Liposomes/chitosan scaffold/human fibrin gel composite systems for delivering hydrophilic drugs--release behaviors of tirofiban in vitro

A new liposomes/chitosan scaffold/human fibrin gel composite system (LCSHFG), as a depot drug delivery system, was developed to deliver low-molecular weight hydrophilic drugs. An antithrombosis drug, Tirofiban, was used as a model drug. Human fibrin gels encapsulated Tirofiban loaded liposomes were formed within chitosan scaffolds to configure the LCSHFG. The in vitro release behaviors of Tirofiban from LCSHFG were studied by characterizing the constituents of LCSHFG. The results show that the release periods of Tirofiban from LCSHFG with 50 microm pores in the chitosan scaffolds are generally 20% or longer more than those with 200 microm pores. The following results were obtained for the system that comprised 50 microm pores. The release periods of Tirofiban from LCSHFG loaded with stearylamine (SA)-liposomes can sustain 20% longer and significantly less burst release (p < 0.01, n = 3) than with liposomes. The release profiles of Tirofiban from LCSHFG change markedly when 0.5 and 2.5% glutaraldehyde is used to cross-link the system. Additionally, for all liposomes, the release periods of Tirofiban from cross-linked LCSHFG with 2.5% glutaraldehyde are 40% or more longer time (e.g., 19 days) with significantly less burst release (p < 0.01, n = 3) than those of noncrosslinked LCSHFG. Notably, the bioactivity of released Tirofiban from LCSHFG that is crosslinked by 2.5% glutaraldehyde effectively inhibits adenosine diphosphate inducing platelet aggregation. The work also suggests that LCSHFG may have potential as a depot drug delivery system for low-molecular-weight hydrophilic drugs.     

Electrospun nanofibrous polymeric scaffold with targeted drug release profiles for potential application as wound dressing

We have successfully fabricated a dual drug release electrospun scaffold containing an anesthetic, lidocaine, and an antibiotic, mupirocin. Two drugs with different lipophilicities were electrospun from a poly-l-lactic acid (PLLA) solution with a dual spinneret electrospinning apparatus into a single scaffold. The release of the drugs from the scaffold showed different profiles for the two drugs. Lidocaine hydrochloride exhibited an initial burst release (80% release within an hour) followed by a plateau after the first few hours. Mupirocin exhibited only a 5% release in the first hour before experiencing a more sustained release to provide antibacterial action for over 72 h. For comparative purposes, both drugs were spun from a single spinneret and evaluated to determine their release profiles. The scaffold maintained its antibiotic activity throughout the processes of electrospinning and gas sterilization and supported cell viability. It has been reported in the literature that interactions between polymer and drug are known to govern the pattern of drug release from electrospun scaffolds. Here, it was found that the presence of the two drugs in the same polymer matrix altered the release kinetics of at least one drug. Based on the release profiles obtained, the dual spinneret technique was the preferred method of scaffold fabrication over the single spinneret technique to obtain a prototype wound healing device.     

Composite polymer-bioceramic scaffolds with drug delivery capability for bone tissue engineering

Introduction: Next-generation scaffolds for bone tissue engineering (BTE) should exhibit the appropriate combination of mechanical support and morphological guidance for cell proliferation and attachment while at the same time serving as matrices for sustained delivery of therapeutic drugs and/or biomolecular signals, such as growth factors. Drug delivery from BTE scaffolds to induce the formation of functional tissues, which may need to vary temporally and spatially, represents a versatile approach to manipulating the local environment for directing cell function and/or to treat common bone diseases or local infection. In addition, drug delivery from BTE is proposed to either increase the expression of tissue inductive factors or to block the expression of others factors that could inhibit bone tissue formation. Composite scaffolds which combine biopolymers and bioactive ceramics in mechanically competent 3D structures, including also organic–inorganic hybrids, are being widely developed for BTE, where the affinity and interaction between biomaterials and therapeutic drugs or biomolecular signals play a decisive role in controlling the release rate.

Areas covered: This review covers current developments and applications of 3D composite scaffolds for BTE which exhibit the added capability of controlled delivery of therapeutic drugs or growth factors. A summary of drugs and biomolecules incorporated in composite scaffolds and approaches developed to combine biopolymers and bioceramics in composites for drug delivery systems for BTE is presented. Special attention is given to identify the main challenges and unmet needs of current designs and technologies for developing such multifunctional 3D composite scaffolds for BTE.

Expert opinion: One of the major challenges for developing composite scaffolds for BTE is the incorporation of a drug delivery function of sufficient complexity to be able to induce the release patterns that may be necessary for effective osseointegration, vascularization and bone regeneration. Loading 3D scaffolds with different biomolecular agents should produce a codelivery system with different, predetermined release profiles. It is also envisaged that the number of relevant bioactive agents that can be loaded onto scaffolds will be increased, whilst the composite scaffold design should exploit synergistically the different degradation profiles of the organic and inorganic components.     

Nanostructured poly(l-lactide) matrix as novel platform for drug delivery

With the aim to establish new strategies for fabricating bioactive nanostructured matrices for controlled drug delivery or potential tissue engineering, a facile and one-pot protocol was developed in this study to produce drug-loaded poly(l-lactide) (PLLA) nanostructures by thermally induced phase separation. Using both steroidal and nonsteroidal anti-inflammatory drugs, we demonstrated that lipophilic drugs can be efficiently incorporated in either nanosheet-like or nanofibrous PLLA matrices. Thus entrapped drug was randomly distributed in the interconnected nanostructures in the form of nanoscaled crystals. In vitro release study revealed that drug release kinetics may be modulated, on the one hand, by the nanostructure of matrices, while on the other hand by the polymer concentration utilized for fabrication. As for hydrophilic compounds, they could be conveniently loaded into nanofibrous structure by post-fabrication absorption. In addition to the conceptual proof of potential applications of nanostructured PLLA matrices for controlled drug delivery, the strategy employed herein offers a new way to construct bioactive scaffolds, such as antibacterial or anti-inflammatory scaffolds, which may find broad applications for tissue regeneration and stem cells-based biotherapy.     

Effects of the rate of solvent evaporation on the characteristics of drug loaded PLLA and PDLLA microspheres

We investigated the effects of the rate of solvent removal by varying ambient pressure at a fixed temperature on the morphology, particle sizes, drug encapsulation efficiency and releases pattern of lidocaine loaded poly-L-lactatide (PLLA) and poly-D,L-lactatide (PDLLA) microspheres, prepared with O/W emulsion-solvent evaporation process. Prepared in the fast rate of solvent evaporation (FRSE) process by reducing ambient pressure, smoothly morphological surface of drug loaded PLLA and PDLLA microspheres was observed. While in the normal rate of solvent evaporation (NRSE) process, roughness or pinhole surface was only found at drug loaded PLLA microspheres. Fabricated in the FRSE process, both PLLA and PDLLA microspheres showed smaller particle sizes and lower drug encapsulation efficiencies than those prepared in NRSE process. In regard to two materials, PLLA microspheres had higher drug encapsulation efficiencies than PDLLA ones for both processes. Although initial burst releases of drug were observed for both PLLA and PDLLA microspheres prepared in whatever solvent removal process, drug release for PLLA microspheres was slightly less than that for PDLLA ones in the earlier stage of drug release. However, in the subsequent stage of drug release, there was no difference between two materials. In corporation with different crystalline characteristics of PLA polymer and its derivatives, FRSE process by reducing ambient pressure could be further applied to produce different characteristics of microspheres for drug delivery.     

Controlled Release of Simvastatin from In situ Forming Hydrogel Triggers Bone Formation in MC3T3-E1 Cells

Simvastatin (SIM), a drug commonly administered for the treatment of hypercholesterolemia, has been recently reported to induce bone regeneration/formation. In this study, we investigated the properties of hydrogel composed of gelatin–poly(ethylene glycol)–tyramine (GPT) as an efficient SIM delivery vehicle that can trigger osteogenic differentiation. Sustained delivery of SIM was achieved through its encapsulation in an injectable, biodegradable GPT-hydrogel. Cross-linking of the gelatin-based GPT-hydrogel was induced by the reaction of horse radish peroxidase and H₂O₂. GPT-hydrogels of three different matrix stiffness, 1,800 (GPT-hydrogel1), 5,800 (GPT-hydrogel2), and 8,400 Pa (GPT-hydrogel3) were used. The gelation/degradation time and SIM release profiles of hydrogels loaded with two different concentrations of SIM, 1 and 3 mg/ml, were also evaluated. Maximum swelling times of GPT-hydrogel1, GPT-hydrogel2, and GPT-hydrogel3 were observed to be 6, 12, and 20 days, respectively. All GPT-hydrogels showed complete degradation within 55 days. The in vitro SIM release profiles, investigated in PBS buffer (pH 7.4) at 37°C, exhibited typical biphasic release patterns with the initial burst being more rapid with GPT-hydrogel1 compared with GPT-hydrogel3. Substantial increase in matrix metalloproteinase-13, osteocalcin expression levels, and mineralization were seen in osteogenic differentiation system using MC3T3-E1 cells cultured with GPT-hydrogels loaded with SIM in a dose-dependent manner. This study demonstrated that controlled release of SIM from a biodegradable, injectable GPT-hydrogel had a promising role for long-term treatment of chronic degenerative diseases such as disc degenerative disease.     

Effective combination of aligned nanocomposite nanofibers and human unrestricted somatic stem cells for bone tissue engineering

Aim:

Bioartificial bone tissue engineering is an increasingly popular technique to solve bone defect challenges. This study aimed to investigate the interactions between matrix composition and appropriate cell type, focusing on hydroxyapatite (HA), to achieve a more effective combination for bone regeneration.

Methods:

Human unrestricted somatic stem cells (USSCs) were isolated from placental cord blood. The cellular and molecular events during the osteo-induction of USSCs were evaluated for 21 d under the following conditions: (1) in basal culture, (2) supplemented with hydroxyapatite nanoparticle (nHA) suspension, and (3) seeded on electrospun aligned nanofibrous poly-ɛ-caprolactone/poly-L-lactic acid/nHA (PCL/PLLA/nHA) scaffolds. The scaffolds were characterized using scanning electron microscope (SEM), fourier transform infrared spectroscopy (FTIR) and tensile test.

Results:

Maintenance of USSCs for 21 d in basal or osteogenic culture resulted in significant increase in osteoblast differentiation. With nHA suspension, even soluble osteo-inductive additives were ineffective, probably due to induced apoptosis of the cells. In contrast to the hindrance of proliferation by nHA suspension, the scaffolds improved cell growth. The scaffolds mimic the nanostructure of natural bone matrix with the combination of PLLA/PCL (organic phase) and HA (inorganic phase) offering a favorable surface topography, which was demonstrated to possess suitable properties for supporting USSCs. Quantitative measurement of osteogenic markers, enzymatic activity and mineralization indicated that the scaffolds did not disturb, but enhanced the osteogenic potential of USSCs. Moreover, the alignment of the fibers led to cell orientation during cell growth.

Conclusion:

The results demonstrated the synergism of PCL/PLLA/nHA nanofibrous scaffolds and USSCs in the augmentation of osteogenic differentiation. Thus, nHA grafted into PCL/PLLA scaffolds can be a suitable choice for bone tissue regeneration.     

Preparation of biodegradable microspheres containing water-soluble drug, β-lactam antibiotic

Poly (l-lactic acid) (PLLA) microspheres loaded with ampicillin sodium (AMP-Na), β-lactam antibiotic, were prepared by a w/o/w multiple emulsion-solvent evaporation method. The amounts of each component in three phases (inner water phase, organic phase, and outer water phase) were carefully examined in the preparation of PLLA microspheres. The stirring rate, another preparation parameter, was also investigated for study on the effect of mechanical stress on the drug loading and morphology of PLLA microspheres. Most of the preparation parameters had a great influence on the drug loading, surface morphology and size distribution of PLLA microspheres. PLLA microspheres with 15.89 w/w% drug loading were subjected to thein vitro release experiment. The release of ampicillin sodium was constant at a rate of 1.68 μg/ml/day per 1 mg of microspheres for 18 days after a 4 days initial burst effect.     

Microsphere-based drug releasing scaffolds for inducing osteogenesis of human mesenchymal stem cells in vitro

In this study, in vitro osteogenesis was successfully achieved in human mesenchymal stem cells (hMSCs) by controlled release of the osteogenesis-inducing drugs dexamethasone, ascorbic acid (AA) and β-glycerophosphate (GP) from poly(lactic-co-glycolic acid) (PLGA) sintered microsphere scaffolds (SMS). We investigated the osteogenesis of human MSCs (hMSCs) on dexamethasone laden PLGA-SMS (PLGA-Dex-SMS), and dexamethasone, AA and GP laden PLGA-SMS (PLGA-Com-SMS). hMSCs cultured on the microsphere systems, which act as drug release vehicles and also promote cell growth/tissue formation—displayed a strong osteogenic commitment locally. The osteogenic commitment of hMSCs on the scaffolds were verified by alkaline phosphatase (ALP) activity assay, calcium secretion assay, real-time PCR and immunohistochemistry analysis. The results indicated hMSCs cultured on PLGA-Com-SMS exhibited superior osteogenic differentiation owing to significantly high phenotypic expression of typical osteogenic genes—osteocalcin (OC), type I collagen, alkaline phosphatase (ALP), and Runx-2/Cbfa-1, and protein secretion of bone-relevant markers such as osteoclast and type I collagen when compared with PLGA-Dex-SMS. In conclusion, by promoting osteogenic development of hMSCs in vitro, this newly designed controlled release system opens a new door to bone reparation and regeneration.     

Development of poly(glycerol adipate) nanoparticles loaded with non-steroidal anti-inflammatory drugs

The aim of this study was to assess acylated and non-acylated poly(glycerol adipate) polymers (PGA) as suitable nanoparticulate systems for encapsulation and release of ibuprofen, ibuprofen sodium salt (IBU-Na) and ketoprofen as model drugs. Drug encapsulated nanoparticles were prepared using the interfacial deposition method in the absence of surfactants. Physicochemical characterisation studies of the produced loaded nanoparticles showed that drug–polymer interactions depend on the characteristics of the actual active substance. IBU-Na showed strong interactions with the polymers and it was found to be molecularly dispersed within the polymer matrix while ibuprofen and ketoprofen retained their crystalline state. The drug release profiles showed stepwise patterns which involve an initial burst release effect, diffusion of the drug from the polymer matrix and eventually drug release possibly via a combined mechanism. PGA polymers can be effectively used as drug delivery carriers for various active substances.     

Methotrexate loaded poly(L-lactic acid) microspheres for intra-articular delivery of methotrexate to the joint

A controlled release delivery system that localizes methotrexate (MTX) in the synovial joint is needed to treat inflammation in rheumatoid arthritis (RA). The purpose of this work was to develop and characterize MTX loaded poly(l-lactic acid) (PLLA) microspheres and evaluate in vivo tolerability and MTX plasma concentrations following intra-articular injection into healthy rabbits. MTX loaded PLLA (2 kg/mole) microspheres were prepared using the solvent evaporation method and characterized in terms of size, molecular weight, thermal properties, and release rates into phosphate buffered saline (PBS) (pH 7.4) at 37 degrees C. Biocompatibility was evaluated by observing the swelling of the joints of the rabbits and histological analysis following the injection of the microspheres. MTX concentrations in the plasma and urine samples of rabbits were evaluated by high-performance liquid chromatography (HPLC). MTX loaded microspheres showed a rapid burst phase followed by a slow release phase. MTX loaded and control microspheres were biocompatible and plasma concentrations of MTX were tenfold higher in rabbits injected intra-articularly with free MTX than MTX microspheres. MTX microspheres may retain the drug in the joint by reducing clearance from the joint into the blood.     

Development of poly(glycerol adipate) nanoparticles loaded with non-steroidal anti-inflammatory drugs

The aim of this study was to assess acylated and non-acylated poly(glycerol adipate) polymers (PGA) as suitable nanoparticulate systems for encapsulation and release of ibuprofen, ibuprofen sodium salt (IBU-Na) and ketoprofen as model drugs. Drug encapsulated nanoparticles were prepared using the interfacial deposition method in the absence of surfactants. Physicochemical characterisation studies of the produced loaded nanoparticles showed that drug-polymer interactions depend on the characteristics of the actual active substance. IBU-Na showed strong interactions with the polymers and it was found to be molecularly dispersed within the polymer matrix while ibuprofen and ketoprofen retained their crystalline state. The drug release profiles showed stepwise patterns which involve an initial burst release effect, diffusion of the drug from the polymer matrix and eventually drug release possibly via a combined mechanism. PGA polymers can be effectively used as drug delivery carriers for various active substances.     

Therapeutic applications of electrospun nanofibers for drug delivery systems

Electrospun nanofiber drug delivery systems have been studied using various techniques. Herein, we describe the fabrication of a drug-incorporating nanofiber. Drugs, such as proteins, peptide, antibodies, and small molecule drugs, can be loaded within or on the surface of nanofibers according to their properties. Hydrophobic drugs are directly dissolved with a polymer in an organic solvent before electrospinning. However, it is preferred to surface-immobilize bioactive molecules on nanofibers by physical absorption or chemical conjugation. Especially, chemically surface-immobilized proteins on a nanofiber mesh stimulate cell differentiation and proliferation. Using a dual electrospinning nozzle to create nanofiber sheet layers, which are stacked on top of one another, the initial burst release is reduced compared with solid nanofibers because of the layers. Furthermore, hybridization of electrospun nanofibers with nanoparticles, microspheres, and hydrogels is indirect drug loading method into the nanofibers. It is also possible to produce multi-drug delivery systems with timed programmed release.     

Controlling protein release from scaffolds using polymer blends and composites.

We report the development of three protein loaded polymer blend and composite materials that modify the release kinetics of the protein from poly(dl-lactic acid) (P(dl)LA) scaffolds. P(dl)LA has been combined with either poly(ethylene glycol) (PEG), poly(caprolactone) (PCL) microparticles or calcium alginate fibres using supercritical CO(2) (scCO(2)) processing to form single and dual protein release scaffolds. P(dl)LA was blended with the hydrophilic polymer PEG using scCO(2) to increase the water uptake of the resultant scaffold and modify the release kinetics of an encapsulated protein. This was demonstrated by the more rapid release of the protein when compared to the release rate from P(dl)LA only scaffolds. For the P(dl)LA/alginate scaffolds, the protein loaded alginate fibres were processed into porous protein loaded P(dl)LA scaffolds using scCO(2) to produce dual release kinetics from the scaffolds. Protein release from the hydrophilic alginate fibres was more rapid in the initial stages, complementing the slower release from the slower degrading P(dl)LA scaffolds. In contrast, when protein loaded PCL particles were loaded into P(dl)LA scaffolds, the rate of protein release was retarded from the slow degrading PCL phase.     

知母皂苷B-Ⅱ纳米纤维膜制备及体外抗肿瘤活性的初步研究

目的探索知母皂苷B-Ⅱ纳米纤维膜的制备方法,为后续进行体内相关研究打好基础.方法：将知母皂苷B-Ⅱ与聚乳酸（PLLA）按照不同比例制成知母皂苷B-Ⅱ纳米纤维膜;分别采用扫描电镜、红外光谱分析、LC-MS/MS 检测方法对纤维膜理化性质表征、生物相容性、缓释性能等进行测试;采用CCK-8法检测载药纳米膜缓释药物抑制胃癌细胞的增殖情况.结果：12%的知母皂苷B-Ⅱ浓度为最佳载药浓度;在制备载知母皂苷B-Ⅱ纳米纤维的过程中,静电纺丝技术能保持两种组分各自的化学特征及物理性质;知母皂苷B-Ⅱ对纤维膜的热稳定性影响不大,两者相容性较好;知母皂苷B-Ⅱ纳米纤维膜可有效释放知母皂苷B-Ⅱ,明显抑制BGC-823细胞的增殖活性,在48 h、72 h 与对照组细胞相比较,差异具有统计学意义（P 〈0.05）.结论：知母皂苷B-Ⅱ纳米纤维膜通过缓释药物可有效抑制BGC-823细胞的增殖能力.     

Construction and performance of exendin-4-loaded chitosan–PLGA microspheres for enhancing implant osseointegration in type 2 diabetic rats

The updating and optimization of drug delivery systems is critical for better in vivo behaviors of drugs, as well as for improving impaired implant osseointegration in diabetes. Numerous studies have reported the benefits of exendin-4 on diabetic bone, with the potential to enhance osseointegration in diabetes. To construct an appropriate sustained-release system of exendin-4 targeting implant osseointegration in diabetes, this study fabricated exendin-4-loaded microspheres using poly(lactic-co-glycolic acid) (PLGA) and chitosan. The morphology, size, encapsulation efficiency, and drug release behavior of microspheres were investigated. The bioactivity of drug-loaded microspheres on cell proliferation and osteogenic differentiation of diabetic BMSCs was investigated to examine the pharmacologic action of exendin-4 loaded into chitosan–PLGA microspheres. Further, the influence of microspheres on osseointegration was evaluated using type 2 diabetes mellitus (T2DM) rat implant model. After 4 weeks, the samples were evaluated by radiological and histological analysis. The results of in vitro experiments showed that the prepared exendin-4-loaded chitosan–PLGA microspheres have good properties as a drug delivery system, and the chitosan could improve the encapsulation efficiency and drug release of PLGA microspheres. In addition, exendin-4-loaded microspheres could enhance the proliferation and osteogenic differentiation of diabetic BMSCs. The results of in vivo experiments showed the exendin-4-loaded microspheres significantly improved the impaired osseointegration and bone formation around implants in T2DM rats without affecting blood glucose levels. Thus, the local application of exendin-4-loaded chitosan–PLGA microspheres might be a promising therapeutic strategy for improving the efficacy of dental implants in T2DM individuals.     

Characterisation of protein stability in rod-insert vaginal rings

A series of mesocellular foams (MCFs)-based mesoporous silica nanospheres (DH-MCF-P123-n, (n=12, 2, 0.5)) were synthesized as controlled-release deliveries for a typical antidepressant drug, venlafaxine. The foams were 3-(2,3-dihydroxypropoxyl)propyl-grafted and the P123 template partially preserved. We studied the release profiles of venlafaxine-loaded DH-MCF-P123-n in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF), respectively, as well as their corresponding venlafaxine loading capacities. Appropriate amounts of P123 template preserved in mesopores showed an efficient synergetic effect on increasing venlafaxine loading capacity and controlled-release property. Up to 90.87% (mass fraction) of venlafaxine could be loaded into DH-MCF-P123-2. For this carrier, 36% of venlafaxine was released after 1h of incubation in SGF and 53% of venlafaxine was released after 12h in SIF. The mechanisms of the loading and releasing processes were tentatively described based on the release behaviors.     

抗骨结核载药缓释支架的研究进展

骨结核是除肺结核以外发病率最高的结核,占全部结核发病率的3％～5％,占肺外结核发病率的35％～50％.目前,临床治疗一般是用手术清除病灶部位的坏死组织,然后再放置抗结核药物以杀死残留的结核杆菌,但是放置的抗结核药物粉末易被体液冲走.载药骨支架既具有充填重建、诱导成骨作用,又能立体局部持续缓慢释放抗结核药物,能够大大提高抗结核药物的疗效并降低副作用,具有很高的临床价值.本文对抗骨结核载药缓释支架的最新研究进展进行综述,为新型抗结核载药缓释骨支架的设计提供思路.     

Effects of solvent evaporation rate on the properties of protein-loaded PLLA and PDLLA microspheres fabricated by emulsion-solvent evaporation process

This paper investigated the effects of the rate of solvent removal by varying the ambient pressure at a fixed temperature on the morphology, particle size, encapsulation efficiency and release pattern of albumin-loaded PLLA and PDLLA microspheres, prepared by the W/O/W emulsion-solvent evaporation process. For PLLA microspheres prepared either with a fast rate of solvent evaporation (FRSE) or a normal rate of solvent evaporation (NRSE) process, the difference in morphology was minor. In contrast, the different processes did affect the morphology of PDLLA microspheres. Large (surface) pores were observed for PDLLA microspheres fabricated with a FRSE process, while a smooth surface was seen in those with a NRSE process. With the FRSE process, both PLLA and PDLLA microspheres showed smaller particle sizes and lower albumin encapsulation efficiencies than those prepared in the NRSE process. PLLA microspheres prepared with the NRSE process had higher drug encapsulation efficiencies than PDLLA ones, but this was not the case for the FRSE process. An initial burst release of albumin was observed for both PLLA and PDLLA microspheres prepared with the NRSE process, while a lesser burst release was seen for those prepared with the FRSE process. In subsequent stages of drug release, PLLA microspheres prepared with the two different processes showed differences, but this was not the case for PDLLA ones.     

Preparation of chitosan-gelatin scaffold containing tetrandrine-loaded nano-aggregates and its controlled release behavior

A well-timed delivery of bioactive macromolecules from the porous scaffolds is very important in tissue engineering. Tetrandrine (Ted) is one of a large number of known plant derived bisbenzylisoquinoline alkaloids and is obtained from the roots of Stephania tetrandria. Ted can be used as a modifier to poly(l-lactic acid) scaffolds to promote chondrocyte differentiation and secrete type II collagen. But the effect of Ted on chondrocyte's behavior strongly depends on the concentration of Ted in the culture media. Here amphiphilic diblock copolymer (PLAE) composed of l-lactide and methoxy poly(ethylene glycol) (MePEG) was prepared and the Ted loaded copolymeric nanospheres were obtained by self-emulsification and then solvent evaporation. The mean sizes of core/shell type PLAE nanospheres and Ted-loaded nanospheres are about 60 and 100 nm, respectively. Chitosan–gelatin (Cs–Gel) porous scaffolds loaded with PLAE–Ted nanospheres were fabricated through freeze drying. Ted release behaviors from PLAE–Ted nanospheres and porous scaffolds were investigated. The result shows that the Ted-loaded nanospheres could be embedded within Cs–Gel scaffolds and no initial burst release could be observed in the release patterns. Here a room can be provided for the scaffolds to sustained release bioactive component in tissue engineering.