Mesoporous silica nanoparticles functionalized with folic acid/methionine for active targeted delivery of docetaxel

Abstract: Mesoporous silica nanoparticles (MSNs) are known as carriers with high loading capacity and large functionalizable surface area for target-directed delivery. In this study, a series of docetaxel-loaded folic acid- or methionine-functionalized mesoporous silica nanoparticles (DTX/MSN-FA or DTX/MSN-Met) with large pores and amine groups at inner pore surface properties were prepared. The results showed that the MSNs were successfully synthesized, having good pay load and pH-sensitive drug release kinetics. The cellular investigation on MCF-7 cells showed better performance of cytotoxicity and cell apoptosis and an increase in cellular uptake of targeted nanoparticles. In vivo fluorescent imaging on healthy BALB/c mice proved that bare MSN-NH2 are mostly accumulated in the liver but MSN-FA or MSN-Met are more concentrated in the kidney. Importantly, ex vivo fluorescent images of tumor-induced BALB/c mice organs revealed the ability of MSN-FA to reach the tumor tissues. In conclusion, DTX/MSNs exhibited a good anticancer activity and enhanced the possibility of targeted drug delivery for breast cancer

Design and development of intraocular polymeric implant systems for long-term controlled-release of clindamycin phosphate for toxoplasmic retinochoroiditis

Background: The release of the anti-toxoplasmosis drug, clindamycin phosphate, from intraocular implants of the biodegradable polymers poly (D, L-lactic acid) (PLA) and poly (D, L-lactide-co-glycolide) (PLGA) has been studied in vitro. Materials and Methods: The preparation of the implants was performed by a melt-extrusion method. The developed extrudates were characterized and compared in in-vitro release profiles for elucidating the drug release mechanism. The formulations containing up to 40% w/w of drug were prepared. Release data in phosphate buffer (pH 7.4) were analyzed by high performance liquid chromatography. The release kinetics were fitted to the zero-order, Higuchi′s square-root, first order and the Korsmeyer-Peppas empirical equations for the estimation of various parameters of the drug release curves. Degradation of implants was also investigated morphologically with time (Scanning Electron Microscopy). Results: It was observed that, the release profiles for the formulations exhibit a typical biphasic profile for bulk-eroding systems, characterized by a first phase of burst release (in first 24 hrs), followed by a phase of slower release. The duration of the secondary phase was found to be proportional to the molecular weight and monomer ratio of copolymers and also polymer-to-drug ratios. It was confirmed that Higuchi and first-order kinetics were the predominant release mechanisms than zero order kinetic. The Korsmeyer-Peppas exponent (n) ranged between 0.10 and 0.96. This value, confirmed fickian as the dominant mechanism for PLA formulations (n ≤ 0.45) and the anomalous mechanism, for PLGAs (0.45 < n < 0.90). Conclusion: The implant of PLA (I.V. 0.2) containing 20% w/w of clindamycin, was identified as the optimum formulation in providing continuous efficient in-vitro release of clindamycin for about 5 weeks

Ispitivanje stabilnosti kitozanskih nanočestica s DNA-FAP-B za gensku isporuku u epitelne stanice pluća

A successful gene delivery system requires efficiency and stability during storage. Stability studies are imperative for nanomedicines containing biotechnological products such as plasmids and targeting peptides. Chitosan-DNA-FAP-B nanoparticles are novel non-viral vectors for specific gene delivery to the lung epithelial cells. In this study, the storage stability of chitosan-DNA-FAP-B nanoparticles at –20, 5 and 24 ºC was examined. Size, zeta potential and transfection efficiency of these nanoparticles in storage were also evaluated. Stability studies showed that chitosan-DNA-FAP-B nanoparticles were stable after 1 month when stored at –20 °C and retained their initial size, zeta potential and transfection efficiency. However, their stability was not desirable at 5 and 24 ºC. Based on these results, it can be concluded that chitosan-DNA-FAP-B nanoparticles can be a promising candidate for gene delivery to lung epithelial cells with good storage stability at –20 ºC during 1 month.Dobar sustav za gensku isporuku mora biti učinkovit i stabilan prilikom skladištenja. Stoga su ispitivanja stabilnosti nužna za nonosustave s biotehnološkim produktima kao što su plazmidi i ciljni peptidi. Kitozanske nanočestice s DNA-FAP-B su novi nevirusni vektori za specifičnu gensku isporuku u epitelne stanice pluća. U radu je ispitana njihova stabilnost na –20, 5 i 24 ºC, veličina čestica, zeta potencijal i transfekcijska učinkovitost. Dobiveni rezultati pokazuju da su kitozanske nanočestice s DNA-FAP-B stabilne nakon mjesec dana skladištenja na –20 °C i da zadržavaju početnu veličinu, zeta potencijal i sposobnost transfekcije, a nisu stabilne skladištenjem na 5 i 24 ºC. Može se zaključiti da su kitozanske nanočestice s DNA-FAP-B potencijalni kandidati za gensku isporuku u epitelne stanice pluća te da su dovoljno stabilne ako se skladište mjesec dana na –20 ºC