Taoran Wang

Solid lipid nanoparticles coated with cross-linked polymeric double layer for oral delivery of curcumin.

Solid lipid nanoparticles (SLNs) are regarded as promising carriers to improve the safety and effectiveness of delivery for drugs and nutrients, however, the clinic applications for oral administration are limited by their poor stability in gastrointestinal conditions. In this study, surface modification was explored to confer new physicochemical properties to SLNs and thus achieve enhanced functionalities. Novel SLNs with biopolymeric double layer (DL) coating using two natural biopolymers, i.e. caseinate (NaCas) and pectin, were prepared to encapsulate and deliver curcumin, a lipophilic bioactive compound studied as a model drug/nutrient. The DL coating was chemically cross-linked by creating covalent bonds between NaCas and pectin, using two different cross-linkers, i.e. glutaraldehyde (GA) and 1-Ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-Hydroxysuccinimide (EDC/NHS). Prior to cross-linking, the mean particle size, polydispersity index and zeta potential of DL-SLNs were 300-330nm, 0.25-0.30, -45-40mV, respectively. It was found that cross-linking with GA had a more prominent effect on particle size and polydispersity index than EDC/NHS. The cross-linking process significantly improved physicochemical properties of DL-SLNs, resulting in higher encapsulation efficiency and loading capacity, better stability and slower release profile in simulated gastrointestinal conditions. Particularly, an optimal zero-order release kinetic was observed for EDC/NHS crosslinked DL-SLNs. The electron microscopy revealed that both cross-linked DL-SLNs exhibited spherical shape with homogeneous size and smooth surface. Encapsulation of curcumin in SLNs dramatically enhanced its antioxidant activity in aqueous condition. The cross-linking process further helped spray drying of SLNs by forming homogenous powder particles. These results indicated that coating with cross-linked polymers could significantly improve the physicochemical properties of SLNs and expand their potentials as oral delivery systems for lipophilic nutrients and drugs.

Development of "all natural" layer-by-layer redispersible solid lipid nanoparticles by nano spray drying technology.

Solid lipid nanoparticles (SLNs) have gained tremendous attraction as carriers for controlled drug delivery. Despite numerous advances in the field, one long-standing historical challenge for their practical applications remains unmet: redispersibility after drying. In this work, a novel design of SLNs using a layer-by-layer (LbL) technique was developed and the formulations were optimized by surface response methodology (Box-Behnken design). To the best of our knowledge, this is the first study reporting the fabrication of SLNs from all natural ingredients in the absence of any synthetic surfactants or coatings. The SLNs were prepared by a combined solvent-diffusion and hot homogenization method, with soy lecithin as natural emulsifier (first layer), followed by the subsequent coating with sodium caseinate (second layer) and pectin (third layer), both of which are natural food biopolymers. The adsorption of pectin coating onto caseinate was reinforced by hydrophobic and electrostatic interactions induced by a pH-driven process along with thermal treatment. The innovative nano spray drying technology was further explored to obtain ultra-fine powders of SLNs. Compared to uncoated or single-layer coated SLNs powders, which showed severe aggregation after spray drying, the well-separated particles with spherical shape and smooth surface were obtained for layer-by-layer (LbL) SLNs, which were redispersible into water without variation of dimension, shape and morphology. The SLNs were characterized by Fourier transform infrared and high-performance differential scanning calorimetry for their physical properties. The LbL-coated SLNs based on all natural ingredients have promising features for future applications as drug delivery systems, overcoming the major obstacles in conventional spray drying and redispersing SLNs-based formulations.

Preparation of ultra-fine powders from polysaccharide-coated solid lipid nanoparticles and nanostructured lipid carriers by innovative nano spray drying technology

In this study, five polysaccharides were applied as natural polymeric coating materials to prepare solid lipid nanoparticles (SLN) and nanostructure lipid carriers (NLC), and then the obtained lipid colloidal particles were transformed to solid powders by the innovative nano spray drying technology. The feasibility and suitability of this new technology to generate ultra-fine lipid powder particles were evaluated and the formulation was optimized. The spray dried SLN powder exhibited the aggregated and irregular shape and dimension, but small, uniform, well-separated spherical powder particles of was obtained from NLC. The optimal formulation of NLC was prepared by a 20-30% oleic acid content with carrageenan or pectin as coating material. Therefore, nano spray drying technology has a potential application to produce uniform, spherical, and sub-microscale lipid powder particles when the formulation of lipid delivery system is appropriately designed.

Effects of different polysaccharides on the formation of egg yolk LDL complex nanogels for nutrient delivery

Five polysaccharides, pectin, carboxymethyl cellulose (CMC), gum arabic, carrageenan and alginate, were studied to form complex nanogels with egg yolk low density lipoprotein (LDL). All nanogels were smaller than 85nm with high negative zeta potential, while LDL/carrageenan and LDL/alginate nanogels exhibited more heterogeneous size distribution. Fourier transform infrared spectrum suggested that hydrogen bonds, hydrophobic and electrostatic interactions were involved to form nanogels. Overall, significant expansion of nanogels was observed after encapsulation of curcumin, being studied as a model lipophilic nutrient. Fluorescence spectra evidenced that LDL provided non-polar microenvironment for curcumin and polysaccharides played an important role in the encapsulation process. All nanogels showed sustained release of curcumin under simulated gastrointestinal conditions. Furthermore, nanoscale, smooth and spherical ultrafine dry powders of nanogels were obtained by innovative nano spray drying technology. Our study indicated that LDL/polysaccharides may serve as potential oral delivery systems for lipophilic nutrients.

Zein/caseinate/pectin complex nanoparticles: Formation and characterization

In this study, pectin was used as coating material to form zein/caseinate/pectin complex nanoparticles through pH adjustment and heating treatment for potential oral delivery applications. The preparation conditions were studied by applying heating treatment at different pHs, either the isoelectric point of zein (pH 6.2) or caseinate (pH 4.6), or consecutively at both pHs. The particulate characteristics, including particle size, polydispersity index, and zeta potential were monitored for complex nanoparticles formed under different preparation conditions. The complex nanoparticles generally exhibited particle size smaller than 200nm with narrow distribution, spherical shape, and strong negative charge. Fourier transform infrared and fluorescence spectroscopy revealed that hydrophobic interactions and hydrogen bonds were involved in the formation of complex nanoparticles, in addition to electrostatic interactions. Fresh colloidal dispersion and freeze-dried powders varied in their morphology, depending on their preparation conditions. Our results suggested that heating pH and sequence significantly affected the morphology of complex nanoparticles, and pectin coating exerted stabilization effect under simulated gastrointestinal conditions. The present study provides insight into the formation of protein/polysaccharide complex nanoparticles under different preparation conditions.

Preparation of lipid nanoparticles with high loading capacity and exceptional gastrointestinal stability for potential oral delivery applications

Exploitation of lipid nanoparticles for oral delivery of nutrients and drugs is limited by their poor stability under gastrointestinal tract and low loading capacity, unless a high concentration of synthetic surfactants is formulated. The main objective of present study is to design a series of new formulations for solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) that are suitable for potential oral delivery applications, using natural biopolymers, i.e. sodium caseinate (NaCas) as emulsifier and pectin as coating, with minimal addition of a synthetic surfactant, Tween 80. Effects of pectin coating, concentration of Tween 80, thermal treatment (80°C for 30min), as well as two chemical cross-linkers on the particulate characteristics, stability, encapsulation efficiency, controlled release and drying feasibility were comprehensively investigated. The intermolecular interactions and cross-linking reactions were studied using Fourier transform infrared spectroscopy. Tween 80 at 0.15% (w/v) together with 0.15% (w/v) NaCas was proved effective to obtain stable cross-linked pectin-coated SLN (PSLN) under 200nm with high loading capacity for curcumin, while NLC prepared under the same condition failed to pass storage stability test. The 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) cross-linked PSLN exhibited superior characteristics than glutaradehyde (GA) cross-linked PSLN, especially for the stability and controlled release under simulated gastrointestinal conditions, with curcumin studied as a model compound. The feasibility of both nano spray drying and freeze-drying technologies were both investigated to transform of colloidal lipid nanoparticles into dry powders. Our results demonstrated a novel strategy to prepare small and homogenous SLN with exceptional GI stability and high loading capacity as a potential oral delivery system.

Chemical crosslinking improves the gastrointestinal stability and enhances nutrient delivery potentials of egg yolk LDL/polysaccharide nanogels

Egg yolk low density lipoprotein (LDL)/polysaccharide nanogels are newly explored as oral delivery systems with promising encapsulation potentials. Nonetheless, the stability of nanogels against aggregation in gastrointestinal tract remains a challenge. Therefore, chemical crosslinking by 1-ethyl-3-(3-dimethylaminopropyl) and carbodiimide/N-hydroxysuccinimide (EDC/NHS) was adopted to improve the gastrointestinal stability of nanogels. Compared to original uncrosslinked nanogels, crosslinking did not change particle size, polydispersity index (PDI) and morphology, but it reduced surface charge of nanogels. The nano spray dried LDL/CMC/EDC nanogels had relatively poor surface structure with agglomerations. The FT-IR spectra confirmed the formation of new peptide bonds, which significantly improved stability of nanogels under simulated gastrointestinal conditions. Fluorescence spectra evidenced that non-polar microenvironment for curcumin embedded in nanogels was strengthened, which therefore enhanced encapsulation efficiency. Moreover, curcumin exhibited sustained release profile from crosslinked nanogels in simulated gastrointestinal fluids. Overall, our study provided a promising strategy to enhance the stability of LDL-based nanogels in digestive conditions.

Synthetic surfactant- and cross-linker-free preparation of highly stable lipid-polymer hybrid nanoparticles as potential oral delivery vehicles

The toxicity associated with concentrated synthetic surfactants and the poor stability at gastrointestinal condition are two major constraints for practical applications of solid lipid nanoparticles (SLN) as oral delivery vehicles. In this study, a synthetic surfactant-free and cross-linker-free method was developed to fabricate effective, safe, and ultra-stable lipid-polymer hybrid nanoparticles (LPN). Bovine serum albumin (BSA) and dextran varying in molecular weights were first conjugated through Maillard reaction and the conjugates were exploited to emulsify solid lipid by a solvent diffusion and sonication method. The multilayer structure was formed by self-assembly of BSA-dextran micelles to envelope solid lipid via a pH- and heating-induced facile process with simultaneous surface deposition of pectin. The efficiency of different BSA-dextran conjugates was systematically studied to prepare LPN with the smallest size, the most homogeneous distribution and the greatest stability. The molecular interactions were characterized by Fourier transform infrared and fluorescence spectroscopies. Both nano spray drying and freeze-drying methods were tested to produce spherical and uniform pectin-coated LPN powders that were able to re-assemble nanoscale structure when redispersed in water. The results demonstrated the promise of a synthetic surfactant- and cross-linker-free technique to prepare highly stable pectin-coated LPN from all natural biomaterials as potential oral delivery vehicles.

A novel and organic solvent-free preparation of solid lipid nanoparticles using natural biopolymers as emulsifier and stabilizer

In this work, a new and novel organic solvent-free and synthetic surfactant-free method was reported to fabricate stable solid lipid nanoparticles (SLNs) from stearic acid, sodium caseinate (NaCas) and pectin, as well as water. Melted stearic acid was directly emulsified into an aqueous phase containing NaCas and pectin, followed by pH adjustment and thermal treatment to induce the formation of a compact and dense polymeric coating which stabilized SLNs. The preparation procedures and formulations were comprehensively optimized. The inter- and intra-molecular interactions among three ingredients were characterized by fluorescence and Fourier transform infrared spectroscopies. The stability of as-prepared SLNs was evaluated under simulated gastrointestinal conditions, and compared with traditional SLNs prepared with organic solvents. Our results revealed that the SLNs prepared from this organic solvent-free method had superior physicochemical properties over the traditional SLNs, including smaller size and better stability. Furthermore, redispersible SLNs powders were obtained by nano spray drying, but only the SLNs prepared by organic solvent-free method had sub-micron scale, uniform and spherical morphology. The organic solvent-free preparation method was proved to be a promising approach to prepare stable and uniform SLNs for potential oral delivery applications.

Formation of redispersible polyelectrolyte complex nanoparticles from gallic acid-chitosan conjugate and gum arabic

Polyelectrolyte complex (PEC) nanoparticles between chitosan (CS) and biomacromolecules offer better physicochemical properties as delivery vehicles for nutrients than other CS-based nanoparticles. Our major objective was to fabricate PEC nanoparticles between water soluble gallic acid-chitosan conjugate (GA-CS) and gum arabic. The optimal fabrication method, physicochemical characteristics and stability were investigated. Furthermore, we also evaluated the effects of nano spray drying technology on the morphology and redispersibility of nanoparticle powders using Buchi B-90 Nano Spray Dryer. Results showed that the mass ratio between GA-CS and gum arabic and the preparation pH had significant contributions in determining the particle size and count rate of the nanoparticles, with the ratio of 3:1 and pH 5.0 being the optimal conditions that resulted in 112.2nm and 122.9kcps. The polyethylene glycol (PEG) played a vital role in forming the well-separated spray dried nanoparticles. The most homogeneous nanoparticles with the smoothest surface were obtained when the mass ratio of GA-CS and PEG was 1:0.5. In addition, the GA-CS/gum arabic spray dried nanoparticles exhibited excellent water-redispersibiliy compared to native CS/gum arabic nanoparticles. Our results demonstrated GA-CS/gum arabic nanoparticles were successfully fabricated with promising physicochemical properties and great potential for their applications in food and pharmaceutical industries.