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Purpose: The objective of this work was to formulate a delivery system of pDNA encoded p53 gene-loaded chitosan-sodium deoxycholate (CS-DS) nanoparticles, and to evaluate their influence on in vitro cytotoxicity and transfection efficiency of p53 gene. Methods: The prepared pDNA-loaded CS-DS nanoparticles were evaluated for morphology, particle size, zeta potential, entrapment efficiency %, in vitro release, in vitro cytotoxicity, and transfection efficiency. Results: The mean particle size ranged from from 96.5 ± 11.31 to 405 ± 46.39 nm. All nanoparticles had good positive zeta potential values. Entrapment efficiency % ranged from 38.25 ± 3.25 to 94.89 ± 5.67. The agarose gel electrophoresis confirmed the strong binding between plasmid and CS. The in vitro pDNA release from nanoparticles exhibited an initial burst effect followed by a sustained drug release over a period of 6 days. In vitro cytotoxicity against human Caco-2 cells showed low cell cytotoxicity of plain CS-DS nanoparticles, while pDNA-loaded CS-DS nanoparticles showed a cytotoxic effect with increasing nanoparticles' concentration. Gene transfection, analyzed by PCR and ELISA, showed a direct correlation between gene expression and concentration of pDNA. The highest expression of the gene was achieved with pDNA concentration of 9 µg/mL with 5.7 times increase compared to naked pDNA of the same concentration. Conclusion: The obtained results were very encouraging and offer an alternative approach to enhancing the transfection efficiency of genetic material-loaded chitosan-based delivery systems.

Background and purpose: Conventional topical ophthalmic aqueous solutions and suspensions are often associated with low bioavailability and high administration frequency, pulsatile dose and poor exposure to certain ocular parts. The aim of this study was to develop an ophthalmic nanoparticles loaded gel, for delivering prednisolone acetate (PA), to increase dosing accuracy, bioavailability, and accordingly, efficiency of PA in treating inflammatory ocular diseases. Methods: A novel formulation of self-assembled nanoparticles was prepared by the complexation of chitosan (CS) and, the counter-ion, sodium deoxycholate (SD), loaded with the poorly-water-soluble PA. Particle size, zeta potential, encapsulation efficiency (EE) and drug loading content (LC) of prepared nanoparticles were assessed. Moreover, the nanoparticles were characterized using differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR). Drug release and eye anti-inflammatory potential of the prepared novel formulation was investigated. Results: Mean particle size of the nanoparticles have dropped from 976 nm ±43 (PDI 1.285) to 480 nm ±28 (PDI 1.396) when the ratio of CS-SD was decreased. The incorporation of 0.1-0.3% of polyvinyl alcohol (PVA), in the preparation stages, resulted in smaller nanoparticles: 462 nm ±19 (PDI 0.942) and 321 nm ±22 (PDI 0.454) respectively. DSC and FTIR results demonstrated the interaction between CS and SD, however, no interactions were detected between PA and CS or SD. Drug release of PA as received, in simulated tears fluid (pH 7.4), showed a twofold increase (reaching an average of 98.6% in 24 hours) when incorporated into an optimized nanoparticle gel formulation (1:5 CS-SD). Conclusion: The anti-inflammatory effect of PA nanoparticles loaded gel on female guinea pig eyes was significantly superior to that of the micronized drug loaded gel (P < 0.05).

Hany SM Ali,1,2 Ahmed F Hanafy,1,3 Abdulmalik Alqurshi1 1Department of Pharmaceutics and Pharmaceutical Technology, College of Pharmacy, Taibah University, Al-Madinah Al-Munawwarah, Saudi Arabia; 2Department of Pharmaceutics, Faculty of Pharmacy, Assiut University, Assiut, Egypt; 3Research and Development Department, Al Andalous Pharmaceutical Industries, Cairo, Egypt Introduction: Presenting poorly water-soluble drugs as nanoparticles has shown to be an effective technique in enhancing drug dissolution rate, intrinsic solubility, and thus oral bioavailability. Nevertheless, working with nanoparticles introduces many challenges, one of which is their physical instability. Formulating nanoparticles into a solid dosage form may overcome such challenges and thus unlock the potential benefits of nanosizing. Methods: The current work investigates the possibility of developing a novel solid dosage form, with enhanced dissolution rate, whereby nanocrystals (~400nm) of the class II Biopharmaceutical Classification System drug, glyburide (GBD) were fabricated through combined precipitation and homogenization procedures. Using a novel, but scalable, spraying technique, GBD nanocrystals were loaded onto commonly used tablet fillers, water-soluble lactose monohydrate (LAC), and water insoluble microcrystalline cellulose (MCC). Conventional tableting processes were then used to convert the powders generated into a tablet dosage form. Results: Studies of redispersibility showed considerable preservation of size characteristics of GBD nanocrystals during downstream processing with redispersibility indices of 105 and 118 for GBD–LAC and GBD–MCC, respectively. Characterization by differential scanning calorimetry, powder X-ray diffraction, and scanning electron microscopy showed that the powders generated powders contained nanosized crystals of GBD which adhered to carrier surfaces. Powder flowability was characterized using Hausner ratio (HR) and Carr’s index (CI). GBD–LAC-loaded particles exhibited poor flowability with CI and HR of 37.5% and 1.60, respectively, whilst GBD–MCC particles showed a slightly improved flowability with CI and HR of 26.47% and 1.36, respectively. The novel tablet dosage form met US Pharmacopeia specifications, including drug content, hardness, and friability. Conclusion: Higher dissolution rates were observed from the nanocrystal-based tablets compared to the microsized and commercial drug formulations. Moreover, the novel nanocrystal tablet dosage forms showed enhanced in vivo performance with area under the plasma concentration–time curve in the first 24 hours values 1.97 and 2.24 times greater than that of marketed tablets. Keywords: glyburide, nanocrystals, downstream, tablet, bioavailability, solidification, redispersibility