Artemether-Loaded Zein Nanoparticles: An Innovative Intravenous Dosage Form for the Management of Severe Malaria.

Artemether, an artemisinin derivative, is used in the management of life-threatening severe malaria. This study aimed to develop an intravenous dosage form of artemether using nanotechnology. Artemether-loaded zein nanoparticles were prepared by modified antisolvent precipitation using sodium caseinate as a stabilizer.

Preparation of quercetin nanorod/microcrystalline cellulose formulation via fluid bed coating crystallization for dissolution enhancement.

This study reports a novel quercetin nanorod/microcrystalline cellulose (MCC) formulation prepared by fluid bed coating crystallization technique. The process comprises fluidized bed spray coating of quercetin acetone solution onto MCC particles, solvent evaporation and crystallization of quercetin nanorods on MCC surface. Depending on the quercetin solution concentration, quercetin nanorods with 100-300 nm in diameter and 1-3 µm in length were obtained.

Preparation and characterization of quercetin/dietary fiber nanoformulations.

Quercetin is well known for its beneficial health effects on the human body. However, the slow dissolution rate leading to poor bioavailability constitutes a barrier to being further developed for nutritional products. In this work, quercetin was co-precipitated with dietary fibers into a fast-dissolving nanoformulation via antisolvent precipitation, followed by spray drying.

Hot-melt extrusion microencapsulation of quercetin for taste-masking.

Besides its poor dissolution rate, the bitterness of quercetin also poses a challenge for further development. Using carnauba wax, shellac or zein as the shell-forming excipient, this work aimed to microencapsulate quercetin by hot-melt extrusion for taste-masking. In comparison with non-encapsulated quercetin, the microencapsulated powders exhibited significantly reduced dissolution in the simulated salivary pH 6.

Nanostructured material formulated acrylic bone cements with enhanced drug release.

To improve antibiotic properties, poly(methyl methacrylate) (PMMA)-based bone cements are formulated with antibiotic and nanostructured materials, such as hydroxyapatite (HAP) nanorods, carbon nanotubes (CNT) and mesoporous silica nanoparticles (MSN) as drug carriers. For nonporous HAP nanorods, the release of gentamicin (GTMC) is not obviously improved when the content of HAP is below 10%; while the high content of HAP shows detrimental to mechanical properties although the release of GTMC can be substantially increased. As a comparison, low content of hollow nanostructured CNT and MSN can enhance drug delivery efficiency.

Clay as a matrix former for spray drying of drug nanosuspensions.

Utilization of sugars (e.g. lactose, sucrose) as matrix formers for spray drying of drug nanosuspensions is associated with two drawbacks: (1) sugars are incapable of preventing agglomeration of drug nanoparticles (NPs) in the suspension state; and (2) the spray-dried sugars are usually amorphous and hygroscopic.

Scalable ionic gelation synthesis of chitosan nanoparticles for drug delivery in static mixers.

The purpose of this study is to synthesize chitosan (CS) nanoparticles (NPs) by ionic gelation with tripolyphosphate (TPP) as crossslinker in static mixers. The proposed static mixing technique showed good control over the ionic gelation process and 152-376 nm CS NPs were achieved in a continuous and scalable mode. Increasing the flow rates of CS:TPP solution streams, decreasing the CS concentration or reducing the CS:TPP solution volume ratio led to the smaller particles.

Applications of mesoporous materials as excipients for innovative drug delivery and formulation.

Due to uniquely ordered nanoporous structure and high surface area as well as large pore volume, mesoporous materials have exhibited excellent performance in both controlled drug delivery with sustained release profiles and formulation of poorly aqueoussoluble drugs with enhanced bioavailability. Compared with other bulk excipients, mesoporous materials could achieve a higher loading of active ingredients and a tunable drug release profile, as the high surface density of surface hydroxyl groups offered versatility to be functionalized. With drug molecules stored in nano sized channels, the pore openings could be modified using functional polymers or nano-valves performing as stimuli-responsive release devices and the drug release could be triggered by environmental changes or other external effects.

Solid lipid nanoparticles: continuous and potential large-scale nanoprecipitation production in static mixers.

This work aimed at developing continuous and scalable nanoprecipitation synthesis of solid lipid nanoparticles (SLN) by mixing lipids acetonic solution with water using static mixers. The developed platform exhibited good control over the nanoprecipitation process and enabled the production of SLN below 200 nm at a throughput of 37.5-150 g/h (for 25 mg/ml lipid solution at a flow rate of 25-100 ml/min).

Controlled antisolvent precipitation of spironolactone nanoparticles by impingement mixing.

Continuous antisolvent precipitation of spironolactone nanoparticles were performed by impingement mixing in this work. In the range of Reynolds numbers (Re) 2108-6325 for the antisolvent water stream and 1771-5313 for the solvent stream, i.e.

Continuous and scalable process for water-redispersible nanoformulation of poorly aqueous soluble APIs by antisolvent precipitation and spray-drying.

This work investigates the technical feasibility of formulating water-redispersible nanocrystals of a poorly aqueous soluble drug by a continuous and scalable route. By coupling antisolvent precipitation with immediate spray-drying, fenofibrate nanoparticles were precipitated and formulated into a dry powder form containing lactose or mannitol as redispersant, hydroxylpropyl methyl cellulose (HPMC) and sodium dodecyl sulfate (SDS) as stabilizers. Field emission scanning electron microscopy (FESEM) and dynamic laser light scattering (DLLS) showed that nanosized fenofibrate were observed both upon precipitation and after the formulated powder was reconstituted in water.

DNA stretching in the nucleosome facilitates alkylation by an intercalating antitumour agent.

DNA stretching in the nucleosome core can cause dramatic structural distortions, which may influence compaction and factor recognition in chromatin. We find that the base pair unstacking arising from stretching-induced extreme minor groove kinking near the nucleosome centre creates a hot spot for intercalation and alkylation by a novel anticancer compound. This may have far reaching implications for how chromatin structure can influence binding of intercalator species and indicates potential for the development of site selective DNA-binding agents that target unique conformational features of the nucleosome.

A continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs.

Rapid and homogeneous mixing of the solvent and antisolvent is critical to achieve submicron drug particles by antisolvent precipitation technique. This work aims to develop a continuous and highly effective static mixing process for antisolvent precipitation of nanoparticles of poorly water-soluble drugs with spironolactone as a model drug. Continuous antisolvent production of drug nanoparticles was carried out with a SMV DN25 static mixer comprising 6-18 mixing elements.

Stabilized amorphous state of ibuprofen by co-spray drying with mesoporous SBA-15 to enhance dissolution properties.

A novel formulation process via co-spray drying ibuprofen (IBU) with mesoporous SBA-15 submicron particles exhibited excellence in production of stable amorphous IBU with significantly enhanced dissolution rate. With drug loading of IBU/SBA-15 ratio being 50:50 (w/w) or below, most drug molecules were entrapped inside the straight mesoporous channels via the co-spray drying and the morphology of SBA-15 submicron particles remained unchanged. IBU confined inside the mesoporous structure was in the amorphous state shown by PXRD and DSC measurements.

Preparation and characterization of spironolactone nanoparticles by antisolvent precipitation.

Due to low aqueous solubility and slow dissolution rate, spironolactone, a synthetic steroid diuretic, has a low and variable oral bioavailability. Nanoparticles were thus prepared by antisolvent precipitation in this work for accelerating dissolution of this kind of poorly water-soluble drugs. Effects of surfactant type/concentration and feed drug concentration on the precipitated particle size were evaluated.

Solubilization and preformulation of poorly water soluble and hydrolysis susceptible N-epoxymethyl-1,8-naphthalimide (ENA) compound.

N-Epoxymethyl-1,8-naphthalimide (ENA) is a novel antiproliferative drug candidate with potent anticancer and antifungal activity. It has an aqueous solubility of 0.0116mg/mL and also exhibits hydrolytic instability with a first-order hydrolysis rate of 0.

d-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) modified poly(l-lactide) (PLLA) films for localized delivery of paclitaxel.

d-alpha-Tocopheryl polyethylene glycol 1000 succinate (TPGS) was used as a novel additive to the poly(l-lactide) (PLLA) films for local drug delivery with paclitaxel as a prototype therapeutic agent. Paclitaxel-loaded PLLA/TPGS films were prepared by the solvent casting technique with dichloromethane as the solvent. Effects of TPGS component on the films' physicomechanical properties and the drug release profile were investigated.

In vitro and in vivo evaluation of methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles for small-molecule drug chemotherapy.

Methoxy polyethylene glycol-polylactide (MPEG-PLA) nanoparticles (NPs) were prepared by the nanoprecipitation method with particle size of 140+/-21nm in diameter and drug encapsulation efficiency of 87.6+/-3.1%.

Poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles prepared by high pressure homogenization for paclitaxel chemotherapy.

High pressure homogenization was employed in the current work to prepare poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles (NPs) for controlled release of paclitaxel. The prepared drug-loaded PLGA NPs were found of spherical shape with a size of 200-300 nm. The drug encapsulation efficiency ranged from 34.

Nanoparticles of poly(D,L-lactide)/methoxy poly(ethylene glycol)-poly(D,L-lactide) blends for controlled release of paclitaxel.

Paclitaxel is one of the best antineoplastic drugs found in nature in the past decades, which has excellent therapeutic effects against a wide spectrum of cancers. Because of its high hydrophobicity, Cremophor EL has to be used as adjuvant in its clinical dosage form (Taxol), which has been found to cause serious side effects. Nanoparticles of biodegradable polymers may provide an ideal solution.

Poly(d,l-lactide-co-glycolide)/montmorillonite nanoparticles for oral delivery of anticancer drugs.

This research developed a novel bioadhesive drug delivery system, poly(d,l-lactide-co-glycolide)/montmorillonite (PLGA/MMT) nanoparticles, for oral delivery of paclitaxel. Paclitaxel-loaded PLGA/MMT nanoparticles were prepared by the emulsion/solvent evaporation method. MMT was incorporated in the formulation as a matrix material component, which also plays the role of a co-emulsifier in the nanoparticle preparation process.

Methoxy poly(ethylene glycol)-poly(lactide) (MPEG-PLA) nanoparticles for controlled delivery of anticancer drugs.

Methoxy poly(ethylene glycol)-poly(lactide) copolymer (MPEG-PLA) was synthesized and used to make nanoparticles by the nanoprecipitation method for clinical administration of antineoplastic drugs. Paclitaxel was used as a prototype drug due to its excellent efficacy and commercially great success. The size and size distribution, surface morphology, surface charge and surface chemistry of the paclitaxel-loaded nanoparticles were then investigated by laser light scattering, atomic force microscopy, zeta-potential analyzer and X-ray photoelectron spectroscopy (XPS).