Novel Chitosan Nanoparticles Loaded with Methotrexate for Topical Treatment of Psoriasis.

AIMS: In this work, CS NPs were prepared by the ionic gelation method and encapsulated with MTX to treat psoriasis dermally. BACKGROUND: A major drawback of using MTX to treat psoriasis is its limited diffusion through the skin, which may cause insufficient penetration of MTX into the basal layer of the epidermis, where psoriatic cells are generated. OBJECTIVE: Nanoparticles have been used to enhance MTX diffusion through the skin. The system prepared in this work is expected to direct the drug to psoriasis cells by enhancing the drug diffusion through the skin, which will increase the amount of the drug reaching the epidermis. This is expected to enhance the effectiveness of the drug and to decrease its systemic side effects. METHODS: Five formulations of Chitosan nanoparticles were prepared and loaded with Methotrexate using the ionic gelation technique. Particle size, dispersity, charge, loading capacity and encapsulation efficacy were measured. Characterization of prepared nanoparticles was conducted to confirm the formation of CS-NPs, successful encapsulation of MTX and its compatibility with other formulation components. In vitro drug release from CS-NPs, its permeation and accumulation in rats' skin were explored. Finally, the anti-psoriatic activity was assessed using the "mouse tail model." RESULTS: The results showed that the sizes ranged from 132.13 ± 0.70 to 300.60 ± 4.81 nm, where SEM demonstrated the spherical and uniform distribution of the NPs. The surface charge of all NPs was highly positive and ranged from 20.22 ± 1.10 to 30.90 ± 0.70 mV. Further, the EE% and LC% of the nanoparticles were in the range of 77.72%-92.70% and 17.90%-21.81%, respectively. in vitro, the release of methotrexate from the nanoparticles was sustained. Additionally, both the permeation and retention of drugs within the skin were enhanced significantly using this system. Eventually, orthokeratosis% and drug activity% showed significant superiority of MTX-CS NPs over the free drug in treating psoriasis in model mice. CONCLUSION: In conclusion, MTX-CS NPs can be used to enhance the treatment of psoriasis topically.

Insights into the mapping of green synthesis conditions for ZnO nanoparticles and their toxicokinetics.

Research on ZnO nanoparticles (NPs) has broad medical applications. However, the green synthesis of ZnO NPs involves a wide range of properties requiring optimization. ZnO NPs show toxicity at lower doses. This toxicity is a function of NP properties and pharmacokinetics. Moreover, NP toxicity and pharmacokinetics are affected by the species type and age of the animals tested. Physiologically based pharmacokinetic (PBPK) modeling offers a mechanistic platform to scrutinize the colligative effect of the interplay between these factors, which reduces the need for in vivo studies. This review provides a guide to choosing green synthesis conditions that result in minimal toxicity using a mechanistic tool, namely PBPK modeling.

Polymeric Nanoparticles for Inhaled Vaccines.

Many recent studies focus on the pulmonary delivery of vaccines as it is needle-free, safe, and effective. Inhaled vaccines enhance systemic and mucosal immunization but still faces many limitations that can be resolved using polymeric nanoparticles (PNPs). This review focuses on the use of properties of PNPs, specifically chitosan and PLGA to be used in the delivery of vaccines by inhalation. It also aims to highlight that PNPs have adjuvant properties by themselves that induce cellular and humeral immunogenicity. Further, different factors influence the behavior of PNP in vivo such as size, morphology, and charge are discussed. Finally, some of the primary challenges facing PNPs are reviewed including formulation instability, reproducibility, device-related factors, patient-related factors, and industrial-level scale-up. Herein, the most important variables of PNPs that shall be defined in any PNPs to be used for pulmonary delivery are defined. Further, this study focuses on the most popular polymers used for this purpose.

Microneedle-assisted transdermal delivery of amlodipine besylate loaded nanoparticles.

Transdermal drug delivery has been developed to increase drug bioavailability and improve patient compliance. The current study was carried out to formulate and evaluate a transdermal delivery system loaded with biodegradable polymeric nanoparticles for sustained delivery of amlodipine besylate (AMB). For this purpose, AMB was incorporated into CS nanoparticles that were prepared via the ionic gelation method. Three formulations containing different blends of CS and tripolyphosphate were investigated for the preparation of the nanoparticles and evaluated for particle size (PS), zeta potential (ZP), loading capacity (LC), encapsulation efficiency (EE), scanning electron microscope (SEM), and drug release kinetics. The smallest observed particle size was 321.14 ± 7.21 nm (NP-3). Across all formulations, the highest observed EE% was 87.2 ± 0.12% (NP-2), and the highest observed LC% was 60.98 ± 0.08% (NP-2). Microneedles were formed by using 15% polyvinylalcohol (PVA) (F1), 15% PVA with 1% propylene glycol (PG) (F2), and 15% PVA with 5% PG (F3). On investigating drug release rates, it was observed that drug permeation and steady-state flux (Jss) both increased proportionally with increasing PG concentration. Nanomedicine, when combined with physical techniques, has opened new opportunities for the growth and development of transdermal delivery systems in the pharmaceutical industry. In conclusion, biodegradable polymeric nanoparticles loaded in hydrogel microneedles served as a potential system for the transdermal delivery of AMB in a controlled manner.

Formulation and characterization of tobramycin-chitosan nanoparticles coated with zinc oxide nanoparticles.

Herein we describe the preparation, characterization and the antibacterial effect of Tobramycin-chitosan nanoparticles (TOB-CS NPs) coated with zinc oxide nanoparticles (ZnO NPs). Four formulations of TOB-CS NPs (A-D) were prepared to study the effect of experimental variables on the NPs behavior. Two formulations of ZnO NPs were prepared using the solvothermal and the precipitation methods (ZnO1 and ZnO2), and then characterized. TOB-CS NPs (Formula d) was coated with the ZnO1. Moreover, the antibacterial activity of TOB-CS NPs, ZnO NPs and the coated nanoparticles against S. aureus and E. coli was examined. Changing the variables in preparing TOB-CS NPs resulting in variabilities in sizes (297.6-1116.3 nm), charges (+8.29-+39.00 mV), entrapment (51.95-90.60%). Further, TOB release was sustained over four days. ZnO NPs have sizes of 47.44 and 394.4 nm and charges of -62.3 and 89.4 mV when prepared by solvothermal and precipitation technique, respectively. Coated TOB-CS NPs had a size of 342 nm, a charge of +4.39 and released 100 µg/ mL of the drug after four days. The antimicrobial activity of TOB-CS NPs was lower than free TOB against S. aureus and E. coli. The coated NPs showed higher antimicrobial effect in comparison to formula D and ZnO1. In conclusion, coating TOB-CS NPs with ZnO NPs exhibited a great antibacterial effect that may be sustained for days.

Preparation and Characterization of Docetaxel-PLGA Nanoparticles Coated with Folic Acid-chitosan Conjugate for Cancer Treatment.

The conjugation of chitosan (CS) and folic acid (FA) was prepared and used to coat PLGA nanoparticles (NPs) that are loaded with Docetaxel (DTX) to target cancer cells that have lower pH and overexpression of folate receptors in comparison to normal cells. Three formulations had been prepared to reach the highest loading capacity (LC%) and encapsulation efficiency (EE%) and to study the effect of the amount of FA-CS on the drug release. The sizes, charges, homogeneity, surface morphology, LC% and EE% of the NPs were determined. The NPs were characterized using FTIR and XRD. In vitro release profiles of DTX from PLGA NPs, at pH 5.5 and 7.4 were determined. Finally, in vitro cytotoxicity assay on three cancer cell lines (RPMI 2650, Calu-3, and A549) was studied. The sizes of the three formulations ranged between 250.3±1.7 and 356.3±17.7. All prepared formulations showed acceptable monodispersity with highly positive charges. The EE% was above 85% and the LC% ranged between 6-35%. The in vitro release of DTX show an inverse relation to the amounts of FA-CS used and the pH of the dissolution medium. Coated PLGA NPs showed a significant difference in RPMI 2650, Calu-3, and A549 cell viability in comparison to free DTX. The NPs components were safe and non-toxic to human cells. In conclusion, coating PLGA NPs with FA-CS may be used as a good carrier for chemotherapeutic agents that selectively target carcinogenic tissues.

Awareness about nanotechnology and its applications in drug industry among pharmacy students.

INTRODUCTION: Given the multiple nanotechnology-based pharmaceutical products that are available on the drug market, nanotechnology education has to be offered within pharmacy undergraduate curricula. METHODS: A cross-sectional study was carried out to assess the level of nanotechnology awareness among pharmacy students using two questionnaires. The study targeted 500 students and the deans of the faculties of pharmacy in Jordan. RESULTS: Results show that most of the students had poor knowledge about nanotechnology and that academic courses are the leading source of information. <10% of students attended experiments related to nanotechnology. About 50% of students did not have any knowledge about the safety of nanotechnology. All the deans stated that there is no specific practical or theoretical course to teach nanotechnology, but the concepts are taught within other courses. CONCLUSIONS: Pharmacy students' knowledge about nanotechnology is poor, and courses within pharmacy curricula need to be dedicated to teaching nanotechnology and its applications.

Preparation and characterization of insulin chitosan-nanoparticles loaded in buccal films.

Chitosan nanoparticles loaded with insulin (IN-CS-NPs) were prepared using ionic gelation method using sodium tripolyphophate as a crosslinker. Later the nanoparticles (NPs) were dispersed in buccal films. The physicochemical properties and the morphology of the nanoparticles were characterized. The stability and release of insulin from the NPs were investigated. Buccal films were prepared separately and their properties such as the weight, thickness, pH, and mucoadhesiveness were investigated. The best film was used to disperse IN-CS-NPs and the loaded film was characterized. The nanoparticles size, polydispersity index, zeta potential, entrapment efficacy, and the loading capacity were 325.07 ± 1.32 nm, 0.38 ± 0.03 and 8.41 ± 0.80 mV, and 73.27 and 18.03%, respectively. The weight and thickness of the loaded film with IN-CS-NPs were 23.0 ± 3.0 mg and 0.32 ± 0.04 mm, respectively and the mucoadhesive force was 2.3 ± 0.2 N. The drug was stable in the NPs and in the films for three months, and its release was controlled by the film and the nanoparticles. Finally, the films loaded with IN-CS-NPs were studied in vivo and were compared to the commercially available insulin. The films prepared in this work were found to decrease glucose level significantly in diabetic rats.

Synthesis and characterization of photocatalytic polyurethane and poly(methyl methacrylate) microcapsules for the controlled release of methotrexate.

The aim of this work is to prepare ultraviolet (UV) triggered controlled release of compounds from microcapsule systems (MCs). Polyurethane (PU) and poly(methyl methacrylate) (PMMA) microcapsules were studied with/without chemical functionalization using photocatalytic TiO2 nanoparticles (NPs) on their surface. Once TiO2 nanoparticles are illuminated with UV light (λ = 370 nm), they initiate the rupture of the polymeric bonds of the microcapsule and subsequently initiate the encapsulated compound release, methotrexate (MTX) or rhodamine (Rh), in the present work. The size, polydispersity, charge, and yield of all MCs were measured, being the methotrexate drug release for all systems determined and compared with and without functionalization with TiO2 NPs, under dark, visible light and UV illumination in vitro. Finally, the Rh release was characterized using fluorescence microscopy. The TiO2 NPs size is around 10 nm, as determined by X-ray diffraction experiments. The PU MCs average size is around 60 µm, its electric charge +3.11 mV and yield around 85%. As for the PMMA MCs, the average size is around 280 µm, its electric charge -7.2 mV and yield around 25% and 30% for both MTX and Rh, respectively. In general, adding TiO2 NPs or the encapsulated products to the MCs does not affect the size but functionalization with TiO2 NPs lowers the electric charge. Microcapsules functionalized with TiO2 nanoparticles and irradiated with UV light presented the highest release of MTX and Rh. All other samples showed lower drug release levels when studied under the same conditions.

Low Molecular Weight Chitosan-Coated PLGA Nanoparticles for Pulmonary Delivery of Tobramycin for Cystic Fibrosis.

(1) Background: Poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) loaded with Tobramycin were prepared using a solvent-evaporation method. (2) Methods: The NPs were coated with low molecular weight chitosan (LMWC) to enhance the mucoadhesiveness of PLGA-NPs. The following w/w ratios of tobramycin to LMWC were prepared: control (0:0.50), F0 (1:0.25), F0.5 (1:0.5), and F1 (1:1). (3) Results: The results showed that the size of the particles increased from 220.7 nm to 575.77 nm as the concentration of LMWC used in the formulation increased. The surface charge was also affected by the amount of LMWC, where uncoated-PLGA nanoparticles had negative charges (-2.8 mV), while coated-PLGA NPs had positive charges (+33.47 to +50.13 mV). SEM confirmed the size and the spherical homogeneous morphology of the NPs. Coating the NPs with LMWC enhanced the mucoadhesive properties of the NPs and sustained the tobramycin release over two days. Finally, all NPs had antimicrobial activity that increased as the amount of LMWC increased. (4) Conclusion: In conclusion, the formulation of mucoadhesive, controlled-release, tobramycin-LMWC-PLGA nanoparticles for the treatment of P. aeruginosa in cystic fibrosis patients is possible, and their properties could be controlled by controlling the concentration of LMWC.

Formulation and characterization of acetaminophen nanoparticles in orally disintegrating films.

The purpose of this study was to prepare orally disintegrating films containing nanoparticles loaded with acetaminophen. Nanoparticles were prepared by the emulsion-solvent evaporation method where acetone phase containing acetaminophen and poly(lactide-co-glycolide acid) (PLGA) was added to water phase containing hydroxypropyl methyl cellulose, poly ethylene glycol, polyvinyl alcohol (PVA) and aspartame in a rate of 1.5 drop s(-1) and agitated at 1200 rpm. The size, polydispersity index (PI) and drug entrapment (DE) were measured. The emulsions were cast to form films, which were evaluated physico-mechanically. The effect of different degrees of hydrolization of PVA and polymerization of PLGA and the effect of different ratios of PVA to PLGA was studied. Films with acceptable physico-mechanical properties were further studied. The size and PI of the nanoparticles was dependent on PVA hydrolization, PLGA polymerization and the ratio of PVA to PLGA. All films disintegrated in less than one minute, but acetaminophen was not free in the dissolution media even after six days. These results may indicate that although the nanoparticles released from the films immediately when impressed in solution the drug is sustained in the nanoparticles for longer time, which is to be clarified in future work.