Solid-state encapsulation of Ag and sulfadiazine on zeolite Y carrier

Hypothesis: A new simplified procedure for encapsulation of antibacterial silver nanoparticles by Solid-state Ion Exchange (SSIE) procedure over zeolite Y, followed by deposition of sulfadiazine (SD) by dry mixing was examined for the preparation of topical antibacterial formulations. The ion-exchange and adsorptive properties of the zeolite matrix were utilized for the bactericidal Ag deposition and loading of antibiotic sulfadiazine. Experiments: Assessment of the encapsulation efficiency of both active components loaded by solid and liquid deposition methods was made by X-ray diffraction, TEM, FT-IR spectroscopy and thermogravimetric analysis (TGA). SD release kinetics was also determined. Findings: Sustained delivery of sulfadiazine has been observed from the Ag-modified zeolites compared to the parent HY material. It was found that if SD was loaded in solution, part of the zeolite silver ions was released and interacted with SD, forming AgSD. By solid-state SD deposition, the reaction between the drug and the silver was restricted within the limits of inter-atomic interaction, and total but prolonged drug release occurred. © 2015 Published by Elsevier Inc

Silver- and sulfadiazine-loaded nanostructured silica materials as potential replacement of silver sulfadiazine

Silver sulfadiazine (AgSD) is the leading topical antibacterial agent for the treatment of burn wound infections. Antibacterial effect of AgSD is limited by its poor aqueous solubility, and antibacterial activity develops only by decomposition of AgSD to silver ions and sulfadiazine. In this study, it is for the first time that application of silver-modified nanoporous silica carriers (MCM-41 or SBA-15) loaded with sulfadiazine (SD), instead of silver sulfadiazine, overcoming the abovementioned disadvantages has been demonstrated. By direct or post synthesis methods, 5–15 nm sized silver nanoparticles can be stabilized in the channels or on the outer surface of nanoporous silica supports; moreover, the empty channels can be loaded by SD molecules. The SD-loaded, silver-modified materials show sustained release properties and similar or even better antimicrobial properties than AgSD. Adsorption of AgSD on nanoporous silica particles significantly improves its water solubility

Preparation of resveratrol-loaded nanoporous silica materials with different structures

Solid, nanoporous silica-based spherical mesoporous MCM-41 and KIL-2 with interparticle mesoporosity as well as nanosized zeolite BEA materials differing in morphology and pore size distribution, were used as carriers for the preparation of resveratrol-loaded delivery systems. Two preparation methods have been applied: (i) loading by mixing of resveratrol and mesoporous carrier in solid state and (ii) deposition in ethanol solution. The parent and the resveratrol loaded carriers were characterized by XRD, TEM, N2 physisorption, thermal analysis, and FT-IR spectroscopy. The influence of the support structure on the adsorption capacity and the release kinetics of this poorly soluble compound were investigated. Our results indicated that the chosen nanoporous silica supports are suitable for stabilization of trans-resveratrol and reveal controlled release and ability to protect the supported compound against degradation regardless of loading method. The solid-state dry mixing appears very effective for preparation of drug formulations composed of poorly soluble compound

New method for preparation of delivery systems of poorly soluble drugs on the basis of functionalized mesoporous MCM-41 nanoparticles

MCM-41 silica with spherical morphology and small particle sizes (100 nm) was synthesized and modified by post-synthesis method with amino and/or carboxylic groups. Solid state reaction was applied for the first time for loading of poorly soluble drug mesalazine (5-aminosalicylic acid – 5-ASA). Thenon-loaded and drug loaded mesoporous silicas were characterized by XRD, TEM, N2 physisorption, elemental analysis, thermal analysis, FT-IR and solid state NMR spectroscopy. Quantum-chemical calculations were used to predict the interactions between the drug molecule and the functional groups of the carrier. The nanoparticles were post-coated with sodium alginate and the coating modified the rate of mesalazine release from MCM-41NH2 and MCM-41NH2COOH particles. Cytotoxic evaluation on colon adenocarcinoma cell line revealed that the alginate coating reduced cytotoxicity of mesalazine loaded in the post-coated particles compared to the pure mesalazine. The functionalized, polymer coated mesoporous systems are suitable oral drug delivery systems providing an opportunity to modify drug release

Functionalized mesoporous silica nanoparticles for oral delivery of budesonide

Non-functionalized and amino-functionalized mesoporous silica nanoparticle were loaded with anti-inflammatory drug budesonide and additionally post-coated with bioadhesive polymer (carbopol). TEM images showed spherical shape of the nanoparticles and slightly higher polydispersity after coating with carbopol. Nitrogen physisorption and thermogravimetic analysis revealed that more efficient loading and incorporation into the pores of nanoparticles was achieved with the amino-functionalized silica carrier. Infrared spectra indicated that the post-coating of these nanoparticles with carbopol led to the formation of bond between amino groups of the functionalized carrier and carboxyl groups of carbopol. The combination of amino-functionalization of the carrier with the post-coating of the nanoparticles sustained budesonide release. Further, an in vitro model of inflammatory bowel disease showed that the cytoprotective effect of budesonide loaded in the post-coated silica nanoparticles on damaged HT-29 cells was more pronounced compared to the cytoprotection obtained with pure budesonide

Stabilized micelles as delivery vehicles for paclitaxel

Paclitaxel is an antineoplastic drug used against a variety of tumors, but its low aqueous solubility and active removal caused by P-glycoprotein in the intestinal cells hinder its oral administration. In our study, new type of stabilized Pluronic micelles were developed and evaluated as carriers for paclitaxel delivery via oral or intravenous route. The pre-stabilized micelles were loaded with paclitaxel by simple solvent/evaporation technique achieving high encapsulation efficiency of approximately 70%. Gastrointestinal transit of the developed micelles was evaluated by oral administration of rhodamine-labeled micelles in rats. Our results showed prolonged gastrointestinal residence of the marker encapsulated into micelles, compared to a solution containing free marker. Further, the oral administration of micelles in mice showed high area under curve of micellar paclitaxel (similar to the area of i.v. Taxol®), longer mean residence time (9-times longer than i.v. Taxol®) and high distribution volume (2-fold higher than i.v. Taxol®) indicating an efficient oral absorption of paclitaxel delivered by micelles. Intravenous administration of micelles also showed a significant improvement of pharmacokinetic parameters of micellar paclitaxel vs. Taxol®, in particular higher area under curve (1.2-fold), 5-times longer mean residence time and lower clearance, indicating longer systemic circulation of the micelles

Poly (ethylene oxide)-block-poly (n-butyl acrylate)-blockpoly (acrylic acid) triblock terpolymers with highly asymmetric hydrophilic blocks: synthesis and aqueous solution properties

The synthesis and aggregation behaviour in aqueous media of novel amphiphilic poly(ethylene oxide)- block-poly(n-butyl acrylate)-block-poly(acrylic acid) (PEO–PnBA–PAA) triblock terpolymers were studied. Terpolymers composed of two highly asymmetric hydrophilic PEO (113 monomer units) and PAA (10–17 units) blocks, and a longer soft hydrophobic PnBA block (163 or 223 units) were synthesized by atom transfer radical polymerisation (ATRP) of n-butyl acrylate and tert-butyl acrylate (tBA), followed by selective hydrolysis of the PtBA blocks. These terpolymers are not directly soluble in water but form defined spherical micelles by employing the dialysis method as confirmed by dynamic light scattering (DLS) and cryogenic transmission microscopy (cryo-TEM). Based on terpolymer architecture and composition, a three-layered micellar structure comprising a PnBA core, a PEO/PAA middle layer, and a PEO outer layer is suggested. The micelles do not dissociate to very low concentrations and, therefore, are promising candidates for long-circulating drug delivery systems. Further, as evidenced by high-performance liquid chromatography (HPLC), the micelles can load and release, without burst effect, the hydrophobic drug paclitaxel

Indometacin loading and in vitro release properties from novel carbopol coated spherical mesoporous silica nanoparticles

Spherical MCM-41 silica nanosized particles were synthesized and post synthesis modified by 3-aminopropyltriethoxysilane (APTES) in order to prepare amino-functionalized carrier. Both types of silica particleswere loaded with indometacin and further coated with carbopol. The preservation of morphology and pore structure of the particles was observed by XRD, TEM and N2 physisorption. FT-IR spectroscopy revealed the interaction between carboxyl groups of indometacin and the amino groups of the functionalized MCM-41. Amino-functionalization of the carrier resulted in higher degree of indometacin loading in comparison to the parent MCM-41, 39% vs. 30%, respectively. The coating of drug loaded amino-MCM-41 silica particles with carbopol significantly reduced the initial burst release of indometacin. Both silica carriers demonstrated no cytotoxicity on HL-60 (acute myeloid leukemia) and K-562 (chronic myeloid leukemia) cell lines