Characterization of Poly(ε-caprolactone)/Polyfumarate Blends as Scaffolds for Bone Tissue Engineering

There is considerable interest in the design of polymeric biomaterials that can be used for the repair of bone defects. In this study, we used ultrasound to prepare a compatibilized blend of poly(ε-caprolactone) (PCL) and poly(diisopropyl fumarate) (PDIPF). The formation of post-sonication inter-polymer coupling products was verified by SEC analysis of a blend with azo-labeled PDIPF. We also analyzed the physicochemical and mechanical properties of the compatibilized blend. When compared to PCL alone, the PCL/PDIPF blend showed no difference in its resistance as evaluated by the elastic modulus, although it did show a 50% decrease in ultimate tensile stress (P < 0.05) and an 84% decrease in elongation-at-break (P < 0.05). However, the mechanical properties of this blend were comparable to those of trabecular bone. We next evaluated biocompatibility of the PCL/PDIPF blend, and of homo-polymeric PCL and PDIPF films for comparison, with UMR106 and MC3T3E1 osteoblastic cells. Osteoblasts plated on the compatibilized blend adhered and proliferated more than on either homo-polymer, showed a greater number of cellular processes with a better organized actin cytoskeleton and expressed more type-I collagen and mineral, both markers of osteoblast phenotype. These results support the hypothesis that this new compatibilized blend could be useful in future applications for bone regeneration.     

Polyvinyl Alcohol-Collagen Composite with Glycosaminoglycan as Scaffolds for Tissue Engineering

The aim of this study is to prepare a PVA-GAG-COL composite material by polyvinyl alcohol （ PVA）, glycosaminoglycan （GAG） and collagen （COL） ,and to investigate the feasibility of serving as a scaffold for tissue engineering. PVA was blended with various amounts of GAG and COL. Different proportional scaffolds could be obtained with different molecular weight and alcoholysis degree of PVA and different amounts of GAG, which exhibited high water content （60% -95% ） and showed different inner configuration with swelling ratio （ 120% - 620% ）. SEM proved that different composite materials had different porous structures.     

Novel Melt-Processable Chitosan–Polybutylene Succinate Fibre Scaffolds for Cartilage Tissue Engineering

Novel chitosan/polybutylene succinate fibre-based scaffolds (C-PBS) were seeded with bovine articular chondrocytes in order to assess their suitability for cartilage tissue engineering. Chondrocytes were seeded onto C-PBS scaffolds using spinner flasks under dynamic conditions, and cultured under orbital rotation for a total of 6 weeks. Non-woven polyglycolic acid (PGA) felts were used as reference materials. Tissue-engineered constructs were characterized by scanning electron microscopy (SEM), hematoxylin–eosin (H&E), toluidine blue and alcian blue staining, immunolocalization of collagen types I and II, and dimethylmethylene blue (DMB) assay for glycosaminoglycans (GAG) quantification at different time points. SEM showed the chondrocytes' typical morphology, with colonization at the surface and within the pores of the C-PBS scaffolds. These observations were supported by routine histology. Toluidine blue and alcian blue stains, as well as immunohistochemistry for collagen types I and II, provided qualitative information on the composition of the engineered extracellular matrix. More pronounced staining was observed for collagen type II than collagen type I. Similar results were observed with constructs engineered on PGA scaffolds. These also exhibited higher amounts of matrix glycosaminoglycans and presented a central region which contained fewer cells and little matrix, a feature that was not detected with C-PBS constructs.     

Tissue Engineering Applications for Ligament and Tendon Reconstruction

Tendons and ligaments are subjected to high physiological loads. As such, injuries due to high impact activities are common. Due to the avascular nature of these connective tissues, the healing rate is rather slow. Currently the therapeutic options to treat tendon and ligament injuries are autografts, allografts and prosthetic devices. However, there are many disadvantages in using biological grafts, as well as concerns over long-term performance of synthetic prostheses. Therefore, further re…     

The Effect of Hybridization of Hydrogels and Poly(L-lactide-co-ε-caprolactone) Scaffolds on Cartilage Tissue Engineering

For repairing cartilage defects by cartilage tissue engineering, it is important that engineered cartilage that is fabricated with scaffolds and cells can maintain the biological and physiological functions of cartilage, and also can induce three-dimensional spatial organization of chondrocytes. In this sense, hydrogels such as fibrin gels (FG) and hyaluronan (HA) are widely used for application in cartilage treatment. However, the use of hydrogels alone as a scaffold has a physical weakness; the mechanical properties of hydrogels are too weak to endure complex loading in the body. In this study, for mimicking a native cartilage microenvironment, we made cell–hybrid scaffold constructs with poly(L-lactide-co-ε-caprolactone) (PLCL) scaffolds and hydrogels to guide three-dimensional spatial organization of cells and extracellular matrix. A highly elastic scaffold was fabricated from PLCL with 85% porosity and 300–500 μm pore size using a gel-pressing method. The mixture of rabbit chondrocytes and hydrogels was seeded on PLCL scaffolds, and was subcutaneously implanted into nude mice for up to eight weeks. The cell seeding efficiency of the hybrid scaffolds with FG or HA was higher than that of the PLCL scaffolds. From in vivo studies, the accumulation of cartilaginous extracellular matrices of constructs, which was increased by hybridization of hydrogels and PLCL scaffolds, showed that the cell–hybrid scaffold constructs formed mature and well-developed cartilaginous tissue. In conclusion, the hybridization of hydrogels and PLCL scaffold for three-dimensional spatial organization of cells would provide a biomimetic environment where cartilage tissue growth is enhanced and facilitated. It can enhance the production of cartilaginous extracellular matrices and, consequently, improve the quality of the cartilaginous tissue formed.     

A Viscoelastic Chitosan-Modified Three-Dimensional Porous Poly(L-Lactide-co-ε-Caprolactone) Scaffold for Cartilage Tissue Engineering

Biomaterials have been playing important roles in cartilage regeneration. Although many scaffolds have been reported to enhance cartilage regeneration, none of the scaffolds available are optimal regarding mechanical properties, integration with host cartilage and providing proper micro-environment for chondrocyte attachment, proliferation and differentiation. In the current study, chitosan-modified poly(L-lactide-co-ε-caprolactone) (PLCL) scaffolds were fabricated to simulate the main biochemical components of cartilage, as well as their interaction with the aim to endow them with viscoelasticity similar to native cartilage. Porous PLCL scaffolds were fabricated with porogen-leaching, freeze-extraction and freeze-gelation before chitosan was cross-linked. The acquired porous scaffolds had pore sizes ranging from 200 to 500 μm and about 85% porosity with good interconnection between individual pores. Chitosan was successfully cross-linked to PLCL scaffolds, as validated by ninhydrin staining and X-ray photoelectron spectroscopy (XPS). The viscoelasticity of the scaffolds was similar to that of bovine cartilage and they had a relatively good recovery ratio from compression deformation, while the Young's modulus was one order of magnitude less than cartilage. Not only could the chitosan-modified PLCL scaffolds promote cell adhesion and proliferation, but also they could significantly enhance excretion of aggrecan and type-II collagen, as testified by both histology and quantitative PCR, compared with PLCL scaffolds. With the fabrication of biomimetic scaffolds, it is possible to make scaffolds for cartilage tissue engineering, which are not only biocompatible, but also have mechanical properties similar to native cartilage.     

A Poloxamine–Polylysine Acrylate Scaffold for Modular Tissue Engineering

A new polymer, poloxamine–polylysine acrylate (PPA), was synthesized for tissue-engineering applications. Polylysine was used to confer endothelial cell attachment properties to the poloxamine-based polymer, while the acrylate groups made it photo-cross-linkable. The PPA polymer was synthesized in three reaction steps. (1) Polylysine was acrylated using N-hydroxysuccinimide acrylic acid ester and the reaction product was characterised by ¹H-NMR. (2) The hydroxyl groups on poloxamine were activated by tresylation with tresyl chloride and the reaction product (tresylated poloxamine) was characterised by ICP-AES for sulphur content. (3) The acrylated polylysine was reacted with the activated poloxamine to obtain the final product, poloxamine–polylysine acrylate. The final product was characterised by CHN elemental analysis. Aqueous solutions containing a mixture of PPA and poloxamine methacrylate were photo-cross-linked by exposure to a 365 nm UV light source in the presence of a photoinitiator to obtain hydrogels. The synthesized PPA polymer enhanced endothelial cell adhesion on poloxamine-based, photo-cross-linked hydrogel scaffolds. The same synthesis methods can be used in the future to introduce other desired functions (through other peptides) into the scaffold biomaterial.     

Cell Attachment–Detachment Control on Temperature-Responsive Thin Surfaces for Novel Tissue Engineering

Temperature-responsive intelligent surfaces, prepared by the modification of an interface mainly with poly(N-isopropylacrylamide) and its derivatives, have been investigated. Such surfaces exhibit temperature-responsive hydrophilic/hydrophobic alterations with external temperature changes, which, in turn, result in thermally modulated attachment and detachment with cells. The advantage of this system is that cells cultured on such temperature-responsive surfaces can be recovered as single cells and/or confluent cell sheets, while keeping the deposited extracellular matrix intact, simply by lowering the temperature without conventional enzymatic treatment. Here, we focus and compare various methods of producing temperature-responsive surfaces for controlling cell attachment/detachment. Spontaneous cell attachment and detachment using several types of temperature-responsive surfaces are mentioned and various effects, such as film thickness and polymer conformation, are discussed. In addition, the development of the next generation of temperature-responsive surfaces using modifications of the polymer coating to allow for rapid cell recovery is summarized.     

Biocomposites Electrospun with Poly(ε-caprolactone) and Silk Fibroin Powder for Biomedical Applications

Biomedical synthetic polymers have been used in soft and hard tissue regeneration because of their good processability and biodegradability. However, biomaterials such as poly(ε-caprolactone) (PCL) have various shortcomings, including intrinsic hydrophobicity and lack of bioactive functional groups. The material must be reinforced with natural biomaterials to achieve good cellular and mechanical performance as biomedical material. We fabricated a biocomposite using PCL and silk fibroin (SF) powder, which has good biocompatibility and mechanical properties. The hydrophilicity, mechanical properties and cellular behavior of the PCL/SF fibers were analyzed. In addition, we obtained a highly oriented conduit of electrospun biocomposite fibers by modifying the rolling collector of the electrospinning system. As the alignment of micro/nanofibers increased, the orthotropic mechanical properties were improved. The biocompatibility of the biocomposite was evaluated in a culture of bone-marrow-derived rat mesenchymal stem cells. The cellular result demonstrated the potential usefulness of electrospun biocomposites for various biomedical conduit systems.     

Study on Galactose–Poly(Ethylene Glycol)–Poly(L-Lysine) as Novel Gene Vector for Targeting Hepatocytes In Vitro

A non-viral gene-delivery system has been used to deliver plasmid DNA into specific cell types because of its safety and ease of manufacture. Receptor-mediated gene transfer is currently a promising gene-delivery technique. To specifically target genes to asialoglycoprotein receptor of hepatocytes, a galactose moiety was combined into the poly(ethylene glycol) (PEG)-terminal end by reductive coupling using lactose and sodium cyanoborohydride. A synthesis method of conjugating poly(L-lysine) (PLL) derivatives with terminally galactose-graft-PEG was developed using ring-opening polymerization of N ^ε -benzyloxycarbonyl-L-lysine-N ^α -carboxyan-hydride (Z-Lys-NCA) initiated onto galactose graft amine-terminated PEG (galactose–PEG–NH₂) as a macro-initiator. The synthesis was characterized with ¹H-, ¹³C-NMR, IR and UV spectroscopy, and all of them successfully verified the formation of the co-polymers. The gel-retardation assay of the complexes between galactose–PEG–PLL and plasmid DNA indicated that these polymeric gene carriers demonstrated the potent ability to condense plasmid DNA electrostatically as well as PLL. The particle size and zeta potential of polymer/DNA complexes were measured, and their cytotoxicity and transfection efficiency in different cells were evaluated. The results indicate that galactose–PEG–PLL can form a complex with plasmid DNA and serve as an effective gene-delivery carrier with lower cytotoxicity compared to that of PLL. Transfection experiments clearly showed that galactose–PEG–PLL effectively delivered DNA into hepatoma cells in vitro. Such data demonstrates that galactose and its complex with plasmid DNA may serve as a safe and effective gene-transfer system targeting hepatocytes.     

Electrospun Poly(L-Lactic Acid)-co-Poly(ϵ-Caprolactone) Nanofibres Containing Silver Nanoparticles for Skin-Tissue Engineering

Abstract

Silver nanoparticles (AgNPs) and silver ions (Ag⁺) show growth-inhibitory activity against microorganisms and have been used for decades as antibacterial agents in various fields. To fabricate a nanofibrous scaffold which is antibacterial against bacteria and non-toxic to cells, we electrospun composite poly(L-lactic acid)-co-poly(?-caprolactone) nanofibres containing silver nanoparticles (PLLCL-AgNPs) with different concentrations (0.25, 0.50 and 0.75 wt%) of silver nitrate (AgNO₃) in PLLCL. The diameters of the electrospun PLLCL-AgNPs nanofibres decreased with the increase of AgNO₃ concentration in PLLCL solutions. Human skin fibroblasts cultured on the scaffolds showed that the PLLCL nanofibres containing lesser amounts of AgNPs (0.25 wt%) had better cell proliferation and retained the cell morphology similar to the phenotype observed on tissue culture plates (control). The antibacterial activity of AgNPs in PLLCL nanofibres was investigated against Staphylococcus aureus and Salmonella enterica and the antimicrobial activity was found to increase with the increasing concentration of nanoparticles present in the scaffold. Based on our studies, we propose that PLLCL nanofibres containing 0.25 wt% AgNO₃ or PLLCL-Ag(25), favors cell proliferation and inhibits bacteria and could be a suitable substrate for wound healing.     

A Collagen–Poly(Vinyl Alcohol) Nanofiber Scaffold for Cartilage Repair

Articular cartilage has a limited capacity for self-repair. Untreated injuries of cartilage may lead to osteoarthritis. This problem demands new effective methods to reconstruct articular cartilage. Mesenchymal stem cells (MSCs) have the proclivity to differentiate along multiple lineages giving rise to new bone, cartilage, muscle, or fat. This study was an animal model for autologous effects of transplantation of MSCs with a collagen–poly(vinyl alcohol) (PVA) scaffold into full-thickness osteochondral defects of the stifle joint in the rabbit as an animal model. A group of 10 rabbits had a defect created experimentally in the full thickness of articular cartilage penetrated into the subchondral space in the both stifle joints. The defect in the right stifle was filled with MSCs/collagen–PVA scaffold (group I), and in the left stifle, the defect was left without any treatment as the control group (group II). Specimens were harvested at 12 weeks after implantation, examined histologically for morphologic features, and stained immunohistochemically for type-II collagen. Histology observation showed that the MSCs/collagen–PVA repair group had better chondrocyte morphology, continuous subchondral bone, and much thicker newly formed cartilage compared with the control group at 12 weeks post operation. There was a significant difference in histological grading score between these two groups. The present study suggested that the hybrid collagen–PVA scaffold might serve as a new way to keep the differentiation of MSCs for enhancing cartilage repair.     

A New Injectable Thermogelling Material: Methoxy Poly(ethylene glycol)–Poly(sebacic acid-D,L-lactic acid)–Methoxy Poly(ethylene glycol) Triblock Co-polymer

A novel injectable thermogelling poly(ester-anhydride) co-polymer, methoxy poly(ethylene glycol)–poly(sebacic acid-D,L-lactic acid)–methoxy poly(ethylene glycol) (mPEG–poly(SA-LA)–mPEG) triblock co-polymer, was prepared by melt-condensation polymerization. The synthesized triblock co-polymer was characterized by FT-IR and ¹H-NMR. The aqueous solutions of mPEG–poly(SA-LA)–mPEG underwent sol–gel precipitation transition when the temperature was increased from 20 to 70°C, depending on the concentration of the polymer. 5-FU, as the model drug, was mixed into the gel in a low-viscous sol state at room temperature. About 63 wt% of the loaded 5-FU could be released in vitro from the gel over 72 h at 37°C. Subcutaneous injection of 25 wt% mPEG–poly(SA-LA)–mPEG aqueous solution resulted in the formation of a in situ gel depot in a rat model, which sustained for longer time than that of Pluronic F-127 aqueous solution. The biodegradable thermogelling mPEG–poly(SA-LA)–mPEG triblock co-polymer is believed to be a promising candidate for drug-delivery applications.     

Poly(amidoamine) dendrimer–drug conjugates with disulfide linkages for intracellular drug delivery

Understanding and improving drug release kinetics from dendrimer–drug conjugates are key steps to improve their in vivo efficacy. N-Acetyl cysteine (NAC) is an anti-inflammatory agent with significant potential for clinical use in the treatment of neuroinflammation, stroke and cerebral palsy. There is a need for delivery of NAC which can enhance its efficacy, reduce dosage and prevent it from binding plasma proteins. For this purpose, a poly(amidoamine) dendrimer–NAC conjugate that contains a disulfide linkage was synthesized and evaluated for its release kinetics in the presence of glutathione (GSH), cysteine (Cys), and bovine serum albumin (BSA) at both physiological and lysosomal pH. The results indicate that the prepared conjugate can deliver ～60% of its NAC payload within 1 h at intracellular GSH concentrations at physiological pH, whereas the conjugate did not release any drug at plasma GSH levels. The stability of the conjugate in the presence of bovine serum albumin at plasma concentrations was also demonstrated. The efficacy of the dendrimer–NAC conjugate was measured in activated microglial cells (target cells in vivo) using the reactive oxygen species (ROS) assay. The conjugates showed an order of magnitude increase in antioxidant activity compared to free drug. When combined with intrinsic and ligand-based targeting with dendrimers, these types of GSH sensitive nanodevices can lead to improved drug release profiles and in vivo efficacy.     

Hollow fibers of poly(lactide-co-glycolide) and poly(ε-caprolactone) blends for vascular tissue engineering applications

At present the manufacture of small-diameter blood vessels is one of the main challenges in the field of vascular tissue engineering. Currently available vascular grafts rapidly fail due to development of intimal hyperplasia and thrombus formation. Poly(lactic-co-glycolic acid) (PLGA) hollow fiber (HF) membranes have previously been proposed for this application, but as we show in the present work, they have an inhibiting effect on cell proliferation and rather poor mechanical properties. To overcome this we prepared HF membranes via phase inversion using blends of PLGA with poly(ε-caprolactone) (PCL). The influence of polymer composition on the HF physicochemical properties (topography, water transport and mechanical properties) and cell attachment and proliferation were studied. Our results show that only the ratio PCL/PLGA of 85/15 (PCL/PLGA85/15) yielded a miscible blend after processing. A higher PLGA concentration in the blend led to immiscible PCL/PLGA phase-separated HFs with an inhomogeneous morphology and variation in the cell culture results. In fact, the PCL/PLGA85/15 blend, which had the most homogeneous morphology and suitable pore structure, showed better human adipose stem cell (hASC) attachment and proliferation compared with the homopolymers. This, combined with the good mechanical and transport properties, makes them potentially useful for the development of small-caliber vascular grafts.     

Poly(vinyl alcohol)/poly(acrylic acid) hydrogel coatings for improving electrode–neural tissue interface

A major problem which hinders the applications of neural prostheses is the inconsistent performance caused by tissue responses during long-term implantation. The study investigated a new approach for improving the electrode–neural tissue interface. Hydrogel poly(vinyl alcohol)/poly(acrylic acid) interpenetrating polymer networks (PVA/PAA IPNs) were synthesized and tailored as coatings for poly(dimethylsiloxane) (PDMS) based neural electrodes with the aid of plasma pretreatment. Changes in the electrochemical impedance and maximum charge injection (Q_inj) limits of the coated iridium oxide microelectrodes were negligible. Protein adsorption on PDMS was reduced by ～85% after coating. In the presence of nerve growth factor (NGF), neurite extension of rat pheochromocytoma (PC12) cells was clearly greater on PVA/PAA IPN films than on PDMS substrates. Furthermore, the tissue responses of PDMS implants coated with PVA/PAA IPN films were studied by 6-week implantation in the cortex of rats, which found that the glial fibrillary acidic protein (GFAP) immunoreactivity in animals (n = 8) receiving coated implants was significantly lower (p < 0.05) compared to that of uncoated implants (n = 7) along the entire distance of 150 μm from the outer skirt to the implant interface. The coated film remained on the surface of the explanted implants, confirmed by scanning electron microscopy (SEM). All of these suggest the hydrogel coating is feasible and favorable to neural electrode applications.     

Poly(lactic acid-co-glycolic acid)–poly(ethylene glycol)–poly(lactic acid-co-glycolic acid) thermogel as a novel submucosal cushion for endoscopic submucosal dissection

Endoscopic submucosal dissection (ESD) is a clinical therapy for early stage neoplastic lesions in the gastrointestinal tract. It is, however, faced with a crucial problem: the high occurrence of perforation. The formation of a submucosal fluid cushion (SFC) via a fluid injection is the best way to avoid perforation, and thus an appropriate biomaterial is vital for this minimally invasive endoscopic technique. In this study, we introduced an injectable thermogel as a novel submucosal injection substance in ESD. The hydrogel synthesized by us was composed of poly(lactic acid-co-glycolic acid)–poly(ethylene glycol)–poly(lactic acid-co-glycolic acid) (PLGA–PEG–PLGA) triblock copolymers. The polymer/water system was a low-viscosity fluid at room temperature and thus easily injected, and turned into a non-flowing gel at body temperature after injection. The submucosal injection of the thermogel to create SFCs was performed in both resected porcine stomachs and living minipigs. High mucosal elevation with a clear margin was maintained for a long duration. Accurate en bloc resection was achieved with the assistance of the thermogel. The mean procedure time was strikingly reduced. Meanwhile, no obvious bleeding, perforation and tissue damage were observed. The application of the thermogel not only facilitated the ESD procedure, but also increased the efficacy and safety of ESD. Therefore, the PLGA–PEG–PLGA thermogel provides an excellent submucosal injection system, and has great potential to improve the ESD technique significantly.     

Chitosan–poly(lactide-co-glycolide) microsphere-based scaffolds for bone tissue engineering: In vitro degradation and in vivo bone regeneration studies

Natural polymer chitosan and synthetic polymer poly(lactide-co-glycolide) (PLAGA) have been investigated for a variety of tissue engineering applications. We have previously reported the fabrication and in vitro evaluation of a novel chitosan/PLAGA sintered microsphere scaffold for load-bearing bone tissue engineering applications. In this study, the in vitro degradation characteristics of the chitosan/PLAGA scaffold and the in vivo bone formation capacity of the chitosan/PLAGA-based scaffolds in a rabbit ulnar critical-sized-defect model were investigated. The chitosan/PLAGA scaffold showed slower degradation than the PLAGA scaffold in vitro. Although chitosan/PLAGA scaffold showed a gradual decrease in compressive properties during the 12-week degradation period, the compressive strength and compressive modulus remained in the range of human trabecular bone. Chitosan/PLAGA-based scaffolds were able to guide bone formation in a rabbit ulnar critical-sized-defect model. Microcomputed tomography analysis demonstrated that successful bridging of the critical-sized defect on the sides both adjacent to and away from the radius occurred using chitosan/PLAGA-based scaffolds. Immobilization of heparin and recombinant human bone morphogenetic protein-2 on the chitosan/PLAGA scaffold surface promoted early bone formation as evidenced by complete bridging of the defect along the radius and significantly enhanced mechanical properties when compared to the chitosan/PLAGA scaffold. Furthermore, histological analysis suggested that chitosan/PLAGA-based scaffolds supported normal bone formation via intramembranous formation.     

Poly(lactide)–vitamin E derivative/montmorillonite nanoparticle formulations for the oral delivery of Docetaxel

Four systems of nanoparticles of biodegradable polymers were developed in this research for oral delivery of anticancer drugs with Docetaxel used as a model drug, which include the poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs), the poly(lactide)–vitamin E TPGS nanoparticles (PLA–TPGS NPs), the poly(lactic-co-glycolic acid)–montmorillonite nanoparticles (PLGA/MMT NPs) and the poly(lactide)–vitamin E TPGS/montmorillonite nanoparticles (PLA–TPGS/MMT NPs). Vitamin E TPGS stands for d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), which is a water-soluble derivative of natural vitamin E formed by esterification of vitamin E succinate with polyethylene glycol (PEG) 1000. The design was made to take advantages of TPGS in nanoparticle technology such as high emulsification effects and high drug encapsulation efficiency, and those in drug formulation such as high cellular adhesion and adsorption. MMT of similar effects is also a detoxifier, which may cure some side effects caused by the formulated drug. The drug-loaded NPs were prepared by a modified solvent extraction/evaporation method and then characterized for their MMT content, size and size distribution, surface charge and morphology, physical status and encapsulation efficiency of the drug in the NPs, and in vitro drug release profile. Cellular uptake of the coumarin 6-loaded NPs was investigated. In vitro cancer cell viability experiment showed that judged by IC₅₀, the PLA–TPGS/MMT NP formulation was found 2.89, 3.98, 2.12-fold more effective and the PLA–TPGS NP formulation could be 1.774, 2.58, 1.58-fold more effective than the Taxotere^® after 24, 48, 72 h treatment, respectively. In vivo PK experiment with SD rats showed that oral administration of the PLA–TPGS/MMT NP formulation and the PLA–TPGS NP formulation could achieve 26.4 and 20.6 times longer half-life respectively than i.v. administration of Taxotere^® at the same 10 mg/kg dose. One dose oral administration of the NP formulations could realize almost 3 week sustained chemotherapy in comparison of 22 h of i.v. administration of Taxotere^®. The oral bioavailability can be enhanced from 3.59% for Taxotere^® to 78% for the PLA–TPGS/MMT NP formulation and 91% for the PLA–TPGS NP formulation respectively. Oral chemotherapy by nanoparticles of biodegradable polymers is feasible.