Development and optimization of self-nanoemulsifying drug delivery systems (SNEDDS) for curcumin transdermal delivery: an anti-inflammatory exposure

The purpose of this work is to develop novel lipid-based self-nanoemulsifying drug delivery systems (SNEDDS) as carriers for transdermal delivery of curcumin. SNEDDS containing black seed oil, medium chain mono- and diglycerides and surfactants, were prepared as curcumin delivery vehicles. Their formation spontaneity, morphology, droplet size, and drug loading were evaluated. Gel preparation containing two of the SNEDDS formulations were used in the carrageenan induced paw edema to evaluate the anti-inflammatory effect. Results showed droplet size as low as 71?nm. The highest drug loading was observed with SNEDDS-F6 of ～45?mg/g. In in-vivo investigation, SNEDDS-F6 exhibited significant anti-inflammatory activities in terms of 80% reduction in paw edema when compared with positive control. The prepared SNEDDS with the elevated entrapment efficiency, good transdermal penetration ability could be a suitable candidate for effective transdermal curcumin skin delivery.     

Development and evaluation of hollow mesoporous silica microspheres bearing on enhanced oral delivery of curcumin

The aim of this work is to develop curcumin-loaded hollow mesoporous silica microspheres (HMSMs@curcumin) to improve the poor oral bioavailability of curcumin. Hollow mesoporous silica microspheres (HMSMs) were synthesized in facile route using a hard template. HMSMs and HMSMs@curcumin were characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), nitrogen adsorption/desorption measurements, differential scanning calorimetry (DSC), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). In addition, to demonstrate the potential application of the HMSMs@curcumin, cytotoxicity, in vitro release behavior and in vivo pharmacokinetics of curcumin loaded in these HMSMs were investigated by using of Caco-2 cells and Sprague-Dawley (SD) rats, respectively. These mono-dispersed HMSMs exhibited high drug loading ratio and encapsulation efficiency due to the mesoporous shell and hollow core. The excellent characteristics of HMSMs such as mono-dispersed morphology, smooth surface, uniform, ordered and size-narrowing mesopores resulted in a good in vitro release profile of curcumin from HMSMs@curcumin. Moreover, an impressive improvement in the oral absorption of curcumin and prolonged systemic circulation time were achieved in the in vivo animal studies. In addition, the good biocompatibility of developed HMSMs with Caco-2 cells was confirmed based on the in vitro cytotoxicity assay. In conclusion, this system demonstrated a great potential for efficient delivery of curcumin in vitro and in vivo, suggesting a good prospect for its application in clinic for therapeutic drug delivery in future.     

PLA-PEG-PLA copolymer-based polymersomes as nanocarriers for delivery of hydrophilic and hydrophobic drugs: preparation and evaluation with atorvastatin and lisinopril

Tri-block poly(lactide)–poly(ethylene glycol)–poly(lactide) (PLA–PEG–PLA) copolymers were synthesized and used to prepare polymersomes loaded separately by the hydrophobic and hydrophilic model drugs, atorvastatin and lisinopril, respectively. The resulting nanostructures were characterized by various techniques such as FTIR, DSC, PCS and AFM. The polymersomes exhibited high encapsulation efficiencies of almost 78% and 70.8% for atorvastatin and lisinopril, respectively. Investigation on FTIR and DSC results revealed that such a high encapsulation efficiency is due to strong interaction between atorvastatin and the copolymer. The impact of drug/copolymer ratio and copolymer composition on drug-loading efficiency and drug release behavior were also studied. The results showed that in case of lisinopril, polymersomes exhibited a triphasic drug release, while for atorvastatin a biphasic release profile was obtained. Overall, the results indicated that PLA–PEG–PLA polymersomes can be considered as a promising carrier for both hydrophilic and hydrophobic drugs.     

Proton-resistant quantum dots: Stability in gastrointestinal fluids and implications for oral delivery of nanoparticle agents

Semiconductor quantum dots (QDs) have shown great promise as fluorescent probes for molecular, cellular and in vivo imaging. However, the fluorescence of traditional polymer-encapsulated QDs is often quenched by proton-induced etching in acidic environments. This is a major problem for applications of QDs in the gastrointestinal tract because the gastric (stomach) environment is strongly acidic (pH 1–2). Here we report the use of proton-resistant surface coatings to stabilize QD fluorescence under acidic conditions. Using both hyperbranched polyethylenimine (PEI) and its polyethylene glycol derivative (PEG-grafted PEI), we show that the fluorescence of core shell CdSe /CdS/ ZnS QDs is effectively protected from quenching in simulated gastric fluids. In comparison, amphiphilic lipid or polymer coatings provide no protection under similarly acidic conditions. The proton-resistant QDs are found to cause moderate membrane damage to cultured epithelial cells, but PEGylation (PEG grafting) can be used to reduce cellular toxicity and to improve nanoparticle stability.      

Freeze drying optimization of polymeric nanoparticles for ocular flurbiprofen delivery: effect of protectant agents and critical process parameters on long-term stability

Context: The stabilization of flurbiprofen loaded poly-?-caprolactone nanoparticles (FB-P?CL-NPs) for ocular delivery under accurate freeze-drying (FD) process provides the basis for a large-scale production and its commercial development.

Objective: Optimization of the FD to improve long-term stability of ocular administration’s FB-P?CL-NPs.

Methods: FB-P?CL-NPs were prepared by solvent displacement method with poloxamer 188 (P188) as stabilizer. Freezing and primary drying (PD) were studied and optimized through freeze-thawing test and FD microscopy. Design of experiments was used to accurate secondary drying (SD) conditions and components concentration. Formulations were selected according to desired physicochemical properties. Furthermore, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) were used to study interactions components.

Results: Optimized FB-P?CL-NPs, stabilized with 3.5% (w/w) P188 and protected with 8% (w/w) poly(ethylene glycol), was submitted to precooling at +10?°C for 1?h, freezing at ?50?°C for 4?h, PD at +5?°C and 0.140 mbar for 24?h and a SD at +45?°C during 10?h. These conditions showed 188.4?±?1.3?nm, 0.087?±?0.014, 85.5?±?1.4%, 0.61?±?0.12%, ?16.4?±?0.1?mV and 325?±?7 mOsm/kg of average size, polydispersity index, entrapment efficiency, residual moisture, surface charge and osmolality, respectively. It performed a long-term stability >12 months. DSC and XRD spectra confirmed adequate chemical interaction between formulation components and showed a semi-crystalline state after FD.

Conclusions: An optimal freeze dried ocular formulation was achieved. Evidently, the successful design of this promising colloidal system resulted from rational cooperation between a good formulation and the right conditions in the FD process.     

Direct assembly of preformed nanoparticles and graft copolymer for the fabrication of micrometer-thick, organized TiO2 films: high efficiency solid-state dye-sensitized solar cells

Solid-state dye-sensitized solar cell with 7.1% efficiency at 100 mW/cm(2) is reported, one of the highest observed for N719 dye. Excellent performance was achieved via a graft copolymer-templated, organized mesoporous TiO(2) film with a large surface area using spindle-shaped, preformed TiO(2) nanoparticles and solid polymer electrolyte.