Polymeric Nanoparticles as Oral Delivery Systems for Encapsulation and Release of Polyphenolic Compounds: Impact on Quercetin Antioxidant Activity & Bioaccessibility

A delivery system containing polymeric (Eudragit) nanoparticles has been developed for encapsulation and controlled release of bioactive flavonoids (quercetin). Nanoparticles were fabricated using a solvent displacement method. Particle size, morphology, and charge were measured by light scattering, electron microscopy and ??-potential. Encapsulation efficiency (EE) and release profiles were determined using electrochemical methods. Molecular interactions within the particle matrix were characterized by X-ray diffraction, differential scanning calorimetry, and infrared spectroscopy. Antioxidant properties of free and encapsulated quercetin were analyzed by TBARS and fluorescence spectroscopy. Bioaccessibility of quercetin was evaluated using an in vitro digestion model. Relatively small (d????370?nm) anionic polymeric nanoparticles were formed containing quercetin in a non-crystalline form (EE????67?%). The main interaction between quercetin and Eudragit was hydrogen bonding. Encapsulated quercetin remained stable during 6?months storage and maintained its antioxidant activity. Quercetin bioaccessibility within simulated small intestinal conditions was improved by encapsulation. The knowledge obtained from this study will facilitate the rational design and fabrication of polymeric nanoparticles as oral delivery systems for encapsulation, protection, and release of bioactive compounds.     

Sustained Release of Poorly Water-Soluble Drug from Hydrophilic Polymeric Film Sandwiched Between Hydrophobic Layers

This proof-of-concept study explores the feasibility of using a drug-loaded hydrophilic polymeric layer sandwiched between two hydrophobic layers for improving film drug load while achieving sustained release of poorly water-soluble drug. Such films having total thickness in range ~?146–250 μm were prepared by slurry-based casting using hydrophilic hydroxypropyl methylcellulose (HPMC) as matrix layer containing fenofibrate (FNB) as the model drug, encased between two very thin rate-limiting layers of 10 μm each of hydrophobic poly-?-caprolactone (PCL). Film precursor slurry consisted of HPMC with plasticizer and water along with micronized FNB powders, which were dry-coated with hydrophilic silica. Characterization techniques demonstrated the presence of homogeneously dispersed crystalline FNB in films. The films are very thin and hence two-dimensional; hence, average drug load per unit area in range ~?5 to ~?9 mg/cm² could be achieved by altering the thickness of the drug matrix layer. Drug amount and drug content uniformity were measured through assay of ten circular samples ~?0.712 cm² in area punched out using a circular-shaped punch tool. Drug release rate was investigated using USP IV flow-through cell and surface dissolution imaging system. Thinner films followed Fickian diffusion, and thicker films followed non-Fickian anomalous diffusion. Overall, the application of middle layer thickness could be used as a tool to manipulate drug load without the need for altering its formulation or precursor preparation by changing its thickness, hence achieving relatively high drug loading yet having sustained release of drug.     

Development and Characterization of Lyophilized Diazepam-Loaded Polymeric Micelles

Polymeric micelles were studied as delivery carriers of diazepam, a practically insoluble drug in water, for rectal administration. The diazepam-loaded polymeric micelles were developed by using poloxamer 407 (P407), poloxamer 188, and d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS). Among the used polymers, TPGS resulted in polymeric micelles with good characteristics for encapsulation of diazepam which had the small particle size of 8–12 nm and narrow size distribution (PI 0.053–0.275). Additionally, 7.5% w/v of TPGS could entirely entrap the desired concentration of diazepam (5 mg/mL). To improve the physical stability upon lyophilization, an addition of P407 of 1% w/v prevented aggregation, increased physical stability, and maintained chemical stability of the lyophilized powders of diazepam-loaded polymeric micelles for 3 months storage at 4°C. The rate and amount of diazepam release from TPGS polymeric micelles mainly depended on the concentration of TPGS. The release data were fitted to Higuchi''s model suggesting that the drug release mechanism was controlled by Fickian diffusion. In conclusion, 10% w/v TPGS and 1% w/v P407 were the optimum formulation of lyophilized diazepam-loaded polymeric micelles.Key words: diazepam, lyophilization, poloxamer 407, polymeric micelles, d-α-tocopheryl poly(ethylene glycol) 1000 succinate (TPGS)     

Lyophilized Sustained Release Mucoadhesive Chitosan Sponges for Buccal Buspirone Hydrochloride Delivery: Formulation and In Vitro Evaluation

This work aims to prepare sustained release buccal mucoadhesive lyophilized chitosan sponges of buspirone hydrochloride (BH) to improve its systemic bioavailability. Chitosan sponges were prepared using simple casting/freeze-drying technique according to 3² factorial design where chitosan grade was set at three levels (low, medium, and high molecular weight), and concentration of chitosan solution at three levels (0.5, 1, and 2%). Mucoadhesion force, ex vivo mucoadhesion time, percent BH released after 8 h (Q8h), and time for release of 50% BH (T_50%) were chosen as dependent variables. Additional BH cup and core buccal chitosan sponge were prepared to achieve uni-directional BH release toward the buccal mucosa. Sponges were evaluated in terms of drug content, surface pH, scanning electron microscopy, swelling index, mucoadhesion strength, ex vivo mucoadhesion time, and in vitro drug release. Cup and core sponge (HCH 0.5E) were able to adhere to the buccal mucosa for 8 h. It showed Q8h of 68.89% and exhibited a uni-directional drug release profile following Higuchi diffusion model.KEY WORDS: buspirone HCL, casting/freeze-drying technique, chitosan, cup and core sponge, mucoadhesive buccal sponges     

Sugar End-Capped Poly-d,l-lactides as Excipients in Oral Sustained Release Tablets

Sugar end-capped poly-d,l-lactide (SPDLA) polymers were investigated as a potential release controlling excipient in oral sustained release matrix tablets. The SPDLA polymers were obtained by a catalytic ring-opening polymerization technique using methyl α-d-gluco-pyranoside as a multifunctional initiator in the polymerization. Polymers of different molecular weights were synthesized by varying molar ratios of monomer/catalyst. The matrix tablets were prepared by direct compression technique from the binary mixtures of SPDLA and microcrystalline cellulose, and theophylline was used as a model drug. The tablet matrices showed in vitro reproducible drug release profiles with a zero-order or diffusion-based kinetic depending on the SPDLA polymer grade used. Further release from the tablet matrices was dependent on the molecular weight of the SPDLA polymer applied. The drug release was the fastest with the lowest molecular weight SPDLA grade, and the drug release followed zero-order rate. With the higher molecular weight SPDLAs, more prolonged dissolution profiles for the matrix tablets (up to 8–10 h) were obtained. Furthermore, the prolonged drug release was independent of the pH of the dissolution media. In conclusion, SPDLAs are a novel type of drug carrier polymers applicable in oral controlled drug delivery systems.     

Plant Extract Synthesized PLA Nanoparticles for Controlled and Sustained Release of Quercetin: A Green Approach

Background

Green synthesis of metallic nanoparticles (NPs) has been extensively carried out by using plant extracts (PEs) which have property of stabilizers/ emulsifiers. To our knowledge, there is no comprehensive study on applying a green approach using PEs for fabrication of biodegradable PLA NPs. Conventional methods rely on molecules like polyvinyl alcohol, polyethylene glycol, D-alpha-tocopheryl poly(ethylene glycol 1000) succinate as stabilizers/emulsifiers for the synthesis of such biodegradable NPs which are known to be toxic. So, there is urgent need to look for stabilizers which are biogenic and non-toxic. The present study investigated use of PEs as stabilizers/emulsifiers for the fabrication of stable PLA NPs. Synthesized PLA NPs through this green process were explored for controlled release of the well known antioxidant molecule quercetin.

Methodology/Principal Findings

Stable PLA NPs were synthesized using leaf extracts of medicinally important plants like Syzygium cumini (1), Bauhinia variegata (2), Cedrus deodara (3), Lonicera japonica (4) and Eleaocarpus sphaericus (5). Small and uniformly distributed NPs in the size range 70±30 nm to 143±36 nm were formed with these PEs. To explore such NPs for drugs/ small molecules delivery, we have successfully encapsulated quercetin a lipophilic molecule on a most uniformly distributed PLA-4 NPs synthesized using Lonicera japonica leaf extract. Quercetin loaded PLA-4 NPs were observed for slow and sustained release of quercetin molecule.

Conclusions

This green approach based on PEs mediated synthesis of stable PLA NPs pave the way for encapsulating drug/small molecules, nutraceuticals and other bioactive ingredients for safer cellular uptake, biodistribution and targeted delivery. Hence, such PEs synthesized PLA NPs would be useful to enhance the therapeutic efficacy of encapsulated small molecules/drugs. Furthermore, different types of plants can be explored for the synthesis of PLA as well as other polymeric NPs of smaller size.     

Paliperidone-Loaded Nanolipomer System for Sustained Delivery and Enhanced Intestinal Permeation: Superiority to Polymeric and Solid Lipid Nanoparticles

Paliperidone (PPD) is the most recent second-generation atypical antipsychotic approved for the treatment of schizophrenia. An immediate release dose causes extrapyramidal side effects. In this work, a novel nanolipomer carrier system for PPD with enhanced intestinal permeability and sustained release properties has been developed and optimized. PPD was successfully encapsulated into a lipomer consisting of a specific combination of biocompatible materials including poly-ε-caprolactone as a polymeric core, Lipoid S75, and Gelucire® 50/13 as a lipid shell and polyvinyl alcohol as a stabilizing agent. The lipomer system was characterized by dynamic light scattering, TEM, DSC, and FTIR. An optimized lipomer formulation possessed a particle size of 168 nm, PDI of 0.2, zeta potential of ?23 mV and an encapsulation efficiency of 87.27%?±?0.098. Stability in simulated gastrointestinal fluids investigated in terms of particle size, zeta potential, and encapsulation efficiency measurements ensured the integrity of the nanoparticles upon oral administration. PPD-loaded nanolipomers demonstrated a superior sustained release behavior up to 24 h and better ex vivo intestinal permeation for PPD compared to the corresponding polymeric and solid lipid nanoparticles and drug suspension. The in vitro hemocompatibility test on red blood cells revealed no hemolytic effect of PPD-loaded lipomers which reflects its safety. The elaborated nanohybrid carrier system represents a promising candidate for enhancing the absorption of PPD providing a 2.6-fold increase in the intestinal permeation flux compared to the drug suspension while maintaining a sustained release behavior. It is a convenient alternative to the commercially available dosage form of PPD.     

Bioactive Polymeric Nanoparticles for Periodontal Therapy

Aimsto design calcium and zinc-loaded bioactive and cytocompatible nanoparticles for the treatment of periodontal disease.MethodsPolymP-nActive nanoparticles were zinc or calcium loaded. Biomimetic calcium phosphate precipitation on polymeric particles was assessed after 7 days immersion in simulated body fluid, by scanning electron microscopy attached to an energy dispersive analysis system. Amorphous mineral deposition was probed by X-ray diffraction. Cell viability analysis was performed using oral mucosa fibroblasts by: 1) quantifying the liberated deoxyribonucleic acid from dead cells, 2) detecting the amount of lactate dehydrogenase enzyme released by cells with damaged membranes, and 3) by examining the cytoplasmic esterase function and cell membranes integrity with a fluorescence-based method using the Live/Dead commercial kit. Data were analyzed by Kruskal-Wallis and Mann-Whitney tests.ResultsPrecipitation of calcium and phosphate on the nanoparticles surfaces was observed in calcium-loaded nanoparticles. Non-loaded nanoparticles were found to be non-toxic in all the assays, calcium and zinc-loaded particles presented a dose dependent but very low cytotoxic effect.ConclusionsThe ability of calcium-loaded nanoparticles to promote precipitation of calcium phosphate deposits, together with their observed non-toxicity may offer new strategies for periodontal disease treatment.     

Isothermal Titration Calorimetry of Chiral Polymeric Nanoparticles

Chiral polymeric nanoparticles are of prime importance, mainly due to their enantioselective potential, for many applications such as catalysis and chiral separation in chromatography. In this article we report on the preparation of chiral polymeric nanoparticles by miniemulsion polymerization. In addition, we describe the use of isothermal titration calorimetry (ITC) to measure the chiral interactions and the energetics of the adsorption of enantiomers from aqueous solutions onto chiral polymeric nanoparticles. The characterization of chirality in nano‐systems is a very challenging task; here, we demonstrate that ITC can be used to accurately determine the thermodynamic parameters associated with the chiral interactions of nanoparticles. The use of ITC to measure the energetics of chiral interactions and recognition at the surfaces of chiral nanoparticles can be applied to other nanoscale chiral systems and can provide further insight into the chiral discrimination processes of nanomaterials. Chirality 27:613–618, 2015. © 2015 Wiley Periodicals, Inc.     

Sustained Anti-inflammatory Effect of Resveratrol-Phospholipid Complex Embedded Polymeric Patch

Resveratrol-phospholipid complex (Phytosome®) (RSVP) was found better aqueous soluble and permeable than free resveratrol (RSV). RSVPs were incorporated in polymeric patch prepared by solvent casting method using Eudragit RL 100, PVP K30, and PEG 400 for application on dermal sites for sustained treating of inflammation. Prepared patches were evaluated for various physicochemical properties, surface morphology by SEM, TEM, and compatibility of patch components by FT-IR and DSC studies. Optimized formulation (F9) gave 95.79?±?3.02% drug release and 51.36% (4.28?±?0.48 mg/cm²) skin permeation after 24 h. Skin extract when examined for drug accumulation showed 38.31?±?2.42% drug content. FE-SEM images of the patch taken after drug release and skin permeation studies showed that RSVPs in polymeric patch are stable and retain their structure after 24 h long exposure to physiologic environment. Sustained anti-inflammatory effect was established in carrageenan-induced paw edema model in which test formulation gave 84.10% inhibition of inflammation at 24 h as compared to 39.58% for standard diclofenac sodium gel. The CLSM study confirmed the localization of RSVPs for a longer period, thus enabling drug targeting to the dermis for sustained effect. Skin irritation test on rabbit revealed that the patches are safe for skin application. Histological observations suggested that after exposure to the permeants, the SC integrity had not altered and no evidence of presence of inflammatory cells found. RSVP (Phytosome®) containing patches abled to give sustained therapeutic effect that may be useful in treating acute and chronic inflammation.     

Trehalose Maintains Bioactivity and Promotes Sustained Release of BMP-2 from Lyophilized CDHA Scaffolds for Enhanced Osteogenesis In Vitro and In Vivo

Calcium phosphate (Ca-P) scaffolds have been widely employed as a supportive matrix and delivery system for bone tissue engineering. Previous studies using osteoinductive growth factors loaded Ca-P scaffolds via passive adsorption often experience issues associated with easy inactivation and uncontrolled release. In present study, a new delivery system was fabricated using bone morphogenetic protein-2 (BMP-2) loaded calcium-deficient hydroxyapatite (CDHA) scaffold by lyophilization with addition of trehalose. The in vitro osteogenesis effects of this formulation were compared with lyophilized BMP-2/CDHA construct without trehalose and absorbed BMP-2/CDHA constructs with or without trehalose. The release characteristics and alkaline phosphatase (ALP) activity analyses showed that addition of trehalose could sufficiently protect BMP-2 bioactivity during lyophilization and achieve sustained BMP-2 release from lyophilized CDHA construct in vitro and in vivo. However, absorbed BMP-2/CDHA constructs with or without trehalose showed similar BMP-2 bioactivity and presented a burst release. Quantitative real-time PCR (RT-qPCR) and enzyme-linked immunosorbent assay (ELISA) demonstrated that lyophilized BMP-2/CDHA construct with trehalose (lyo-tre-BMP-2) promoted osteogenic differentiation of bone marrow stromal cells (bMSCs) significantly and this formulation could preserve over 70% protein bioactivity after 5 weeks storage at 25°C. Micro-computed tomography, histological and fluorescent labeling analyses further demonstrated that lyo-tre-BMP-2 formulation combined with bMSCs led to the most percentage of new bone volume (38.79% ±5.32%) and area (40.71% ±7.14%) as well as the most percentage of fluorochrome stained bone area (alizarin red S: 2.64% ±0.44%, calcein: 6.08% ±1.37%) and mineral apposition rate (4.13±0.62 µm/day) in critical-sized rat cranial defects healing. Biomechanical tests also indicated the maximum stiffness (118.17±15.02 Mpa) and load of fracture (144.67±16.13 N). These results lay a potential framework for future study by using trehalose to preserve growth factor bioactivity and optimize release profile of Ca-P based delivery system for enhanced bone regeneration.     

生物可降解聚合物纳米粒给药载体

生物可降解聚合物纳米粒用于给药载体具有广阔的前景。本文综述了生物可降解聚合物纳米粒给药载体领域的最新进展 :包括纳米粒表面修饰特性、药物释放、载多肽和蛋白质等生物大分子药物传输中的潜在应用。     

Advanced Technologies for Oral Controlled Release: Cyclodextrins for Oral Controlled Release

Cyclodextrins (CDs) are used in oral pharmaceutical formulations, by means of inclusion complexes formation, with the following advantages for the drugs: (1) solubility, dissolution rate, stability, and bioavailability enhancement; (2) to modify the drug release site and/or time profile; and (3) to reduce or prevent gastrointestinal side effects and unpleasant smell or taste, to prevent drug–drug or drug–additive interactions, or even to convert oil and liquid drugs into microcrystalline or amorphous powders. A more recent trend focuses on the use of CDs as nanocarriers, a strategy that aims to design versatile delivery systems that can encapsulate drugs with better physicochemical properties for oral delivery. Thus, the aim of this work was to review the applications of the CDs and their hydrophilic derivatives on the solubility enhancement of poorly water-soluble drugs in order to increase their dissolution rate and get immediate release, as well as their ability to control (to prolong or to delay) the release of drugs from solid dosage forms, either as complexes with the hydrophilic (e.g., as osmotic pumps) and/or hydrophobic CDs. New controlled delivery systems based on nanotechnology carriers (nanoparticles and conjugates) have also been reviewed.     

Formulation of Diblock Polymeric Nanoparticles through Nanoprecipitation Technique

Nanotechnology is a relatively new branch of science that involves harnessing the unique properties of particles that are nanometers in scale (nanoparticles). Nanoparticles can be engineered in a precise fashion where their size, composition and surface chemistry can be carefully controlled. This enables unprecedented freedom to modify some of the fundamental properties of their cargo, such as solubility, diffusivity, biodistribution, release characteristics and immunogenicity. Since their inception, nanoparticles have been utilized in many areas of science and medicine, including drug delivery, imaging, and cell biology^1-4. However, it has not been fully utilized outside of "nanotechnology laboratories" due to perceived technical barrier. In this article, we describe a simple method to synthesize a polymer based nanoparticle platform that has a wide range of potential applications. The first step is to synthesize a diblock co-polymer that has both a hydrophobic domain and hydrophilic domain. Using PLGA and PEG as model polymers, we described a conjugation reaction using EDC/NHS chemistry⁵ (Fig 1). We also discuss the polymer purification process. The synthesized diblock co-polymer can self-assemble into nanoparticles in the nanoprecipitation process through hydrophobic-hydrophilic interactions.The described polymer nanoparticle is very versatile. The hydrophobic core of the nanoparticle can be utilized to carry poorly soluble drugs for drug delivery experiments6. Furthermore, the nanoparticles can overcome the problem of toxic solvents for poorly soluble molecular biology reagents, such as wortmannin, which requires a solvent like DMSO. However, DMSO can be toxic to cells and interfere with the experiment. These poorly soluble drugs and reagents can be effectively delivered using polymer nanoparticles with minimal toxicity. Polymer nanoparticles can also be loaded with fluorescent dye and utilized for intracellular trafficking studies. Lastly, these polymer nanoparticles can be conjugated to targeting ligands through surface PEG. Such targeted nanoparticles can be utilized to label specific epitopes on or in cells^7-10.Download video file.^{(41M, mov)}     

替莫唑胺局部缓释制剂的研究进展

近年来,为更有效地发挥替莫唑胺对神经胶质瘤的治疗活性,局部、缓释给药成为替莫唑胺的研究热点。本文简述了几种研发中的替莫唑胺的局部缓释新制剂,其中替莫唑胺-聚酸酐缓释微球(TMZ-pCPP：SA)由于聚酸酐表面溶蚀等特性,具有良好的缓释特性,鼠颅内植入试验显示,比口服替莫唑胺具有更好的治疗效果,因此替莫唑胺-聚酸酐缓释微球作为颅内缓释制剂具有极为光明的前景。     

Oxytocin Sustained Release Using Natural Rubber Latex Membranes

The demand for biomaterials with properties that provide sustained release of substances with pharmacological interest is constant. One candidate for applications in this area is the Natural Rubber Latex (NRL) extracted from the rubber tree Hevea brasiliensis. Recent studies indicate the NRL as a matrix for sustained release, showing promising results for biomedical applications such as: can stimulate natural angiogenesis and is capable of adhering cells on its surface, promoting the replacement and regeneration of tissue. So, the NRL is an excellent candidate to propitiate the sustained release of peptides of pharmacological interest such as oxytocin, a hormonal peptide which has the function to promote uterine muscle contractions and reduce bleeding during childbirth, and stimulate the release of breast milk. Results demonstrated that 90 μg mL^?1 (45 %) of the incorporated peptide in Natural Rubber Latex Biomedical (NRLb) functionalized membranes was released at 10 h in phosphate-buffered saline (PBS) solution. Swelling kinetics assay showed that the NRLb membranes are able to absorb over a period of 16 h up to 1.08 grams of water per grams of membrane. Scanning electron microscopy showed that the peptide was adsorbed on the surface and within NRLb membrane. Fourier transform infrared and Derivative Thermogravimetric analysis indicated that oxytocin did not interacted chemically with the membrane. Furthermore, hemolysis of erythrocytes, quantified spectrophotometrically using materials (Oxytocin, NRLb, and NRLb + Oxytocin) showed no hemolytic effects up to 100 μg mL^?1 (compounds and mixtures), indicating no detectable disturbance of the red blood cell membranes. Based on these results it was possible to conclude that the NRLb has shown effectiveness as a model in the release of peptides with pharmacological interest.     

NGF电纺纤维的体外缓释研究

目的:研究担载神经生长因子(NGF)的静电纺丝纤维的表征,考察NGF电纺纤维对于周围神经修复的效果。方法:将NGF水溶液分散于PLLA溶液,通过W/O乳液法制备静电纺丝纤维,对纤维的形态、力学性能等进行表征,Elisa方法测定NGF的体外释放动力学,Alamer Blue法检测试剂来考察纤维释放液对于PC12细胞增殖的影响。结果:NGF电纺纤维具备良好的形态和力学性质,直径为500-900 nm,纤维具备三维多孔结构。纤维的最大拉伸应力为2.50±0.41 MPa。电纺纤维中NGF在体外可有效释放9天,累积释放量接近3000 pg。细胞活性实验结果显示,第1、3、5、7天释放液的荧光强度与对照组相比有显著差异。结论:担载NGF的乳液法静电纺丝纤维有促进缺损周围神经修复的潜质。     

聚合物纳米粒在肿瘤光动力治疗中的研究进展

光动力治疗创伤小,在恶性肿瘤治疗方面的应用已经得到了临床认可。治疗过程中需要给予光敏剂,在光照下产生分子氧对肿瘤细胞产生杀伤作用。但是,大多数光敏剂缺乏对肿瘤细胞的特异性,其在肿瘤中的富集主要与细胞高代谢有关,并且在水相媒介中溶解度比较差。纳米技术应用于光动力治疗提供了一种有效地体内运输光敏剂的方式。目前,聚合物纳米粒与光动力药物传递的研究越来越多,光敏剂通过纳米粒的运输为弥补光动力治疗的不足提供了可能,这是因为纳米载体可以将治疗浓度的光敏剂运送到肿瘤细胞而不造成非靶向组织的副损伤。本文将介绍对肿瘤光动力治疗中具有特异性的聚合物纳米粒的种类及在临床中的应用情况,为肿瘤靶向治疗提供新思路。     

角蛋白载药纳米颗粒的制备及药物可控释放性能研究*

目的:以角蛋白作为药物载体材料,制备智能响应性药物递送系统,研究其药物装载和释放性能。方法:利用去溶剂法制备角蛋白纳米颗粒(KNP),以罗丹明B(RB)和姜黄素(Cur)为亲水性和疏水性模式药物,制备载药KNP。利用钨灯丝扫描电镜(SEM)、动态光散射(DLS)、傅里叶变换红外光谱(FTIR)和药物体外释放实验等对KNP的尺寸、形貌、结构、载药和释药性能进行研究。结果:成功制备出粒径均一、约为300 nm 的KNP,能够装载亲水性和疏水性药物。载药颗粒在体外释放研究中表现出pH和氧化还原双重响应性。结论:利用去溶剂法,简便、安全地制备了分散性良好且具有pH和氧化还原双重响应性释放特性的角蛋白载药纳米颗粒,为角蛋白作为智能响应型药物递送载体的研究和应用提供了参考。