal delivery. The aim of this review is to focus on the topicalities of nanotechnology applications for intranasal delivery of local, systemic, brain, and vaccination purposes during the last decade, referring to the factors affecting delivery, regulatory aspects, and patient expectations. This review further identifies the benefits of applying the Quality by Design approaches (QbD) in product development. According to the reported studies on nanotechnology-based intranasal delivery, potential attention has been focused on brain targeting and vaccine delivery with promising outcomes. Despite the significant research effort in this field, nanoparticle-based products for intranasal delivery are not available. Thus, further efforts are required to promote the introduction of intranasal nanoparticulate products that can meet the requirements of regulatory affairs with high patient acceptance.

3D-printed electrospinning setup for the preparation of loratadine nanofibers with enhanced physicochemical properties.

This study investigates the effects of drug-loaded nanofibers on the solubility of the poorly water-soluble drug, loratadine. Amorphous morphologies of electrospun loratadine nanofibers were prepared using a low-cost 3D-printed electrospinning setup with counter-flow air for the rapid production of nanofibers. Polyvinylpyrrolidone was used as a carrier polymer and ethanol as a solvent in the solution preparation. The prepared nanofibers were characterized by scanning electron microscopy, differential scanning calorimetry, X-ray diffraction analysis, Fourier transform infrared spectroscopy, solubility and in vitro dissolution studies with kinetic behavior evaluation. The scanning electron microscope images showed smooth nanofiber surfaces with a mean diameter of 372 nm. Moreover, both differential scanning calorimetry and X-ray diffraction analysis confirmed the amorphous state of the prepared nanofibers. FT-IR results suggested that loratadine lost its original crystal structure by hydrogen bonding interactions. The fabricated nanofibrous drug samples demonstrated a remarkable 26-fold increase in solubility when compared to the pure drug in phosphate buffer at pH 7.4. Furthermore, dissolution studies showed that 66% of the drug from the nanofibrous mat was released in the first 10 min, which is significantly higher than the maximum of 4% drug release of the reference samples within the same time. Thus, Loratadine nanofibers can be considered as an alternative dosage form with improved physicochemical properties.

Design and characterization of loratadine nanosuspension prepared by ultrasonic-assisted precipitation.

Nanoparticle engineering is a well-defined technique employed as a novel and effective method in drug design and delivery. It is widely used to control particle size, as well as the morphological and physicochemical properties of active pharmaceutical ingredients. Furthermore, it serves as a method of pre-dispersion preparation for various dosage form developments. Nanotechnology produces nanomaterials with enhanced properties in terms of solubility, dissolution and permeability. In this work, ultrasonic-assisted precipitation was employed to produce nanosuspensions of poorly water-soluble loratadine, using different stabilizers. The objective of our study was attempting to prepare solid nanoparticles of loratadine to be used as a possible intermediate for designing various dosage forms. The effects of the type(s) and concentration(s) of stabilizer(s) on mean particle size were assessed. Optimal process parameters required to produce homogeneous nanoparticles with particle size below 500 nm and polydispersity less than 0.3 were determined both for precipitation and ultrasonication. Pre-dispersions were evaluated for their particle size, polydispersity index and zeta potential. Freeze-drying was employed to produce dry nanoparticles. Particle size, particle size distribution and zeta potential of the dried nanoparticles were measured after reconstitution in water. Besides thermal analysis using DSC and structural analyses (XRPD and FT-IR), the morphological characteristics and dissolution behaviors were also investigated. The selected freeze-dried nanoparticles had a mean particle size range of 353-441 nm, a polydispersity index ranging between 0.167 and 0.229 and a zeta potential between -25.7 and -20.7 mV. These results suggest that material and process parameters were successfully optimized. DSC and XRPD spectra confirmed interactions between the formulation's components during freeze-drying. The solid nanoparticles showed 30-42% of cumulative release after 10 min compared to less than 1% of dissolution characterizing loratadine without pre-processing. This study demonstrates that preparing dried loratadine nanoparticles suitable for designing effective drug preparations is a feasible approach.