| In recent years, modern techniques of drug preparation, such as nanotechnology, solid dispersion technology, liposomes, inclusion compound technology and monoclonal antibody technology, are constantly emerging and become more matured as a result of the studies of interdiscipline and advanced technology. Solid dispersion technology is a method to make drugs disperse highly in different carriers, which make SDs for different treatment aims and can increase drug efficacy. Solid dispersion formation has particular advantages, which is considered to be one of the most successful strategies to improve oral bioavailability of drugs. On the one hand, solid dispersions which involve simple operations and have good applications are not obliged to perform clinical trials since chemical structure of drug hasn’t been changed. On the other hand, it is more convenient and acceptable of solid dispersions to patients since they serve as solid oral dosage forms. Electrospinning technology which can combine nanotechnology with solid dispersion is a simple and straightforward strategy to produce nano-package medicines with a smaller dimension. In SDs, drugs can be dispersed molecularly, in microcrystals or an amorphous state in the matrix. As a result, the release profiles and bioavailability of drugs can be improved.Currently, one of the mainstreams and hot fields in pharmaceutics is the preparation of novel drug dosage forms which include oral sustained and controlled-release drug delivery system(DDS), mucosal DDS and target-oriented DDS. However, the intelligent usage of pharmaceutical excipients is significant for the application of new technology as well as the preparation of new dosage forms. The excipients can not only regulate the dissolution profiles, but also delivery drug to the targeted sites.The aim of this article is to develop electrospinning as a simple technique for the preparation of solid nanodrugs. Novel solid dispersions with excellent performance and characteristics can be prepared with the intelligent usage of functional excipients by this simple strategy. This study describes different kinds of SDs, which contain Eudragit as the filament-forming matrix, phosphatidylcholine(PC) as a surfactant, β-cyclodextrin(β-CD) as the drug carrier, non-steroidal anti-inflammatory drugs diclofenac sodium(DS) and naproxen(NAP), insoluble medicine emodin as model drugs. Firstly, different types of Eudragit were electrospun into nanofibers in optimum conditions and NAP-β-CD inclusion complex was prepared. Secondly, prepare different kinds of drug-loaded nanofibers with the compound use of active pharmaceutical ingredient(API), inclusion complex, surfactant and functional excipients- Eudragit.The primary work to electrospun Eudragit into nanofibers successfully is to select optimum electrospinning conditions. This study employed a new method to determine the appropriate electrospinning process parameters and select the suitable solvent systems. Drug-loaded nanofibers can be successfully prepared in this condition firstly. Then, structures, physical state of the components and pharmacodynamic properties of the nanofibers were characterized. Experimental results showed that drugs were highly distributed in the matrix in a molecular or amorphous form. Drugs and matrix were mixed at a molecular level which illustrated the good compatibility between them and led to the sufficient encapsulation of drug into matrix. In addition, in vitro dissolution test results from simulated gastrointestinal p H media suggested that drug release profiles of different samples had individual differences and were controlled by the properties of carriers. In a word, electrospinning technology is a simple and quick method to prepare the nanofibrous SDs which have a good compatibility and stability.Eudragit L100 and Eudragit S100 are wildly used as coating and matrix materials in oral colon targeted DDS according to their p H sensitivity. Enteric SDs, which had different drug release characteristics, were prepared by using the combined carriers of the two polymers in different proportions in this study. Different methods were conducted to analyze the performances of nanofibers. The release kinetics features and mechanisms were analyzed by fitting the dissolution profiles in p H 6.5 phosphate buffer solution(PBS) with several mathematical models. The results showed that these composite nanofibers possessed p H-dependent drug release characteristics. The higher the p H of dissolution medium, the faster the drug release rate. In p H 6.5 PBS, the in vitro drug dissolution profiles of different samples had significant difference(characteristic factor ?1>15, ?2<50), which indicated that the variational proportions of the two polymers brought about different drug release results. On the whole, the mechanisms of drug release for all the samples are the combination of matrix erosion and Fick’s diffusion. However, when the proportion of Eudragit S100 in matrix is higher than 80%, the composite nanofibers can delivery drug in a better sustained release way and can be regarded as insoluble matrix tablets.The application of NSAIDs NAP is limited due to its poor solubility and irritation of the gastrointestinal tract(GIT). In this study, NAP-β-CD inclusion complex was prepared to minimize the adverse effects and increase the permeability of NAP in GIT. The drug-loaded nanofibers were successfully prepared by using NAP-β-CD as API and Eudragit L100 as a filament-forming matrix. The physicochemical properties, in vitro drug release rate and membrane permeability were characterized. The results showed that NAP-β-CD improved the drug release profiles and membrane permeability. Moreover, drug-loaded nanofibers can protect NAP-β-CD in the low p H media and accelerate the drug release in neutral media. In addition, the drug release mechanism of NAP-β-CD was changed from Fick’s diffusion to matrix erosion when it was incorporated into nanofibers. This system can be developed as oral colon-specific DDS to protect the biomacromolecule from the damage of stomach acid.Despite extensive expertise, the traditional SDs were thermodynamically unstable, which had a tendency to change into a more stable state via the drug recrystallization. With the purpose of improving the stability of SDs during the storage, the third generation SDs was prepared by using the combined carriers of amorphous polymers-Eudragit L100 and surfactants-PC. Quality of the SDs was assessed by the phase identification, storage stability and studies on the in vitro drug dissolutio. In addition, self-assembly behavior of the composite nanofibers was discussed in order to illustrate possibility of this system to improve the oral bioavailability of the drug. Results indicated that the content of PC influenced on the properties of spinning solutions and nanofibers. The wettability and in vitro drug release rate was enhanced with the increasing ratio of PC in carriers. This system can improve the stability of SDs by inhibiting the mobility and recrystallization of NAP and solubilizing the drug in the matrix. Furthermore, this system can form self-assembly aggregation spontaneously when composite nanofibers were dissolved in a small amount of p H 7.4 PBS. In this system, drug molecule exists in different parts of the phospholipid bilayer, which will inevitably lead to less probability of effect between drug and phospholipids on the surface of gastrointestinal mucosa after oral administration. Finally, solubility and permeability of NAP was improved but the irritation of GIT reduced. The 3rd generation SDs has the potential to be developed as a novel oral solid lipid preparation.Emodin, an insoluble drug, is a kind of API of Traditional Chinese Medicine. Emodin/Eudragit L100 nanofibrous SDs were prepared successfully via electrospinning so as to increase the in vitro drug release rate. Next, they were evaluated as wound dressing. The results suggested, firstly, the in vitro drug release rate from nanofibers was increased significantly in p H 7.4 PBS. Secondly, the nanofibers showed an excellent antibacterial activity rather than obvious cytotoxicity. In addtion, when the wounds were treated by emodin/Eudragit L100 nanofibers, the fibers can absorb the fluid and form a protective layer on the wound as well as release the drug-emodin. The drug loaded nanofibers had a better wound healing effect in the early stage and repaired the wound more completely. As a consequence, emodin/Eudragit L100 nanofibers can not only be used as a short-term wound dressing, but also a template for keeping emodin in a highly dispersed state. This system may be expanded as a wound dressing with excellent performances in combination of other materials. |
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