Showing papers by "Hibah M. Aldawsari published in 2019"

Fabrication, Optimization, and Evaluation of Rotigotine-Loaded Chitosan Nanoparticles for Nose-To-Brain Delivery.

Abstract: The objective of the present study was to develop, optimize, and evaluate rotigotine-loaded chitosan nanoparticles (RNPs) for nose-to-brain delivery. Rotigotine-loaded chitosan nanoparticles were prepared by the ionic gelation method and optimized for various parameters such as the effect of chitosan, sodium tripolyphosphate, rotigotine concentration on particle size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The prepared nanoparticles were characterized using photon correlation spectroscopy, transmission electron microscopy, scanning electron microscopy, atomic force microscopy, fourier-transform infrared spectroscopy, and X-ray diffraction. The developed RNPs showed a small hydrodynamic particle size (75.37 ± 3.37 nm), small PDI (0.368 ± 0.02), satisfactory zeta potential (25.53 ± 0.45 mV), and very high entrapment efficiency (96.08 ± 0.01). The 24-h in vitro release and ex vivo nasal permeation of rotigotine from the nanoparticles were 49.45 ± 2.09% and 92.15 ± 4.74% while rotigotine solution showed corresponding values of 95.96 ± 1.79%and 58.22 ± 1.75%, respectively. The overall improvement ratio for flux and permeability coefficient were found to be 4.88 and 2.67 when compared with rotigotine solution. A histopathological study showed that the nanoparticulate formulation produced no toxicity or structural damage to nasal mucosa. Our results indicated that rotigotine-loaded chitosan nanoparticles provide an efficient carrier for nose-to-brain delivery.

Preparation, Optimization, and Evaluation of Hyaluronic Acid-Based Hydrogel Loaded with Miconazole Self-Nanoemulsion for the Treatment of Oral Thrush.

Abstract: Miconazole nitrate (MZ) is a BCS class II antifungal poorly water-soluble drug with limited dissolution properties and gastrointestinal side effects. Self-nanoemulsifying delivery system-based gel of MZ can improve both solubility and oral mucosal absorption with enhanced antifungal activity. The study aims to formulate MZ self-nanoemulsion (MZ-NE) and combine it within hyaluronic acid-based gel. MZ solubility in various oils, surfactants, and cosurfactant used in NE formulations were evaluated. Mixture design was implemented to optimize the levels of NE components as a formulation variable to study their effects on the mean globule size and antifungal inhibition zones. Further, the optimized MZ-NE was loaded into a hyaluronic acid gel base. Rheological behavior of the prepared gel was assessed. Ex vivo permeability of optimized formulation across buccal mucous of sheep and inhibition against Candida albicans were examined. Mixture design was used to optimize the composition of MZ-NE formulation as 22, 67, and 10% for clove oil, Labrasol, and propylene glycol, respectively. The optimized formulation indicated globule size of 113 nm with 29 mm inhibition zone. Pseudoplastic flow with thixotropic behavior was observed, which is desirable for oral gels. The optimized formulation exhibited higher ex vivo skin permeability and enhanced antifungal activity by 1.85 and 2.179, respectively, compared to MZ-SNEDDS, and by 1.52 and 1.72 folds, respectively, compared to marketed gel. Optimized MZ-NE hyaluronic acid-based oral gel demonstrated better antifungal activity, indicating its potential in oral thrush pharmacotherapy.

Neuroprotective and Antioxidant Effect of Naringenin-Loaded Nanoparticles for Nose-to-Brain Delivery.

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder resulting in a decreased nigrostriatal availability of dopamine. Oxidative stress is one factor contributing to PD. Naringenin (NAR), a flavonoid, is a potent antioxidant shown to be beneficial in experimental PD. The clinical development of NAR has been hampered due to its low bioavailability resulting from gastrointestinal degradation, inefficient permeability, and low aqueous solubility. The objective of the present research was to formulate and characterize naringenin-loaded chitosan nanoparticles (NAR NPs) for nose-to-brain delivery. The cellular uptake, cytotoxicity, and neuroprotective effects of NAR NPs were determined using the SH-SY5Y cell line in vitro. NAR NPs were prepared using the ionic gelation method and characterized by zetasizer, transmission electron microscopy (TEM), and field emission microscopy (FESEM). The average particle size, polydispersity index (PDI), zeta potential, entrapment efficiency, and 24 h in vitro release profile were 87.6 ± 8.47 nm, 0.31 ± 0.04, 15.36 ± 2.05 mV, 91.12 ± 2.99%, and 54.80 ± 4.22%, respectively. The percentage NAR permeation through nasal mucosa from NPs was found to be 67.90 ± 0.72%. Cellular uptake of prepared NPs was confirmed by fluorescence microscopy. Neuroprotective activity of NAR NPs was evaluated through viability assays and by estimating reactive oxygen species (ROS) levels. NAR NPs showed enhanced neuroprotective ability and antioxidant effect against 6-OHDA-induced neurotoxicity in SH-SY5Y cells. However, animal studies are necessary to establish the potential of NAR NPs to be an effective carrier for the treatment of PD for nose-to-brain delivery.

Encapsulation of Lovastatin in Zein Nanoparticles Exhibits Enhanced Apoptotic Activity in HepG2 Cells.

Abstract: Research on statins highlights their potent cytotoxicity against cancer cells and their potential for cancer prevention. The aim of the current study was to examine whether loading lovastatin (LVS) in zein (ZN) nanoparticles (NPs) would potentiate the anti-proliferative effects of LVS and enhance its proliferation-inhibiting activity in HepG2 cells. LVS-ZN NPs were prepared and showed excellent characteristics, with respect to their particle size, zeta potential, diffusion, and entrapment efficiency. In addition, they showed the most potent anti-proliferative activity against HepG2 cells. ZN alone showed an observable anti-proliferative that was significantly higher than that of raw LVS. Furthermore, LVS uptake by HepG2 cells was greatly enhanced by the formulation in ZN. A cell cycle analysis indicated that LVS induced a significant cell accumulation in the G2/M and pre-G phases. In this regard, the LVS-ZN NPs exhibited the highest potency. The accumulation in the pre-G phase indicated an enhanced pro-apoptotic activity of the prepared formula. The cells incubated with the LVS-ZN NPs showed the highest percentage of cells with annexin-V positive staining. In addition, the same incubations showed the highest content of caspase-3 enzyme in comparison to raw LVS or ZN. Thus, the loading of LVS in ZN nanoparticles enhances its anti-proliferative activity against HepG2 cells, which is attributed, at least partly, to the enhanced cellular uptake and the induction of apoptosis.

Optimization of the Conditions for Plasmid DNA Delivery and Transfection with Self-Assembled Hyaluronic Acid-Based Nanoparticles.

Abstract: Polymeric systems have been extensively studied as polyelectrolyte complexes to enhance the cellular delivery and transfection efficiency of genetic materials, such as plasmid DNA (pDNA). Here, self-assembled nanoparticles were formulated by complexation of hyaluronic acid (HA)-conjugated poly(ethylene glycol) (HA–PEG) and poly(ethylenimine) (HA–PEI), respectively, with pDNA creating relatively small, stable, and multifunctional nanoparticle complex formulations with high transfection efficiency. This formulation strategy offers high gene expression efficiency and negligible cytotoxicity in HeLa and A549 human lung cancer cell lines. To develop the ideal formulation, in vitro transfection efficiency was studied for three different nanoparticle formulations (HA–PEI/HA–PEG, HA–PEI, and HA–PEG) with different concentrations. The combination of the three polymers (HA, PEG, and PEI) was significant for the formulation to achieve the maximum gene expression results. The nanoparticles were found to be stable for...