Poly-amino-acid is one of the polymers with good biocompatibility. It has a special use in the field of controlled release drug.In this article are reviewed the types, modification,dosage forms,structure and biocompatility of poly-amino-acid.

For the purpose of increasing the hydrophilicity of poly aspartic acid, a series of polymer of L-aspartic acid and 4-aminobutanoic acid with different ratios (mol/mol) were prepared. The copolymers were characterized by 13CNMR, DSC and x-ray. The confirmed the structures of the polymers. In-vitro tests of release at phosphate buffer saline, enzyme solution of trypsin and papain (37.0 degrees C, pH = 7.4) were carried out. The result indicated that the polymers could be degraded in some degree, and that 4-aminobutanoic acid segments accelerated the degradation rate of the polymers. Skin irritation test and systemic acute toxicity test were carried out, which showed that the polymer was a nontoxic biomedical material.
Animals ; Aspartic Acid ; chemistry ; Female ; Hydrolysis ; Male ; Materials Testing ; Mice ; Polymers ; chemical synthesis ; chemistry ; metabolism ; toxicity ; Rabbits ; gamma-Aminobutyric Acid ; chemistry

Objective:To prepare and characterize cyclodextrin inclusion complexes of regorafenib and to investigated their antitumor effects.Methods:Three inclusion complexes (RG-β-CD,RG-γ-CD,RG-Hp-β-CD) were prepared by recrystallization and solvent evaporation methods between regorafenib (RG) and β-cyclodextrin (β-CD),γ-cyclodextrin (γ-CD) and hydroxypropyl-β-cyclodextrin (Hp-β-CD),respectively.The compounds were characterized by Fourier transform infrared spectroscopy (FT-IR),thermogravimetric analysis (TG),differential scanning calorimetry (DSC),powder X-ray diffraction (PXRD),1 H nuclear magnetic resonance (1H-NMR),nuclear overhauser effect spectroscopy (NOESY).Human colon cancer SW620 cells were inoculated to Balb/c-nu nude mice,PBS,RG or RG-β-CD were given orally for 3 weeks,and the volumes of tumor were determined and compared among 3 groups.Results:The solubility and dissolution were improved after inclusion with 3 kinds of cyclodextrins.RG-β-CD had the best stability,followed by RG-γ-CD inclusion.The in vivo study showed that the tumor suppressive effect of RG-β-CD was stronger than that of regorafenib.Conclusion:The bioavailability of regorafenib by inclusion with cyclodextrin is enhanced due to the increased solubility,which can provide an effective method for improving solubility and dissolution of antitumor agents.

A series of Poly[aspartic acid-co-L-lysine](PAL) are copolycondensed by DL-aspartice acid and L-lysine with different ratios. Their constructions are identified by the spectra of 1H-NMR, FT-IR, X-Ray). These spectra are proved to have good regularity of these copolymers. alpha,beta-Poly[(N-hydroxypropyl/aminoethyl)-DL-Aspartamide-co-L-lysine] (PHAAL) is synthesized by ring-opening poly [aspartic acid-co-lysine] (PAL). PHAAL has good degradability in the phosphoric acid buffer solution (0.01 M, pH = 7.4) in the enzyme solution (Papain, Trypsine). PHAAL appeared tobe low cytotoxicity in Hela, ECV-304, Bcap37 cell lines, which was quantified by MTT assay. The combination ability of PHAAL with plasmid DNA was evaluated by agarose gel electrophoresis with agarose gel (1.0% w/v) containing ethidium bromide (0.25 microg/ml). The PHAAL with higher ratios of lysine in the copolymers have higher ability of condensing DNA. In summary, PHAAL, the polyaminoacid materials, could be one kind of macromolecule materials tobeused as the non-viral gene vehicle.
Aspartic Acid ; chemical synthesis ; chemistry ; toxicity ; Biopolymers ; chemistry ; toxicity ; Endothelial Cells ; cytology ; Gene Transfer Techniques ; Genetic Therapy ; methods ; Genetic Vectors ; chemical synthesis ; chemistry ; toxicity ; HeLa Cells ; Humans ; Materials Testing ; Umbilical Cord ; cytology

Objective:To study the characteristics and stability of new (S)-pantoprazole sodium hydrates.Methods:The X-ray single crystal diffractometer (SXRD),X-ray powder diffractometer (PXRD),thermogravimetric analysis (TG) and infrared spectrometry (IR) were used to characterize (S)-pantoprazole sodium hydrates.The stability of the hydrates was evaluated by high temperature test,affecting factors test and accelerated test.Results:The crystalline water in (S)-pantoprazole sodium hydrates were very easy to lose and obtain,but crystal structure was not changed significantly.The transition from (S)-pantoprazole sodium trihydrate to (S)-pantoprazole sodium hemipentahydrate occurred at approximately 40 ℃ and reversible transitions from hemipentahydrate to trihydrate occurred at high humidity.Two hydrates had no significant difference in accelerated test.Conclusion:The crystal structure of the two hydrates are almost the same,and hemipentahydrate is more stable than trihydrates at high temperature or at exposure to light[at (4500 ± 500)lx].

Objective:To prepare a nano-carrier based on combining bacterial outer membrane vesicles (OMV) with three block polymer pluronic F127 (PEO100-PPOss-PEO100) (OMV-F127) and to investigate its immunological activity.Methods:Attenuated salmonella (sal) was cultivated.OMV were separated by centrifugal ultrafiltration or ultrasonication,and OMV-F127 was prepared by mechanical extrudation method.The protein contents and compositions were tested with BCA and SDS-PAGE;the morphology of OMV,F127 and OMV-F127 were observed with FM and TEM;the particle sizes and their zeta potential were determined with DLS.Mouse macrophage RAW246.7 cells were treated with OMV-F127 (50 μg/mL,100 μg/mL) In vitro,and the concentrations of IL-12,TNF-α and IFN-γin culture supernatant were measured with ELISA kits.Results:The contents of protein in separated OMV by centrifugal ultrafiltration and ultrasonication were 2.8 mg/mL and 2.7 mg/mL,respectively.SDS-PAGE showed the marker protein OmpF/C in OMV.Under the FM and TEM,ball-like structure of F127 and OMV-F127 was observed.Size analysis revealed that the diameters of OMV,F127 and OMV-F127 were (72 ±2)nm,(90 ± 3)nm and (92 ± 2)nm,respectively.ELISA tests revealed that OMV-F127 significantly stimulated the secretion of IL-12,TNF-α and IFN-γ in RAW246.7 cells.Conclusion:A nano-carrier based on bacterial OMV has been prepared,which can stimulate the secretion of cytokines and may have immunomodulatory effects.

Objective:To design and synthesize photosensitizers with different substituents and to identify its physicochemical characteritics and photodynamic effect on tumor cells.Methods:Two kinds of BODIPY photosensitizers BPOI and BPCI were synthesized through condensation reaction between aldehyde and reactive hydrogen of pyrrole,followed with electrophilic substitution reaction.Physicochemical properties were characterized by 1H NMR,FT-IR and UV-visible absorption spectra and fluorescence emission spectra.The ability to produce reactive oxygen species was detected by BPDF and DCFH-DA.Photodynamic therapy effect on rat glioma C6 cells in vitro was determined by MTT method.Results:Two kinds of BODIPY photosensitizers BPOI and BPCI were successfully synthesized with different substituents,which were confirmed by 1H NMR,FT-IR.Both materials had low toxicity and could be readily taken up by tumor cells.The ability of synthesized photosensitizers to produce reactive oxygen species was strongly influenced by solvent polarity when the substituent belongs to electron-donating group,while no effect was found when the substituent belongs to electron-withdrawing group.Conclusion:Photosensitizer BPOI with electron-donating substituent produces reactive oxygen species with a slow rate in a highly polar environment,while the ability to produce reactive oxgen is greatly improved in a low polarity environment,which is expected to be used for environmental-selective photodynamic therapy in tumor cells.

Objective:To synthesize 5-fluorouracil-nicotinamide (5-FU-NCT) cocrystal and to investigate its physicochemical and biological properties.Methods:The cocrystal of 5-Fu-NCT was prepared through the cooling technology.PXRD,NMR,FTIR and DSC were used to characterize the structure of 5-FU-NCT cocrystal.Solubility was measured by HPLC method.Drug resistant human liver cancer BEL-7402/5-FU cells were treated with 5-FU-NCT cocrystal,the inhibition effect was tested by MTT and HE staining,and cancer cell migration was determined by scratch test.Results:According to PXRD,NMR,FTIR and DSC results,the cocrystal of 5-Fu-NCT had been synthesized successfully.The characteristic diffraction peaks (2θ/°) of the cocrystal were 16.4,20.4,22.3,27.9 and 30.1.The solubility of 5-FU-NCT was 13.5 g/L as measured by HPLC.The antitumor activity tests showed that 5-FU-NCT cocrystal enhanced anticancer effect of 5-FU,and the IC50 of 5-FU and 5-FU-NCT was 129.6 μg/mL and 42.6 μg/mL,respectively.Conclusion:5-Fu-NCT cocrystal have been synthesized successfully through the cooling technology and it shows a more enhanced anticancer effect in comparison to 5-FU on BEL-7402/5-FU cells.

Tumor tissues are composed of tumor cells and complicate microenvironment. Tumor associated macrophages (TAMs) as an important component in tumor microenvironment, play fundamental roles in tumor progression, metastasis and microenvironment regulation. Recently, studies have found that nanotechnology, as an emerging platform, provides unique potential for cancer imaging and therapy. With the nanotechnology, TAMs imaging presents direct evidence for cancer development, progression, and the effectiveness of cancer treatments; it also can regulate the immunosuppression of tumor microenvironment and improve therapeutic efficiency through TAMs targeted killing or phenotypic transformation. In this article, we illustrate the function of TAMs and review the latest development in nano-carriers and their applications in tumor associated macrophage targeting cancer imaging and therapy.

In order to improve the drug's solubility, dissolution and bioavailability, RG-β-CD, RG-γ-CD and RG-Hp-β-CD were prepared by co-crystallization between Regorafenib (RG) and β-cyclodextrin (β-CD), γ-cyclodextrin (γ-CD) and Hydroxypropyl-β-cyclodextrin (Hp-β-CD).Three inclusion complexes were prepared by recrystallization and solvent evaporation methods and characterized by fourier transform infrared spectroscopy (FT-IR), thermal analysis (TG), differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD),H nuclear magnetic resonance (H-NMR), nuclear overhauser effect spectroscopy (NOESY).experiments, tumor suppression assay were made with SW620 colon cancer cell.The ability of solubility and dissolution were improved after inclusion with three kinds of cyclodextrins. The regorafenib-β-cyclodextrin inclusionis proved to have the best stability. The less enhanced was regorafenib-γ-cycl-odextrin inclusion. The best dissolution of regorafenib-β-cyclodextrin inclusion complex was to bring as the tumor suppression assay, the result shows that regorafenib inclusion with β-cyclodextrin is better than regorafenib itself.The bioavailability of regorafenib by inclusion with cyclodextrin can enhance due to the solubility enhancement of RG, which can provide an effective method for improving solubility and dissolution of insoluble drug in clinical medication.