Yancai Wang

Nanosuspensions of poorly water-soluble drugs prepared by bottom-up technologies

In recent years, nanosuspension has been considered effective in the delivery of water-soluble drugs. One of the main challenges to effective drug delivery is designing an appropriate nanosuspension preparation approach with low energy input and erosion contamination, such as the bottom-up method. This review focuses on bottom-up technologies for preparation of nanosuspensions. The features and advantages of drug nanosuspension, including bottom-up methods as well as the corresponding characterization techniques, solidification methods, and drug delivery dosage forms, are discussed in detail. Certain limitations of commercial nanosuspension products are also reviewed.

Effect of PEGylated chitosan as multifunctional stabilizer for deacetyl mycoepoxydience nanosuspension design and stability evaluation.

Here a series of multifunctional stabilizers was designed and used in a nanosuspension stability enhancement study. Methoxypolyethylene glycol (M PEG)-grafted chitosan, accompanied by space steric hindrance, an electrostatic repulsion function, and a solvation effect, is a multifunctional stabilizer. Deacetyl mycoepoxydience (DM) nanosuspension was prepared using the anti-solvent precipitation approach. The effects of the DM and the multifunctional stabilizer concentration, solvent to anti-solvent ratio, crystallization and storage temperature, and ultrasonic time on drug particle formation during the anti-solvent processing were investigated and the nanosuspension stability was studied. The nanosuspension showed dendritic-like nanostructures and a crystalline state in a morphology and crystalline state study. The optimized drug and multifunctional stabilizer concentration range were selected through the response surface optimization method. The most appropriate and stable nanosuspension could be obtained through the optimal parameters. This study demonstrated that M PEG-grafted chitosan (M PEGC) could be used as a multifunctional stabilizer to control particle size and improve nanosuspension stability.

State of the art of nanocrystals technology for delivery of poorly soluble drugs

Formulation of nanocrystals is a distinctive approach which can effectively improve the delivery of poorly water-soluble drugs, thus enticing the development of the nanocrystals technology. The characteristics of nanocrystals resulted in an exceptional drug delivery conductance, including saturation solubility, dissolution velocity, adhesiveness, and affinity. Nanocrystals were treated as versatile pharmaceuticals that could be delivered through almost all routes of administration. In the current review, oral, pulmonary, and intravenous routes of administration were presented. Also, the targeting of drug nanocrystals, as well as issues of efficacy and safety, were also discussed. Several methods were applied for nanocrystals production including top-down production strategy (media milling, high-pressure homogenization), bottom-up production strategy (antisolvent precipitation, supercritical fluid process, and precipitation by removal of solvent), and the combination approaches. Moreover, this review also described the evaluation and characterization of the drug nanocrystals and summarized the current commercial pharmaceutical products utilizing nanocrystals technology.

Safety of nanosuspensions in drug delivery

Nanosuspension technology is currently undergoing dramatic expansion in pharmaceutical science research and development. However, most of the research efforts generally focus on formulation and potential beneficial description, while the research into potential toxicological effects and implications (i.e., in vivo safety and health effects) is lacking. This review identifies some of the key factors for studying nanosuspension safety and the potential undesired effects related to nanosuspension exposure. The key factors for discussion herein include particle characterization, preparation approach, composition, and excipients of the formulation and sterilization methods. A few comments on the primary and required safety aspects of each administration route are also reviewed.

Smart nanocarrier based on PEGylated hyaluronic acid for deacetyl mycoepoxydience: High stability with enhanced bioavailability and efficiency

Deacetyl mycoepoxydience (DM) nanocrystals core were stabilized by the folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG2000-FA) as the active-targeting stabilizer and D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) as the reversion of multidrug resistance stabilizer, respectively. The DM nanocrystals was acted as the core and shelled by the polyethylene glycol-hyaluronic acid (PEG-HA). The optimal core-shell system demonstrated superior stability at 4 °C for 6 weeks by the stability study and higher dissolution velocity. Cytotoxicity in vitro and cell proliferation inhibition was evaluated by MCF-7 cells line. Furthermore, the core-shell nanocrystals revealed a concentration- and time-dependent cytotoxicity activity and enhanced the cell proliferation inhibition. Pharmacokinetic studies in rabbits showed core-shelled DM nanocrystals significantly increased AUC and t1/2 and reduced CLz compared to the DM solution for intravenous delivery. Results indicated that core-shell nanocrystals nanogel was successfully established with higher stability and the bioavailability of DM with higher safety was improved.

Functional and Modified Nanocrystals Technology for Target Drug Delivery

In the face of a large number of insoluble drugs, the development of nanocrystals is effective in destroying the limits of poorly soluble drug applications and becoming an indispensable route of drug delivery in the pharmaceutical industry. In addition, the proposed delivery goal is to provide more convenience and benefits and the number of researchers who are developing a number of advanced technologies try to use improved nano-drugs to improve the bioavailability of drug, drug dissolution velocity and solubility. Previously, more mature study has been done, for example, preparation of nanocrystals, the problems of safety, the route of administration and so on. This review systematically dwells upon several of the current nanocrystals technologies for target delivery by different modification technologies, such as magnetic nanocrystals, PEG and PEGylated chitosan modified nanocrystals, cationic nanocrystals and pluronic modified nanocrystals. Subsequently, the effects of surface charge and particle size on the drug targeted administration was analyzed. This review will provide a new insight for improving stability and controllability of the nanocrystals, and promote the nanocrystals technology development in targeting drug delivery.

Deacetyl Mycoepoxydience Nanocrystals Dispersible Tablets Formulation and In Vitro Study

A novel nanocrystal dispersible tablets was developed by apply quality by design (QbD) approach in this study. Following Deacetyl Mycoepoxydience (DM) nanosuspensions was prepared by antisolvent precipitation approach; the DM nanocrystal was solidified by freeze-drying method. Following the screening of cryoprotectants for solidification of the nanosuspensions, the physicochemical properties including re-dispersability, mean particle size (MPS), morphology and dissolution behavior of the DM nanocrystal was investigated. Experiment was designed with focus on the types and quantities of disintegrating agent during the DM nanocrystal dispersible tablets preparation. The DM nanocrystal-loaded dispersible tablets were produced using direct powder compression. Judging form the tablet disintegration time, central composite design (CCD) and response surface methodology was adopted to optimize disintegrating agent. In conclusion, the nanocrystal dispersible tablets approach was a reliable method for improving the dissolution and thereby the oral bioavailability of the DM in formulation development.

Cryoprotectant choice and analyses of freeze-drying drug suspension of nanoparticles with functional stabilisers

Abstract Freeze-drying is an effective way to improve long-term physical stability of nanosuspension in drug delivery applications. Nanosuspension also known as suspension of nanoparticles. In this study, the effect of freeze-drying with different cryoprotectants on the physicochemical characteristics of resveratrol (RSV) nanosuspension and quercetin (QUE) nanosuspension was evaluated. D-α-tocopheryl polyethylene glycol succinate (TPGS) and folate-modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA) were selected as functional stabilisers formulated nanosuspension which were prepared by anti-solvent precipitation method. RSV nanoparticle size and QUE nanoparticle size were about 210 and 110 nm, respectively. The AFM and TEM results of nanosuspension showed uniform and irregular shape particles. After freeze-drying, the optimal concentration of four cryoprotectants was determined by the particle size of re-dispersed nanoparticles. The dissolution profile of drug nanoparticle significantly showed approximately at a 6–8-fold increase dissolution rate. Moreover, TPGS and DSPE-PEG-FA stabilised RSV nanosuspension and QUE nanosuspension samples showed better effect on long-term physical stability.

Nanocrystals Technology for Transdermal Delivery of Water-Insoluble Drugs

The poor penetration and low bioavailability are the main challenges for transdermal drug delivery. Nanocrystals technology is an attractive method for water-insoluble drug transdermal delivery, as the literature demonstrated that the penetration and bioavailability of the transdermal delivered water-insoluble drugs significantly enhanced and improved by the nanocrystals technology. Currently, the nanocrystals technology has been applied in transdermal delivery of cosmeceutical and for therapy of skin diseases, such as diclofenac acid, tretinoin and rutin. This review focused on the advantages of the nanocrystals technology for transdermal delivery. The special features of nanocrystals for the transdermal delivery of poorly soluble drugs are reviewed (skin disease treatment, safety and compliance, applying to cosmeceutical). Furthermore, the factors of influencing the nanocrystals penetration and the approaches of improving nanocrystals transdermal delivery are also discussed in detail.

In vitro and in vivo evaluation of targeting tumor with folate-based amphiphilic multifunctional stabilizer for resveratrol nanosuspensions

Resveratrol (RSV) nanosuspensions, with long term stability and targeting delivery ability, were designed and demonstrated by in vitro and in vivo model. The folate modified distearoylphosphatidyl ethanolamine-polyethylene glycol (DSPE-PEG-FA), as target delivery carrier, was synthesized and confirmed by FTIR and 1H NMR. D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and DSPE-PEG-FA used as stabilizers formed two RSV nanosuspensions (RSV-NA and RSV-NB), which were prepared by anti-solvent precipitation method and optimized by central composite design-response surface model (CCD-RSM). The morphology of RSV nanosuspensions showed flake shapes and spherical shapes by SEM. And the distribution of particles was uniform by TEM and AFM. The two RSV nanosuspensions displayed an amorphous state, by XRPD and DSC determination. At room temperature, the optimum RSV nanosuspensions showed long term stability for 20days. The cell proliferation and morphology study revealed that the RSV nanosuspensions significantly enhanced the in vitro cytotoxicity against A549 cells in a dose- and time-dependent manner. The recommended safe concentration was 5μM for in vitro study. In vivo studies of the two nanosuspensions also displayed higher antitumor efficacy by reduced tumor volume and weight. Compared with the saline group, the tumor inhibition ratio of the RSV-NA was 61.53±18.36% and RSV-NB was 64.61±21.13%. The mice weight of the RSV-NA group and RSV-NB group was also maintained constant increasing. These results demonstrated that TPGS and DSPE-PEG-FA could be used as stabilizers for stable RSV nanosuspensions formulation with the potentiality for targeting delivery to human alveolar carcinoma cells with high stability and efficacy.