Formulation and evaluation of cyclodextrin-based nanosponges of griseofulvin as pediatric oral liquid dosage form for enhancing bioavailability and masking bitter taste.

The aim of this study was the development of griseofulvin (GRI) loaded ß-cyclodextrin (ß-CD) based nanosponges for bitter taste masking, improving dissolution rate and oral bioavailability. Plain NS (NS1 NS2 and NS3) were fabricated by reacting ß-CD with the cross-linker diphenyl carbonate at different molar ratios (1:2, 1:4 and 1:6, respectively) using ultrasonication method. The NS2 provided both highest %yield and GRI solubilization enhancement. Thus, the drug was loaded in NS2 at different NS2: drug weight ratios in presence or absence of 0.25%w/w polyvinylpyrolidone (PVP k30). The GRI loaded NS (F1) that provided highest drug loading capacity and entrapment efficiency (47.20 ± 0.38%, 84.91 ± 0.30%, respectively) was morphologically examined using scanning electron microscopy (SEM). Also, Particle size, zeta potential, differential scanning calorimetry (DSC), Fourier transform infra-red (FT-IR), nuclear magnetic resonance (NMR) spectroscopy, in-vitro release, taste masking potential were evaluated. Moreover, in-vivo Pharmacokinetic studies were performed on rats. The F1 showed particle size 665.9 ± 13.8 nm and zeta potential -21.5 ± 0.7 mV. The DSC and FT-IR analysis confirmed the complexation of GRI with NS2. Nanosponges (F1) provided 3.19, folds increase in dissolution efficiency %, 2.13 and 3.78 folds increase in Cmax and AUC0-48 compared to plain GRI. Taste masking evaluation confirmed the potential of GRI nanosponges (F1) in masking the bitter taste of GRI completely. The study confirmed that complexation of GRI with NS would be a viable approach for masking the bitter taste of GRI and improving oral bioavailability, that Cmax, Tmax and AUC 0-48 were significantly higher for the developed formulation (F1).

Fabrication Of Gold Nanoparticles In Absence Of Surfactant As In Vitro Carrier Of Plasmid DNA.

PURPOSE: This work aimed to synthesize surfactant-free AuNPs for targeted delivery of plasmid DNA encoded p53 gene and to avoid conventional production method of Gold nanoparticles (AuNPs) which may adversely affect the final shape, diversity, and size due to accumulation of the formulated surfactant - gold complex to the surface. METHODS: The AuNPs were fabricated using seeded-growth method with L-Cystine methyl ester hydrochloride as capping agent, then loaded with plasmid DNA encoded p53 gene. The resultant AuNPs and AuNPs-p53 complex were evaluated for physical characteristics and morphology. Confirmation of complex formation was performed using gel electrophoresis. Furthermore, the efficient delivery and cytotoxicity behavior of the encoded gene were examined on both healthy lung cells (WI38) and cancerous lung cells (A549). RESULTS: L-cysteine methyl ester hydrochloride AuNPs showed acceptable physical characteristics (30 nm, +36.9 mv, and spherical morphology). P53 attachment to AuNPs was confirmed by gel electrophoresis. The RT-PCR proved the overexpression of p53 by the fabricated AuNPs-p53 complex. The high percentage of cell viability in normal lung cell line (WI 38) proved the safety of L-cysteine methyl ester functionalized AuNPs. Additionally, the apoptotic effect due to expression of p53 gene loaded on AuNPs was only prominent in lung cancer cell line (A549), revealing selectivity and targeting efficiency of anticancer AuNPs-p53 complex. CONCLUSION: AuNPs can be considered as a potential delivery system for effective transfection of plasmid DNA which can be used for successful treatment of cancer.

Transdermal patches loaded with L-cysteine HCL as a strategy for protection from mobile phone emitting electromagnetic radiation hazards.

Mobile phone usage has been increased in the last few years emitting electromagnetic radiation (EMR), which disturbs normal cellular processes via oxidative stress. L-cysteine, a glutathione precursor, prevents oxidative damage. Transdermal patches (TDPs) loaded with L-cysteine hydrochloride (L-CyS-HCL) were fabricated by dispersion of L-CyS-HCL 5% w/w and different concentrations of sorbitol as a plasticizer in room-temperature vulcanizable synthetic silicone matrices (RTV-Si). The effect of sorbitol on patch physicochemical parameters was assessed; in-vitro L-CyS-HCL release profiles and ex-vivo permeation were studied. Pharmacokinetic parameters of endogenous synthetized in-vivo glutathione, after receiving IV bolus dose of L-CyS-HCl and L-CyS-HCl-RTV-Si-TDPs were studied in rat model. The influence of L-CyS-HCL-RTV-Si-TDPs against damaging effects of mobile phone EMR on rats' blood and brain tissues was studied. The results revealed that patch plasticity, intensity reflections, surface porosity, L-CyS-HCL release rate and skin permeation increased with increasing sorbitol concentration. Pharmacokinetic profile for IV dose and L-CyS-HCl-RTV-Si-TDPs revealed that the L-CyS-HCl-RTV-Si-TDPs provided a sustained glutathione plasma concentration-time profile over entire patch application. High significant differences in biological parameters (blood and brain samples) were observed for radiated rats using the patch in study compared with positive control rats. Promising long-term strategy for protection against mobile phone hazards was obtained.

Pulmonary Delivery of Isoniazid in Nanogel-Loaded Chitosan Hybrid Microparticles for Inhalation.

PURPOSE: Inhalable pulmonary delivery of isoniazid (INH) may improve the efficacy and reduce drug resistance. METHOD: INH-loaded chitosan microparticles (Cs-Mps-1-3) were prepared as an inhalable carrier for the previously prepared INH-loaded polyvinylpyrrolidone/polyitaconic acid nanoparticles (NPs) using spray-drying technique. Here, Cs-Mps-1-3 are composed of Cs: INH-loaded NPs: Free INH at w/w ratios (1:1:0), (1: 0:1), and (1:1:1), respectively. Subsequently, the prepared Cs-Mps-1-3 characterizations were studied. RESULTS: Cs-Mps-1-3 showed a spherical, smooth, positively charged surface (ζ-potential values +20.2, +28.7, and +22.6) and a size range 1.52-3.12 µm. In addition, Carr's compressibility indices of Cs-Mps-1-3 were 32.5%, 24.8%, and 28.02%, respectively. The in vitro INH released showed good correlation with first-order pattern, with predominance of the diffusion-controlled mechanism. In vitro aerodynamic deposition of Cs-MPs-3 possessed 56.81% effective fine particle fraction with lower impaction loss and device retention (10.47% and 30.9% at mouth and throat and at stage 1, respectively). The minimum inhibitory concentration of Cs-Mps-3 displayed 63-fold more inhibition effects on Mycobacterium tuberculosis than INH solution, owing to the combined effect of positively charged Cs-Mps with their facilitating bacterial cell surface binding and cellular penetration activity of NPs. CONCLUSION: The promising potential of Cs-Mps-3 as an inhalable carrier for pulmonary delivery of INH is recommended.

Correction to: Preparation and Optimization of Fast-Disintegrating Tablet Containing Naratriptan Hydrochloride Using D-Optimal Mixture Design.

During the production process, an editorial error occurred where the typesetter placed the ± symbol on the right side of the values in Table IV, whereas the symbol should be placed on the left side. The original article has been corrected.

Preparation and Optimization of Fast-Disintegrating Tablet Containing Naratriptan Hydrochloride Using D-Optimal Mixture Design.

Optimization of a lyophilized fast-disintegrating tablet (LFDT) formulation containing naratriptan hydrochloride, an antimigraine drug, was the foremost objective of the study, aiming in achieving fast headache pain relief. The Design-Expert® v10 software was used to generate formulations using D-optimal mixture design with four components: gelatin (X1), hydrolyzed gelatin (X2), glycine (X3), and mannitol (X4) of total solid material (TSM) w/w. The effect of the relative proportion of each component was determined on friability (Y1), hardness (Y2), and in vitro disintegration time (Y3), which was then applied for formulation optimization. In addition, their effect on tablet porosity was determined via scanning electron microscopy (SEM). Drug-excipient interaction was evaluated using differential scanning calorimetry (DSC). A comparative dissolution study against the conventional tablets was studied. Accelerated stability study was carried out in (Al/Al) and (Al/PVC) blister packs. An in vivo pharmacokinetic study was carried out to compare the optimized formulation and the conventional tablets. The optimized formulation's responses were 0.30%, 3.4 kg, and 6.12 s for Y1, Y2, and Y3, respectively. No drug-excipient interaction was specified via DSC. The optimized formulation exhibited porous structure as determined via SEM. Dissolution study demonstrated complete dissolution within 1.5 min. Study indicated stability for 78 months in (Al/Al) blister packs. In vivo pharmacokinetic study demonstrated that Cmax, AUClast, and AUCinf were significantly higher for the developed formulation. As well, the Tmax was 1 h earlier than that of convenient tablet. An LFDT would achieve a faster onset of action for naratriptan compared to other formulations.

Design of Isoniazid Smart Nanogel by Gamma Radiation-Induced Template Polymerization for Biomedical Application.

PURPOSE: Preparation of Isoniazid (INH) loaded nanogel particles using gamma radiation as safe, simple, cheap and reproducible technique for promoting mycobacterial killing in a lower-dose system aiming in developing of drug resistance. METHODS: Polymeric pH-sensitive nanogels were prepared by gamma radiation-induced polymerization of Acrylic acid (AAc) or Itaconic acid (IA), in aqueous solution of polyvinylpyrrolidone (PVP), as template polymer. The prepared nanogels were utilized for encapsulation of INH. 31X22 factorial design was employed for optimization and exploring the effect of radiation dose (X1) (30-50kGy), ratio of PVP: acid (X2) (50:50-30:70) and type of acid (X3) on the prepared nanogel characterization RESULTS: The optimized levels of X1, X2 and X3 were (50 KGy, 30:70 and Itaconic acid, respectively), with a desirability of 0.959. In-vitro INH release rate from the prepared nanogels decreased with increasing gamma radiation doses, with the predominance of the diffusion mechanism for drug release pattern. In addition, it was perceived that the minimum inhibitory concentration (MIC) of INH loaded PVP/PIA nanogels on Mycobacteria Tuberculosis was 8 folds lower than that of INH solution. CONCLUSION: The prospective of PVP-K90/PIA was recommended as a smart candidate for delivery of INH with promising achievements against tuberculosis than free drug. Graphical abstract Mechanism of formation and loading of Isoniazid PVP/PIA nanogel.