Nutraceutical delivery systems to improve the bioaccessibility and bioavailability of lycopene: A review.

Lycopene is a promising biological functional component with various biological activities and excellent pharmacological activities. However, its low water solubility and stability lead to low oral bioavailability, which limits its edible and medicinal research. Then, it is necessary to explore effective methods to protect lycopene from destruction and further exploit its potential benefits. The absorption of lycopene in vivo is affected by solubility, stability, isomer type, emulsifying ability, difficulty in forming micelles in vivo, and interaction with food components. Emulsions, pickering emulsions, micelles, liposomes, bigels, beasds, solid dispersions, microcapsules, nanoparticles, electrospinning and other drug delivery systems can be used as good strategies to improve the stability and bioavailability of lycopene. In this paper, the absorption process of lycopene in vivo and the factors affecting its bioavailability were discussed, and the preparation strategies for improving the stability, bioavailability, and health benefits of lycopene were reviewed, to provide some clues and references for the full utilization of lycopene in the field of health. However, there are still various unresolved mysteries regarding the metabolism of lycopene. The safety and in vivo studies of various preparations should be further explored, and the above technologies also face the challenge of industrial production.

High efficient freeze-drying technology in food industry.

Freeze-drying technology is an interdisciplinary and complex technology, combined with freezing and vacuum drying, It has become an important technology for heat-sensitive drugs and food preservation. Freeze-dried foods are classified into meat, vegetables, fruits, fungus, and micro-powders, etc. In this paper, the definition, principle, steps, advantages and disadvantages of freeze-drying are summarized, and the research progress of freeze-drying in food industry in recent years is reviewed, including the technological parameters and influencing factors.

Application of cyclodextrin in food industry.

Due to special cavity structure, cyclodextrin can form inclusion complex with a large number of compounds, which can be widely used in food industry, such as enhancing antibacterial activity, extending the storage period of food, increasing the solubility of food ingredients, removing cholesterol in food and so on. In this paper, the formation mechanism, classification and properties of cyclodextrin inclusion complex were reviewed, and the applications of cyclodextrin and its derivatives in food industry were discussed.

Spray-dried curcumin nanoemulsion: A new road to improvement of oral bioavailability of curcumin.

In this study a new soluble solid curcumin nanoemulsion powder was prepared using spray-drying technology to improve the solubility and bioavailability of curcumin. The liquid nanoemulsion consisted of curcumin, Capryol 90, Transcutol P, and Cremophor RH40. The solid nanoemulsion was prepared by spray-drying the liquid nanoemulsion in laboratory spray dryer, using lactose as solid carrier. The in vitro release from powder formulation was 97.6% within 15 min while the release from the curcumin crystalline was about 10%. An oral pharmacokinetic study was conducted in rats and the relative bioavailability of spray-dried curcumin powder significantly increased compared with that of curcumin crystalline. The Cmax value of solid curcumin nanoemulsion powder was 5.5-fold greater than the value of the curcumin crystalline in aqueous suspension. The absorption mechanism of the spray-dried curcumin powders was discussed. The results indicate that spray-drying in combination with nanoemulsion was a powerful methodology for improving the dissolution rate and oral bioavailability of curcumin.

Enhancement of Oral Bioavailability of Curcumin by a Novel Solid Dispersion System.

The objective of this study was to improve the solubility and bioavailability of curcumin by a new curcumin dripping pills (Cur-DPs) formulation using melt mixing methods. The optimal formulation consisted of Polyethoxylated 40 hydrogenated castor oil (Cremophor RH40), Poloxamer 188, and Polyethylene glycol 4000 (PEG 4000). Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and Fourier-transform infrared spectroscopy (FT-IR) were used to verify the forming of Cur-DPs. All the physical characterization information proved the formation of Cur-DPs, and the results demonstrated the superiority of the dripping pills in dissolution rates. The pharmacokinetic study of Cur-DPs was performed in rats compared to the pure curcumin suspension. The oral bioavailability of poorly water-soluble curcumin was successfully improved by CUR-DPs. And the stability of prepared Cur-DP was also in a good state in 3 months. These results identified the Cur-DPs was an effective new approach for pharmaceutical application.

An overview of preparation and evaluation sustained-release injectable microspheres.

Recently, sustained-release injectable microspheres as a novel parenteral administration system have been interested on for many years, due to the excellent advantages when compared to traditional dosage forms: less administration frequency, lower adverse side effects and no need for a surgical procedure. Therefore, major progresses in the development of another successful marketed sustained-release injectable formation have been made, but most investigations are merely limited in laboratory levels; in addition, few reports focus on giving some positive guidance to launch these novel microspheres into market. This review addressed some commonly used polymers, preparation methods and sterilization processes relating to biodegradable microspheres. Moreover, the processes for measuring the sustained-release behaviour of this novel system are summarized in this report, including the methods to determine the in vitro and in vivo release behaviours and the strategies to analyse the in vitro and in vivo correlations.

Preparation, characterization and tableting of cilnidipine solid dispersions.

Solid dispersion technique has been developed many years for improving solubility of water-insoluble drugs, aiming to achieve a better oral bioavailability. However, this technique exhibits many inconveniences when used for large-scale tableting procedures. The objective of current research work was to develop cilnidipine solid dispersions (SDs) to improve the dissolution behaviors of this water-insoluble drug. Moreover, an innovative granulation method was designed to simplify the traditional tableting technology used in solid dispersion technique. Three different kinds of polymers, polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and poloxamer, were used as carriers to prepare solid dispersions. The interactions in the solid state were characterized by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and FT-IR spectroscopy. The designed granulation method was employed to prepare solid dispersion tablets and the formulation was optimized through investigating the dissolution behaviors. The results indicated PEG solid dispersion showed the best effect both on physical characterizations and dissolution studies. Furthermore, all type of solid dispersions significantly improved the dissolution rates when compared to pure drug and its corresponding physical mixture (PM). The solid dispersion tablets prepared in simplified tableting method exhibited better operability, stability and dissolution behavior than the tablets prepared in traditional ways, which brought more opportunities to solid dispersion technique for industrial production.

Development and characterization of gastro-floating sustained-release capsule with improved bioavailability of levodopa.

In this study, a new gastro-floating sustained-release capsule (GFC) with levodopa (LD) and benserazide hydrochloride (BH) was successfully developed. GFCs were prepared by filling the LD and BH granules into hard capsules and coated with cellulose acetate (CA) solution as a controlled-release layer. The effects of formulation factors on the release of GFCs were conducted. The AUC0~24 (µg h/mL) of LD were 69.31 ± 3.61 (µg h/mL) and 28.87 ± 2.58 (µg h/mL) and the Cmax were 7.84 ± 0.34 (µg/mL) and 9.21 ± 1.04 (µg/mL) in the GFCs and commercial tablets respectively. The relative bioavailability of LD was 267.55 ± 34.54%. Compared with commercial tablets, the pharmacokinetic study indicated that the developed GFCs provided a better sustained-release effect and higher bioavailability than commercial tablets.

Recent technological strategies for enhancing the stability of lycopene in processing and production.

Lycopene, a popular antioxidant, exists abundantly in nature in all-E form, but the Z-lycopene has better solubility and absorption characteristics. Lycopene is labile to light, thermal and oxygen. Emerging technological approaches are developed to improve the stability of lycopene during production and processing. This review presents the degradation mechanism of lycopene. A comprehensive evaluation has made by comparing the advantages and disadvantages of different extraction and isomerization methods. Encapsulation of lycopene in different delivery systems can further improve its stability. The process and formulation influence factors, as well as the advantages and disadvantages of lycopene encapsulation delivery systems are summarized. In the future, it is necessary to scientifically design low-cost and high-efficiency lycopene production methods.The stable and high bioavailable lycopene encapsulation systems need to be designed. Further study on the chemical stability mechanism of lycopene, the toxicity of biological materials, the safety of lycopene preparations also need to be evaluated.

Applications and prospects of intra-articular drug delivery system in arthritis therapeutics.

Arthritis is a kind of chronic disease that affects joints and muscles with the symptoms of joint pain, inflammation and limited movement of joints. Among various clinical therapies, drug therapy has been extensively applied because of its accessibility, safety and effectiveness. In recent years, the intra-articular injection has dramatic therapeutic effects in treating arthritis with high patient compliance and low side effects. In this review, we will introduce pathology of arthritis, along with the accessible treatment and diagnosis methods, then we will summarize major advances of current hopeful intra-articular delivery systems such as microspheres, hydrogels, nanoparticles and liposomes. At last, some safety assessments in the preclinical work and the main challenges for the further development of intra-articular treatment were also discussed.

Novel microporous resin-based polymer device for sustained glipizide release: Production, characterization and pharmacokinetic study.

The objective of this study was to explore an innovative sustained release technology and design a new microporous resin-based polymer device (RPD) for controlled release of glipizide (GZ). Photocurable resin was applied to prepare the resin layer to control GZ release. The impact of formulation parameters consisting of the type and amount of pore formers and pH modifiers, photocurable curing time as well as the weight of resin layer on GZ release were examined. The GZ-RPD was fabricated applying 24 mg of resin layer with PEG400 (100 % of the resin weight) as pore former and 10 mg of Na2CO3 as pH modifier. Scanning electron microscopy (SEM) demonstrated resin particles presenting a porous structure constituted the resin layer. The GZ-RPD possessed prolonged Tmax and reduced Cmax relative to commercial tablets. The relative bioavailability of the RPDs as well as commercial tablets was 93.65 % since the AUC0-24 h were 6111.05 ± 238.89 ng·h/mL and 6525.09 ± 760.59 ng h/mL, respectively. The release mechanism of the GZ-RPD was discussed. This paper provided an innovative concept to produce controlled GZ release oral formulation fabricated by photocurable resin, which demonstrated both excellent in vitro release and in vivo pharmacokinetics.

Increase of therapeutic activity of doxorubicin by long circulating liposomes in combination with curcumin.

In this study, doxorubicin (DOX)-loaded long circulating liposomes combined with curcumin (CUR) (DOX-CUR-LCLs) were successfully prepared as a novel formulation for cancer treatment. The particle size and distribution, zeta potential, drug loading capacity, and entrapment efficiency (EE) of the preparation were characterized. The in vitro anti-tumor activities of DOX-CUR-LCLs and DOX-LCLs against A549 cells were then evaluated and compared with that of free DOX. Cytotoxicity evaluation showed that DOX-CUR-LCLs had a significantly higher antitumor activity than other DOX preparations. These results suggest that novel DOX-CUR-LCLs, combination of DOX and CUR administered in long-circulating liposomes, could improve antitumor activity.

Nanoemulsion-based delivery approaches for nutraceuticals: fabrication, application, characterization, biological fate, potential toxicity and future trends.

In the modern food industry, people are paying more and more attention to the use of edible nanoemulsions to encapsulate, protect and deliver lipophilic functional ingredients, such as volatile additives, polyphenols, aromas, pigments, proteins, vitamins, oil-soluble flavors, preservatives, etc., which are the current global needs. Nanoemulsions are constructed with droplets of nano range size and they offer many potential advantages over conventional emulsions including the delivery of both hydrophilic and hydrophobic compounds, higher stability, better antibacterial properties, good taste experience, higher affinity, longer shelf-life and improvement of the bioavailability of components. Moreover, they are highly capable of improving the wettability and/or solubility of poorly water-soluble compounds, which may result in better pharmacokinetic and pharmacodynamic properties of nutraceutical compounds. On the other hand, oral nanoemulsions also have certain risks, such as their ability to change the biological fate of biologically active ingredients in the gastrointestinal tract and the potential toxicity of certain ingredients used in their production. This review article summarizes the manufacturing, application, characterization, biological fate, potential toxicity, and future challenges and trends of nanoemulsions, and focuses on nanoemulsion-based nutraceutical delivery approaches suitable for the food industry.

Microfluidic Assembly: An Innovative Tool for the Encapsulation, Protection, and Controlled Release of Nutraceuticals.

Nutraceuticals have been gradually accepted as food ingredients that can offer health benefits and provide protection against several diseases. It is widely accepted due to potential nutritional benefits, safety, and therapeutic effects. Most nutraceuticals are vulnerable to the changes in the external environment, which leads to poor physical and chemical stability and absorption. Several researchers have designed various encapsulation technologies to promote the use of nutraceuticals. Microfluidic technology is an emerging approach which can be used for nutraceutical delivery with precise control. The delivery systems using microfluidic technology have obtained much interest in recent years. In this review article, we have summarized the recently introduced nutraceutical delivery platforms including emulsions, liposomes, microspheres, microgels, and polymer nanoparticles based on microfluidic techniques. Emphasis has been made to discuss the advantages, preparations, characterizations, and applications of nutraceutical delivery systems. Finally, the challenges, several up-scaling methods, and future expectations are discussed.

Synthesis and characterization of osmotic pump capsules containing polyoxyethylene and pH modifier to control the release of nifedipine.

The aim of this study was to formulate osmotic pump capsules (OPCs) to control the release of nifedipine (NP). NP solid dispersion was prepared by solvent evaporation method. The prepared mixture of NP solid dispersion and various excipients were filled into the commercial HPMC hard capsule shells and then coated with cellulose acetate (CA) solution to form NP-OPC. The CA coating solution consisted of CA as semi-permeable membrane, and Poloxamer 188 as pore formers. The impact of addition agents, citric acid and pore formers on in vitro drug release were investigated. Furthermore, the study has highlighted the impact of paddle speed and the pH value of release media, on the release and compared the release with the commercial controlled release tablets. The in vitro drug release study indicated that drug release could reach 95% in 24 h with optimal formulation, and interestingly model fitting showed that the drug release behavior was closely followed to zero-order release kinetics. The pharmacokinetic studies were performed in rabbits with commercial controlled release tablets as reference, both preparations showed a sustained release effect. Compared with traditional preparation methods of OPCs, the new preparation process was simplified without the operation of laser drilling and the sealing process of capsule body and cap, which improved the feasibility of industrial production.

Preparation and characterization of solid lipid nanoparticles loaded with epirubicin for pulmonary delivery.

In this study, epirubicin (EPI)-loaded solid lipid nanoparticles (EPI-SLNs) were successfully prepared as an inhalable formulation for treatment of lung cancer. The physicochemical properties and in vitro pulmonary deposition of EPI-SLNs was studied. Pharmacokinetics were studied in rats by inhalation administration of EPI-SLNs and EPI-solutions respectively, the concentrations of EPI in blood and lungs were determined. Cytotoxicity was determined in A549 alveolar epithelial cells and found to be not toxic in blank SLNs and higher cytotoxicity of EPI-SLNs was found compared with that of EPI solution. In vitro deposition study suggested that SLNs remained stable during nebulization with improved respirable fraction (RF) compared to EPI-solutions. In vivo pharmacokinetic study showed that the drug concentration achieved by inhalation of EPI-SLNs was much higher than the drug concentration in plasma. Furthermore the drug concentration in lungs after inhalation of EPI-SLNs was much higher than that after administration of epirubicin solution. These findings suggest that EPI-SLNs could be used as an inhalable delivery system for treatment of lung cancer.

Improvement of digoxin oral absorption in rabbits by incorporation into solid lipid nanoparticles.

In this study, digoxin (DG)-loaded solid lipid nanoparticles (DG-SLNs) were successfully prepared by an ultrasonic and high pressure homogenization method. The particle size and distribution, drug loading capacity, drug entrapment efficiency (EE %), zeta potential, and long-term physical stability of the SLNs were characterized in detail. A pharmacokinetic study was conducted in rabbits after oral administration of 0.25 mg DG in different SLNs and it was found that the relative bioavailability of DG in the SLNs was significantly increased compared with that of a DG solution. The addition of CMC-Na in SLNs also markedly increased the oral absorption of DG. These results indicate that DG absorption is enhanced significantly by employing SLN formulations and SLNs are a potential as an oral delivery carrier for poorly water soluble drugs.

Preparation of rosiglitazone maleate sustained-release floating microspheres for improved bioavailability.

The object of this study was to prepare rosiglitazone maleate (RM) sustained-release floating microspheres and investigate their pharmacokinetics. RM microspheres were prepared with ethyl cellulose (EC) and octadecyl alcohol as the carrier materials by an emulsion-solvent diffusion method, and the properties of morphology in vitro floating capability, drug loading (DL), entrapment efficiency (EE), in vitro release and in vivo pharmacokinetics were investigated. The prepared microspheres had a completely spherical shape. The percentage of microspheres floating after 12 h was (91.45 +/- 1.62)%, and the DL and EE were (9.31 +/- 0.31)% and (89.55 +/- 1.65)% respectively. Pharmacokinetic studies demonstrated that the RM floating microspheres were superior to commercial tablets in terms of the decrease in peak plasma concentration and maintenance of RM concentration in plasma. The area under the curve of plasma concentration-time (AUC) of the floating microspheres was equivalent to that of reference tablets. The results showed that floating microspheres are a feasible approach for the sustained-release preparation of drugs which have limited absorption sites in the upper small intestine.

Preparation and enhanced oral bioavailability of cryptotanshinone-loaded solid lipid nanoparticles.

In this study, solid lipid nanoparticles (SLNs) were successfully prepared by an ultrasonic and high-pressure homogenization method to improve the oral bioavailability of the poorly water-soluble drug cryptotanshinone (CTS). The particle size and distribution, drug loading capacity, drug entrapment efficiency, zeta potential, and long-term physical stability of the SLNs were characterized in detail. A pharmacokinetic study was conducted in rats after oral administration of CTS in different SLNs, and it was found that the relative bioavailability of CTS in the SLNs was significantly increased compared with that of a CTS-suspension. The incorporation of CTS in SLNs also markedly changes the metabolism behavior of CTS to tanshinone IIA. These results indicate that CTS absorption is enhanced significantly by employing SLN formulations, and SLNs represent a powerful approach for improving the oral absorption of poorly soluble drugs.

Dental resin as controlled release layer for the development of an innovative long-acting intra-oral delivery system.

The objective of the present study was to develop a novel long-acting intra-oral delivery system (LIDS) to overcome the frequent administration by the nonparenteral route with Huperzine A (HupA) as a model drug. HupA-LIDS was prepared using a magnetic drug delivery with dental resin as release controlling layer for long-term release of HupA. The factors that influenced the drug release comprised of the type and amount of pore formers, the speed of shaker, resin layer weight and drug loading. These factors were evaluated and optimized. The in-vitro release studies showed that the system was able to deliver HupA in an approximately zero-order kinetic. The SEM study showed that the multiple orifices on the surface of a resin layer formed due to presence of pore formers, which contributed to the HupA release. The pharmacokinetic study in rabbits demonstrated the HupA-LIDS could be released in vivo for more than 8 days with prolonged Tmax and significantly reduced Cmax in comparison with commercial tablets. This study provided some pioneering ideas for developing intra-oral extended release drug delivery system using dental resin as release controlling materials. The optimized HupA-LIDS can make excellent sustained release and have the potential for the long-acting product in the therapy of Alzheimer's disease.