Breast cancer is the most widespread cancer in women with rising incidence, prevalence, and mortality in developed regions. Most breast cancers (80%) are estrogen receptor–positive, indicating that disease progression could be controlled by estrogen inhibition in the breast tissue. However, drug resistance limits the benefits of this approach. Combinatorial treatment could overcome the resistance and improve the outcome of breast cancer treatment. In the current study, we prepared letrozole-(LTZSPs) and quercetin-loaded spanlastics (QuSPs) using different edge activators—Tween 80, Brij 35, and Cremophor RH40—with different concentrations. The spanlastics were evaluated for their average particles size, surface charge, and percent encapsulation efficiency. The optimized formulations were further examined using transmission electron microscopy, Fourier transform infrared spectroscopy, in vitro drug release and ex vivo skin permeation studies. The prepared spherical LTZSPs and QuSPs had average particle sizes ranged between 129–310 nm and 240–560 nm, respectively, with negative surface charge and high LTZ and Qu encapsulation (94.3–97.2% and 97.9–99.6%, respectively). The in vitro release study of LTZ and Qu from the selected formulations showed a sustained drug release for 24 h with reasonable flux and permeation through the rat skin. Further, we evaluated the in vitro cytotoxicity, cell cycle analysis, and intracellular reactive oxygen species (ROS) of the combination therapy of letrozole and quercetin either in soluble form or loaded in spanlastics against MCF-7 breast cancer cells. The LTZSPs and QuSPs combination was superior to the individual treatments and the soluble free drugs in terms of in vitro cytotoxicity, cell cycle analysis, and ROS studies. These results confirm the potential of LTZSPs and QuSPs combination for transdermal delivery of drugs for enhanced breast cancer management.

Eye inflammation is considered one of the most common co-morbidities associated with ocular disorders and surgeries. Conventional management of this condition with non-steroidal anti-inflammatory drugs as eye drops is associated with low corneal bioavailability and ocular irritancy. In the current study, we first investigated the capacity of different solvent systems to enhance the solubility of Meloxicam (MLX). Then, we prepared chitosan nanoparticles loaded with meloxicam (MLX-CS-NPs) through electrostatic interaction between the cationic chitosan and the anionic MLX using either 100% v/v polyethylene glycol 400 or 0.25% w/v tripolyphosphate solution as solvents based on the MLX solubility data. In further studies, MLX-CS-NPs were characterized in vitro and assessed for their ex vivo corneal and scleral permeability. The morphology, average particle size (195–597 nm), zeta potential (25–54 mV), and percent entrapment efficiencies (70–96%) of the prepared MLX-CS-NPs were evaluated. The in vitro release study of MLX from the selected MLX-CS-NPs showed a sustained drug release for 72 h with accepted flux and permeation through the cornea and sclera of rabbits. In the in vivo studies, MLX-CS-NPs eye drop dispersion showed enhanced anti-inflammatory activity and no ocular irritancy compared to MLX-eye drop solution. Our findings suggest the potential for using chitosan nanotechnology for ocular delivery of MLX with high contact time and activity.

Background: Inflammation is the keystone in the disease’s pathological process in response to any damaging stimuli. Therefore, any agent that inhibits the inflammatory response is under focus, either a drug or a bioactive compound. Selenium nanoparticles have drawn attention in various biomedical applications, including the anti-inflammatory activity. Purpose: In the current study, we aimed to evaluate the capacity of different surface coating materials (soybean lecithin, PEG 6000, and β-cyclodextrin) to enhance the anti-inflammatory activity of the synthesized selenium nanoparticles (SeNPs). The capability of the coated SeNPs to adsorb indomethacin (IND) on their surfaces compared to the uncoated SeNPs was also evaluated. Methods: SeNPs were synthesized, coated with different materials, and characterized in vitro using X-ray diffraction, UV-Vis spectrophotometer, FTIR, SEM, TEM, and particle size and zeta potential measurements. The in vivo anti-inflammatory activity of the uncoated/coated SeNPs loaded into hydrogel was evaluated using a carrageenan-induced paw edema rat model. The effect of SeNPs surface coatings was further evaluated for IND loading capacity. Results: Our findings proved the superior anti-inflammatory activity of all coated SeNPs compared to the uncoated SeNPs, especially with β-cyclodextrin surface coating. Regarding the IND loading capacity of the prepared uncoated/coated SeNPs, the amount of drug loaded was 0.12, 1.12, 0.3, and 0.14 μg IND/μg SeNPs for the uncoated, lecithin-, PEG- and β-CD-coated SeNPs, respectively. Conclusion: Surface functionalization of SeNPs can provide a synergistic therapeutic activity. Our results are promising for further investigation of the in vivo anti-inflammatory synergistic activity of the IND-loaded surface-coated SeNPs. Graphical Abstract:

Optimizing a sustained-release drug delivery system for the treatment of cystic fibrosis is crucial for decreasing the dosing frequency and improving patients’ compliance with the treatment regimen. In the current work, we developed an injectable PLGA microparticle formulation loaded with ivacaftor, a CFTR potentiator that increases the open probability of the CFTR anion channel, using a single emulsion solvent evaporation technique. We aimed to study the effect of different parameters on the characteristics of the prepared formulations to select an optimized microparticle formulation to be used in the in vivo pharmacokinetic study in mice. First, ivacaftor-loaded microparticles were prepared while varying the formulation parameters to study their effect on the formulations’ size, morphology, drug loading, encapsulation efficiency, and in vitro release profiles. All the prepared microparticles showed smooth spherical surfaces with internal diameters of 1.91– 6.93 µm, drug loading (DL) of 3.91 – 10.3%, percent encapsulation efficiencies (%EE) of 26.6 – 100%, and an overall slow cumulative release profile. We selected one formulation that showed the best combined %DL and %EE values (8.25, and 90.7%, respectively), with an average particle size of 6.83 µm, and a slow bi-phasic in vitro release profile (up to 6 weeks) to study its in vivo pharmacokinetics in comparison to solubilized ivacaftor following their subcutaneous (SC) and intravenous (IV) administration to mice, respectively. The injected microparticle formulation showed steady plasma levels of ivacaftor over a period of 28 days, and a 6-fold increase in AUC _{0 – t} (71.6 µg/mL*h) compared to the intravenously injected soluble ivacaftor (12.3 µg/mL*h). Our results suggest that this novel ivacaftor-loaded microparticle formulation could potentially eliminate the need for the frequent daily administration of ivacaftor by people with cystic fibrosis which could improve their compliance and ensure successful treatment outcomes.