Enhanced skin penetration of berberine from proniosome gel attenuates pain and inflammation in a mouse model of osteoarthritis.

Dermal delivery of bioactive molecules remains an attractive route of administration in osteoarthritis (OA) due to the local accumulation of drugs while avoiding their systemic side effects. In this study we propose a proniosome gel comprising non-ionic surfactants that self-assemble into de-hydrated vesicles for the delivery of the natural anti-inflammatory compound berberine. By modulating the hydrating ability of the proniosome gel, berberine can be efficiently released with minimal mechanical force.

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, Characterization and Prevention of Auto-oxidation of Amorphous Sirolimus by Encapsulation in Polymeric Films Using Hot Melt Extrusion.

Background: Sirolimus (SIR) is a macrocyclic lactone antibiotic and used therapeutically as a potent immunosuppressant for prophylaxis of kidney transplant rejection. The development of an oral dosage form is challenging because of very poor aqueous solubility (2.6µg/ml).

Orally Disintegrating Tablets Containing Melt Extruded Amorphous Solid Dispersion of Tacrolimus for Dissolution Enhancement.

In order to improve the aqueous solubility and dissolution of Tacrolimus (TAC), amorphous solid dispersions of TAC were prepared by hot melt extrusion with three hydrophilic polymers, Polyvinylpyrrolidone vinyl acetate (PVP VA64), Soluplus and Hydroxypropyl Cellulose (HPC), at a drug loading of 10% /. Molecular modeling was used to determine the miscibility of the drug with the carrier polymers by calculating the Hansen Solubility Parameters. Powder X-ray diffraction and differential scanning calorimetry (DSC) studies of powdered solid dispersions revealed the conversion of crystalline TAC to amorphous form.

Application of transglycosylated stevia and hesperidin as drug carriers to enhance biopharmaceutical properties of poorly-soluble artemisinin.

Biopharmaceutical properties of poorly water-soluble antimalarial drug, Artemisinin (ART), were improved by formulating amorphous solid dispersions with transglycosylated food additives (Hsp-G and Stevia-G) via co-spray drying. Both the formulated ART/Hsp-G and ART/Stevia-G showed superior dissolution properties with a burst release of more than 95% of drug within 5 min, whereas untreated ART dissolved only 4% in 5min. The supersaturation solubility of the formulated ART was enhanced by 2-fold as compared with untreated counterpart.

Dissolution and physicochemical stability enhancement of artemisinin and mefloquine co-formulation via nano-confinement with mesoporous SBA-15.

The objective of this study is to enhance the dissolution rate, supersaturation and physicochemical stability of combination of two poorly water-soluble anti-malarial drugs, artemisinin (ART) and mefloquine (MFQ), by encapsulating them inside mesoporous silica (SBA-15) via co-spray drying. Characteristic studies such as powder X-ray diffraction (PXRD), transmission electron microscopy (TEM) and scanning electron microscope (SEM) clearly indicate the amorphization of the crystalline drugs. ART/MQF/SBA-15 formulations show a superior dissolution enhancement with a burst release of more than 95% of drugs within 30min.

Mechanical properties and antibiotic release characteristics of poly(methyl methacrylate)-based bone cement formulated with mesoporous silica nanoparticles.

The influence of mesoporous silica nanoparticles (MSNs) loaded with antibiotics on the mechanical properties of functional poly(methyl methacrylate)-(PMMA) based bone cements is investigated. The incorporation of MSNs to the bone cements (8.15wt%) shows no detrimental effects on the biomechanical properties of the freshly solidified bone cements.

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.

Tailored Antibiotic Combination Powders for Inhaled Rotational Antibiotic Therapy.

Respiratory lung infections due to multidrug-resistant (MDR) superbugs are on a global upsurge and have very grim clinical outcomes. Their MDR profile makes therapeutic options extremely limited. Although a highly toxic antibiotic, colistin, is favored today as a "last-line" therapeutic against these hard-to-treat MDR pathogens, it is fast losing its effectiveness.

Plant polyphenols to enhance the nutritional and sensory properties of chocolates.

A relatively unexplored method to enhance the sensory and nutritional properties of chocolate is to use plant polyphenols. In this study, a low cost agricultural waste product - mangosteen (Garcinia mangostana Linn.) pericarp - was added as powder in graded amounts (1%, 2% and 3%w/w) to dark and compound chocolates during the mixing stage and evaluated.

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.

Controlled Release Inhalable Polymeric Microspheres for Treatment of Pulmonary Arterial Hypertension.

Pulmonary arterial hypertension (PAH) is a chronic ailment of the lungs, exhibiting elevated arterial pressure and vascular resistance; with a mean arterial pressure above 25 mmHg at rest and above 30 mmHg during exercise. It is associated with poor prognosis, and its prevalence is estimated to be 15 cases per one million. The current treatment options for PAH are discussed with the prostanoid class of drugs being the most effective.

Enhanced dissolution and stability of artemisinin by nano-confinement in ordered mesoporous SBA-15 particles.

Dissolution of poorly water-soluble drug, Artemisinin (ART), was enhanced by encapsulating the drug particles inside pore channels of ordered mesoporous silica, SBA-15, via co-spray drying. The drug release profiles of ART were investigated by using flow-through cell (USP IV) and in vitro dissolution tester (USP II). The co-spray-dried ART/SBA-15 samples demonstrated significantly improved dissolution rates and supersaturation compared to the untreated ART.

A novel inhaled multi-pronged attack against respiratory bacteria.

Airway mucus hypersecretion is a common clinical feature of many severe respiratory diseases, and when complicated by a recalcitrant bacterial infection, the whole treatment regimen thereby becomes more challenging and protracted. The accumulation of thickened mucus secretions in the lower airways provides a nutrient-rich breeding ground for bacteria that promotes their growth and limits the ease of effective eradication. Unfortunately, no direct-inhaled dry powder formulation to treat these respiratory mucoid infections more effectively is available commercially.

High drug load, stable, manufacturable and bioavailable fenofibrate formulations in mesoporous silica: a comparison of spray drying versus solvent impregnation methods.

Encapsulation of drugs in mesoporous silica using co-spray drying process has been recently explored as potential industrial method. However, the impact of spray drying on manufacturability, physiochemical stability and bioavailability in relation to conventional drug load processes are yet to be fully investigated. Using a 2(3) factorial design, this study aims to investigate the effect of drug-loading process (co-spray drying and solvent impregnation), mesoporous silica pore size (SBA-15, 6.

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.

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. II. Evaluation of the imidazole antifungal drug-loaded nanoparticle dispersions and their gel formulations.

This study focused on: (i) feasibility of the previously developed sucrose ester stabilized SLNs and NLCs to encapsulate different imidazole antifungal drugs and (ii) preparation and evaluation of topical gel formulations of those SLNs and NLCs. Three imidazole antifungal drugs; clotrimazole, ketoconazole and climbazole were selected for this study. The results suggested that size, size distribution and drug encapsulation efficiency depend on the drug molecule and type of nanoparticles (SLN/NLC).

Sucrose ester stabilized solid lipid nanoparticles and nanostructured lipid carriers. I. Effect of formulation variables on the physicochemical properties, drug release and stability of clotrimazole-loaded nanoparticles.

The objective of this study was to develop and evaluate solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) utilizing sucrose ester as a stabilizer/emulsifier for the controlled release of drug/active. Both SLNs and NLCs were prepared using different sugar esters to screen out the most suitable stabilizer. Clotrimazole was used as a model active/drug.

Steroid-decorated antibiotic microparticles for inhaled anti-infective therapy.

Despite advances in vaccination and antimicrobial therapy, community-acquired pneumonia (CAP) remains as a leading cause of morbidity and mortality worldwide. As the severity of CAP has been linked to the extent of inflammation in the body, adjunctive therapeutic measures aimed at modulating the immune response have therefore become increasingly attractive in recent years. In particular, for CAP patients with underlying medical conditions such as chronic obstructive pulmonary disease (COPD), a steroid-antibiotic combination will no doubt be a useful and timely therapeutic intervention.

Solid self-emulsifying drug delivery system (S-SEDDS) for improved dissolution rate of fenofibrate.

Purpose: The aim of this work was to develop and characterise S-SEDDS containing fenofibrate (FF) for dissolution enhancement.

Methods: The self-emulsifying pre-concentrate was prepared by using different proportion of Labrafac WL1349 as oily phase, Cremophor EL as surfactants and Gelucire 44/14 as co-surfactant. The prepared pre-concentrate was solidified with PEG 6000.

Novel alternatives to reduce powder retention in the dry powder inhaler during aerosolization.

Dry powder inhalers (DPIs) are used predominantly for the treatment of pulmonary diseases by delivering drugs directly into the lungs. The drug delivery efficiency is typically low and there is significant drug retention inside the DPI. An innovative 'green' initiative aimed at minimizing drug wastage via channeling the residual drug into the useful inhaled therapeutic fraction was pioneered.

Development of controlled release inhalable polymeric microspheres for treatment of pulmonary hypertension.

Pulmonary hypertension (PAH) is a condition of the lungs characterised by an elevated arterial pressure and increased vascular resistance. Existing medications have to be administered frequently, resulting in non compliance by patients. Little work has been reported to date where microspheres have been developed to control the release of drug for treatment of pulmonary hypertension.

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.