The synthesized transporter K16APoE enabled the therapeutic HAYED peptide to cross the blood-brain barrier and remove excess iron and radicals in the brain, thus easing Alzheimer's disease.

Alzheimer's disease (AD) is currently incurable and places a large burden on the caregivers of AD patients. In the AD brain, iron is abundant, catalyzing free radicals and impairing neurons. The blood-brain barrier hampers antidementia drug delivery via circulation to the brain, which limits the therapeutic effects of drugs. Here, according to the method described by Gobinda, we synthesized a 16 lysine (K) residue-linked low-density lipoprotein receptor-related protein (LRP)-binding amino acid segment of apolipoprotein E (K16APoE). By mixing this protein with our designed therapeutic peptide HAYED, we successfully transported HAYED into an AD model mouse brain, and the peptide scavenged excess iron and radicals and decreased the necrosis of neurons, thus easing AD.

Coaxial electrospinning for encapsulation and controlled release of fragile water-soluble bioactive agents.

Coaxial electrospinning is a robust technique for one-step encapsulation of fragile, water-soluble bioactive agents, including growth factors, DNA and even living organisms, into core-shell nanofibers. The coaxial electrospinning process eliminates the damaging effects due to direct contact of the agents with organic solvents or harsh conditions during emulsification. The shell layer serves as a barrier to prevent the premature release of the water-soluble core contents. By varying the structure and composition of the nanofibers, it is possible to precisely modulate the release of the encapsulated agents. Promising work has been done with coaxially electrospun non-woven mats integrated with bioactive agents for use in tissue engineering, in local delivery and in wound healing, etc. This paper reviews the origins of the coaxial electrospinning method, its updated status and potential future developments for controlled release of the class of fragile, water-soluble bioactive agents.

Novel micelles from graft polyphosphazenes as potential anti-cancer drug delivery systems: drug encapsulation and in vitro evaluation.

In this study, a new class of amphiphilic methoxy-poly(ethylene glycol) grafted polyphosphazene with glycine ethyl ester side groups (PPP-g-PEG/GlyEt) was synthesized and characterized. An anti-cancer agent doxorubicin (DOX) was encapsulated into polymeric micelles derived from those copolymers, which exhibited considerably strong impact on micelle morphology: turned the rod-like and spherical drug free micelles into spheres and vesicles respectively. The in vitro release behavior of those drug-loaded micelles exhibits a sustained release manner and is affected by drug content. Cytotoxicity assay against adriamycin-resistant human breast cancer MCF-7 cell line showed that drug-loaded micelles based on PPP-g-PEG/GlyEt micelles can effectively suppress cell proliferation and the cytotoxicity was both time and concentration related, an enhanced cytotoxicity was observed either with increasing drug concentration or with prolonged incubation time. Moreover, flow cytometry results revealed a particle size dependency in cellular uptake of drug-loaded micelles. These findings suggest that the present copolymers can encapsulate water insoluble anti-cancer agents and contribute to improve drug sensitivity of adriamycin-resistant cell line.

A facile route for regioselective conjugation of organo-soluble polymers onto chitosan.

A facile route is described for the regioselective conjugation of organo-soluble polymers onto chitosan under very mild conditions, using SCC as intermediates. SCC could be prepared simply by mixing chitosan acidic aqueous solution with SDS. PEG or PCL were then grafted to SCC using the NHS/DCC coupling method. In addition, the polymers were found to be linked to chitosan through the hydroxyl groups of chitosan when stoichiometric SCC was used as a precursor. SDS could be removed simply by either precipitating the solution of SCC-graft-polymer in DMSO into Tris aqueous solution or dialyzing against Tris solution.

Encapsulation and controlled release of lysozyme from electrospun poly(epsilon-caprolactone)/poly(ethylene glycol) non-woven membranes by formation of lysozyme-oleate complexes.

In this study, the concept of hydrophobic ion pairing was adopted for incorporating lysozyme into electrospun poly(epsilon-caprolactone) (PCL)/poly(ethylene glycol) (PEG) non-woven membranes. The solubility of lysozyme in organic solvent was enhanced through the formation of lysozyme-oleate complexes, which could be directly loaded into PCL/PEG membranes using electrospinning technique. The resultant PCL/PEG nanofibers have a compact structure with an average diameter ranged from about 0.4 microm to 0.9 microm. The addition of PEG into the PCL nanofibers not only improved the hydrophilicity of the membrane, but also played an important role on in vitro lysozyme release rate. It was found that the release rate of lysozyme was enhanced with the increase of PEG content. In addition, the increase of salt concentration in the release medium accelerated lysozyme release. It has also been shown that the released lysozyme retained most of its enzymatic activity.

Versatile preparation of fluorescent particles based on polyphosphazenes: from micro- to nanoscale.

A series of intrinsically fluorescent hydrophobic and amphiphilic polyphosphazenes with ethyl tryptophan (EtTrp) and poly(N-isopropylacrylamide) (PNIPAAm) or poly(ethylene glycol) (PEG) as hydrophobic and hydrophilic segments, respectively, are synthesized. Depending on polymer composition and preparation procedure, particles with diameters ranging from micro- to nanoscale can be prepared successfully, which might be used as a visible tracer, both in vitro or in vivo, in drug- or gene-delivery systems, as well as in other biomedical studies such as diagnostic medicine and brain research. Most importantly, in combination with the flexible synthesis and versatile modification of polyphosphazene, this method provides a general protocol to engineer a broad range of fluorescent particles with different properties based on diverse polymers.

Fabrication and characterization of zein-based nanofibrous scaffolds by an electrospinning method.

Electrospun zein membranes were prepared using DMF as solvent. By changing the solution concentration, the electrospinning voltage and the distance between the spinneret and collector, nanofibrous meshes without bead defects could be obtained. In order to improve the mechanical strength of the hydrated zein meshes, core-shell-structured nanofibrous membranes with PCL as the core material and zein forming the shell were prepared by coaxial electrospinning. The core-shell structure of the composite fibers was confirmed by SEM characterization of the fibers, either extracted with chloroform to remove the inner PCL, or elongated to expose their cross-section. The composition and average diameter of the composite fibers could be modulated by the feed rate of the inner PCL solution. It was found that the core-shell fibrous membranes have similar wettability to the electrospun zein mesh. The presence of PCL in the fibers could significantly improve the mechanical properties of the zein membrane.

Biodegradable fibrous scaffolds composed of gelatin coated poly(epsilon-caprolactone) prepared by coaxial electrospinning.

A facile coaxial electrospinning technique was devised to prepare biodegradable core-shell fibrous scaffolds with poly(epsilon-caprolactone) (PCL) comprising the core structure and gelatin forming the coating of the fibers. The effect of the feed rate of the inner dope on the electrospinning process and fiber morphology was investigated. The results indicated that core-shell fibers with narrow size distribution and smooth surface morphology could be obtained when the feed rate was below 8 mL/h. An increase of the feed rate resulted in analogous increase in the diameters of both the inner PCL fiber core and the entire core-shell fibers. XPS analyses revealed that the surface of the core-shell fibers was tainted with a small amount of PCL. The outer gelatin layer in the core-shell fibers was crosslinked with glutaraldehyde. By optimizing the glutaraldehyde/gelatin feed ratio, crosslinked scaffolds with high porosity were obtained. The mechanic strength of the hydrated, crosslinked core-shell fibrous scaffolds was significantly enhanced because of the presence of hydrophobic PCL in the core region of the fibers. Results of cell culture studies suggested that the crosslinked, core-shell fibrous scaffold were nontoxic and capable of supporting fibroblast adhesion and proliferation.

Modulation of protein release from biodegradable core-shell structured fibers prepared by coaxial electrospinning.

Biodegradable core-shell structured fibers with poly(epsilon-caprolactone) as shell and bovine serum albumin (BSA)-containing dextran as core were prepared by coaxial electrospinning for incorporation and controlled release of proteins. BSA loading percent in the fibers and its release rate could be conveniently varied by the feed rate of the inner dope during electrospinning. With the increase in the feed rate of the inner dope, there was an associated increase in the loading percent and accelerated release of BSA. Poly(ethylene glycol) (PEG) was added to the shell section of the fibers to further finely modulate the release behavior of BSA. It was revealed that the release rate of BSA increased with the PEG percent in the shell section. By varying the feed rate of the inner dope and PEG content, most of BSA could be released from the core-shell structured fibers within the period of time ranging from 1 week to more than 1 month. The effect of the feed rate of the inner dope and addition of PEG into the shell section on the fiber morphology was also examined by scanning electron microscope.

Biodegradable hyaluronic acid/n-carboxyethyl chitosan/protein ternary complexes as implantable carriers for controlled protein release.

An ampholytic N-carboxyethyl chitosan (CEC), with various isoelectric points (IPs), was synthesized by grafting acrylic acid on chitosan utilizing Michael's reaction. Compared to native chitosan, CEC has enhanced water solubility and dramatically accelerated enzymatic degradation; the rate of degradation is proportional to the degree of substitution (DS). The results from turbidimetric titration and fluorescence studies revealed that CEC formed complexes with either hyaluronic acid (HA) or bovine serum albumin (BSA) within a certain pH range. The HA/CEC/BSA ternary complexes could be prepared by colloid titration with quantitative yield and BSA entrapment. The rate of BSA release from the complexes was affected by pH, ionic strength, DS of CEC, and the molecular weight (MW) of HA. The endurance of BSA release from the complexes could be extended up to 20 d by formulating them with high-MW HA and CEC with low DS.BSA release profiles from HA/CEC-2/BSA complexes.

A facile technique to prepare biodegradable coaxial electrospun nanofibers for controlled release of bioactive agents.

A one-step, mild procedure based on coaxial electrospinning was developed for incorporation and controlled release of two model proteins, BSA and lysozyme, from biodegradable core-shell nanofibers with PCL as shell and protein-containing PEG as core. The thickness of the core and shell could be adjusted by the feed rate of the inner dope, which in turn affected the release profiles of the incorporated proteins. It was revealed that the released lysozyme maintained its structure and bioactivity. The current method may find wide applications for controlled release of proteins and tissue engineering.

Novel copolyanhydrides combining strong inherent fluorescence and a wide range of biodegradability: synthesis, characterization and in vitro degradation.

In this work, a novel diacid monomer was synthesized in a very convenient scheme. The monomer is derived from naturally occurring products and emits strong fluorescence when polymerized to polyanhydride. The chemical structure of the monomer dCPS is as follows: HOC(O)ArOC(O)(CH2)2C(O)O--Ar--COOH. Copolyanhydrides composed of dCPS and sebacic acid were further prepared by melt copolycondensation, and characterized by IR, NMR, UV-Vis, DSC and fluorometry. The emission wavelength (lambda(em)) of the copolymers could be tuned by the excitation wavelength (lambda(ex)). Fluorescence intensity increased with the increase of dCPS content. The microspheres fabricated from the copolymer with dCPS content as low as 10% could be clearly visualized with fluorescence microscopy. Either blue or green images of the microspheres could be captured with an excitation of UV and visible light. The degradation rate of the copolyanhydrides decreased as the dCPS fraction increased, and the degradation duration could be modulated from several days to more than three months. In addition, it was found that the copolyanhydrides displayed surface degradation characteristics. In view of the advantages of the novel copolyanhydrides, such as easy preparation, unique inherent luminescent properties, and widely adjustable degradation rate, they might be useful for biomedical engineering.

[Tissue engineered bone reconstruction with modified PLGA/Type-I collagen compound scaffold].

OBJECTIVE: To fabricate bone grafts by bone marrow stromal cell combined with modified PLGA/Type-I collagen compound scaffold using tissue engineering method. METHODS: The modified PLGA/Type-I collagen compound scaffold was fabricated. The rabbit primary cultured osteoblasts were identified and seeded onto the modified compound scaffold for one week in vitro. The adhesion and growth of cells were observed with scanning electron microscope. The complex of cells and scaffold was implanted into the subcutaneous region of rabbits and new bone formation was evaluated. RESULTS: The rabbit bone marrow stromal cells were induced and differentiated into osteoblasts. The adhesion and growth of osteoblasts in cluster were observed on the surface of scaffolds. New bone formation was observed at one month postoperatively and active osteoblasts were found on the surface of the newly formed bone in vivo. CONCLUSION: The complex of PLGA and type-I collagen is an appropriate biodegradable scaffold and can be applied in bone tissue engineering.

[Effects of physical and chemical properties of polymeric nerve conduit on peripheral neuranagenesis].

OBJECTIVE: To evaluate the effects of degradation time and permeability of polymeric conduits on nerve regeneration. METHODS: After establishment of rat models with over 10 mm gap of sciatic nerve in right hind legs,four kinds of poly (ester, carbonate) nerve conduits was used to bridge the gaps and one group without conduit in gaps was used as control. The nerve regeneration and conduit degradation were examined both macroscopically and microscopically. The contraction of the muscle controlled by regenerated nerve was measured electrophysiologically at 4, 12 and 20 weeks after the operation. RESULT: Biodegradation time of nerve conduits in vivo was as fellows: 12 weeks in group A,4 weeks in group B and group C,and 20 weeks in group D,respectively. The histological quality of regenerative sciatic neurofibra in group A was the best among all groups (Mean rank 53.17, 38.83, 26. 60, 49.17 and 20.23,P<0.005), but the inflammatory reaction in group A was only less than that in group D and more than that in the other groups (Mean rank 45.87, 36.27, 34. 83, 51.63 and 21.4,P=0.001). The responsive rates of tibialis anterior muscle for electric stimulation in group A, B, C and D were 93.33%, 60%,20% and 73. 33%, respectively (P<0.005). CONCLUSION: Absorbable conduits with relatively good permeability and appropriate middle degrade time improve nerve regeneration and renovate function.

Controlled delivery system for norethindrone based on biodegradable poly-alpha,beta-(hydroxyalkyl)-DL-aspartamide.

The article describes the preparation of poly-(hydroxyalkyl)-DL-aspartamide (PHAA) by a (ring) opening reaction by hydroxyalkylamino; norethindrone (NET), as a model drug, was coupled to the polymers via hydroxyalkylamino spacers. PHAA and NETPHAA conjugates were characterized by FTIR, DSC, x-ray,(13)C NMR, and scanning electron microscopy and their structure were confirmed. The biocompatibility of PHAA was tested. The study showed that PHAA was a hydrophilic, nontoxic in vivo, nonantigenic material and had good biocompatibility as a drug carrier. The effect on drug release from the polymer of length of side chain, initial drug loading, and particle size of the polymer drug were investigated in tris-HCl buffer solution (pH 7.4, t = 37 degrees C). In vivo release in rabbits also was performed for 120 days. The experiment indicated that the concentration of NET in rabbits can be 1-2 microg/ml serum after 1 month; 10% of NET had been released from the polymer.