Polysuccinimide Research Articles

A new photocrosslinkable hydrogel based on a derivative of polyaspartic acid for the controlled release of ketoprofen

A novel photocrosslinkable and pH-sensitive hydrogel used for drug delivery was developed based on polyaspartic acid. Polysuccinimide (PSI) was modified by hydrazine and acryloyl chloride. The unreacted imide rings of PSI were hydrolyzed. Hydrogels were formed by photocrosslinking without any crosslinker or photoinitiator. Products were characterized by FT-IR and solid-state 13CNMR analysis. The swelling behaviors of hydrogel in various pH values were studied. Ketoprofen (KP) was chosen as a model drug. Two drug loading methods were compared. The release kinetics of KP was evaluated in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) at 37 °C. The results showed that drug-loaded hydrogels were resistant to SGF, and hence they could be useful for oral drug delivery. There would be a wide range of applications for controlled drug delivering system.

PEG-g-poly(aspartamide-co- N, N-dimethylethylenediamino aspartamide): Synthesis, characterization and its application as a drug delivery system

PEG-g-poly(aspartamide-co- N, N-dimethylethylenediamino aspartamide) (PEG-DMEDA-PASP) was synthesized by two-step ring-opening reactions of polysuccinimide (PSI) with α-methoxy-ω-amino-poly(ethylene glycol) and N, N-dimethylethylenediamine. The polymer structure was confirmed by 1H NMR and FT-IR. The resultant PEG-DMEDA-PASP with ammonium glycyrrhizinate (AMG) could form polymeric micelles in aqueous solution. The results of transmission electron microscopy (TEM) and dynamic light scattering (DLS) measurements revealed that these polymeric micelles were spherical particles with a narrow diameter distribution and that their average diameter was ca. 70 nm. These polymeric micelles had high-loading capacity (58%) and encapsulation efficiency (70%) for AMG. The results of in vitro release experiments showed that these polymeric micelles possessed sustained-release effects, with a release rate of 25% within 3 h and 90% within 24 h.

Polyaspartamide-Based Oligo-ethylenimine Brushes with High Buffer Capacity and Low Cytotoxicity for Highly Efficient Gene Delivery

Polyaspartamide-based oligo-ethylenimine brushes (PASP-EDA, PASP-TEPA, PASP-PEHA, and PASP-PEI 423) were synthesized from polysuccinimide (PSI) via a ring-opening reaction with N-Boc protected ethylenediamine, tetraethylenepentamine, pentaethylenehexamine, and linear polyethylenimine (Mn 423), respectively. PASP-TEPA, PASP-PEHA, and PASP-PEI 423 possess high buffer capacity between pH 5 and pH 7, which is comparable to that of branched PEI 25000. The cytotoxicity assay indicated that they all are less toxic than PEI 25000. At an N/P ratio of above 2, all of the four synthetic polycation brushes can condense plasmid DNA to form small sized (160-400 nm) polyelectrolyte complexes with positive surface charge. The transfection of HEK 293 cells with oligo-ethylenimine brush/pRE Luc polyplexes indicated that the transfection efficiencies increased with increasing the length of oligo-ethylenimine side chains. The luciferase expression with PASP-PEHA and PASP-PEI 423 were as high as or even a little higher than that of PEI 25000. The results demonstrate that polyaspartamide-based oligo-ethylenimine brushes are a very promising class of novel polycations for highly efficient and less toxic gene delivery.

Kinetic analysis of solid-phase polycondensation of aspartic acid

327 Polycondensation of amino acids is the subject of a multitude of studies. Compounds of this class are important both for chemical engineering, e.g., production of polyamides, and for chemical science, in particular, for biochemistry. In this study, L -aspartic acid (ASP) was chosen. Its polycondensation has been studied in detail [1]. However, the main body of relevant studies is limited to considering various polycondensation methods and the effect of reaction conditions on the composition and properties of reaction products [2]. The conclusions about the reaction mechanism are drawn from the results of such studies. Kinetics, which is an important tool for establishing the mechanism of complex processes, is modestly represented. Only rather recently did measurements of ASP weight loss during dynamic thermogravimetric analysis (TGA) [3] show two peaks in the weight loss vs. temperature curve obtained by differentiation. It was suggested that this is a consequence of the two-step character of the process: first, polyaspartic acid is formed, and then it is dehydrated to give polysuccinimide (PSI).

Swelling properties of aspartic acid-based hydrogels

Chemically crosslinked poly(aspartic acid) (PASP) gels were prepared by the hydrolysis of polysuccinimide (PSI). This latter was prepared by thermal polycondensation of aspartic acid. The PSI chains were crosslinked by 1,4-diaminobutane. The consecutive reactions of hydrolysis and swelling kinetics of PSI- and PASP-based gels were studied at different pH values. Two distinct swelling mechanisms were proposed. The cooperative diffusion coefficient has been found to be three orders of magnitude higher in pH 14 solution than at pH 8.

Synthesis and characterization of superabsorbent hydrogels composites based on polysuccinimide

AbstractA kind of novel superabsorbent hydrogel with high swelling ratio property that could be used for the development of water absorbing resin, soil water retention agent, and chemical sand‐fixing material was synthesized in this study. The hydrogels were prepared by the crosslinking reaction of polysuccinimide (PSI). The relationships between swelling ratio and volume of solvent as well as the concentration of crosslinking agent were investigated in detail. Several composites, such as starch, carrageenan, and polyacrylamide, were added into hydrogels to enhance the swelling ratio. It was found that the swelling ratio was significantly increased, which the maximum water absorbency was enhanced 2.46 times when the composite polyacrylamide (PAM) was added compared to the control. The effects of ionic strength and sensitivity of pH on hydrogels were also studied. The modified hydrogels products with swelling ratio less sensitivity to the salinity as well as relative high swelling ration in salinity system were also obtained by adding PAM. Through the Fourier transform infrared spectroscopy (FTIR) characterizations, the crosslinking reaction mechanism and the structure of composite were proposed. In addition, the transmission electron microscopy (TEM) examinations showed that some composite materials elevated the physical crosslinked and connected channels density substantially. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 102: 550–557, 2006

Diethylenetriaminepentaacetic Acid−Gadolinium (DTPA-Gd)-Conjugated Polysuccinimide Derivatives as Magnetic Resonance Imaging Contrast Agents

Biocompatible polysuccinimide (PSI) derivatives conjugated with diethylenetriaminepentaacetic acid gadolinium (DTPA-Gd) were prepared as magnetic resonance imaging (MRI) contrast agents. In this study, we synthesized PSI derivatives incorporating methoxy-poly(ethylene glycol) (mPEG) as hydrophilic ligand, hexadecylamine as hydrophobic ligand, and DTPA-Gd as contrast agent. PSI was synthesized by the polycondensation polymerization of aspartic acid. All the synthesized materials were characterized by proton nuclear magnetic resonance (1H NMR). Critical micellization concentrations were determined using fluorescent probes (pyrene). Micelle size and shape were measured by electro-photometer light scattering (ELS) and atomic force microscopy (AFM). The formed micelle size ranged from 100 to 300 nm. The T1-weighted MR images of the phantom prepared with PSI-mPEG-C16-(DTPA-Gd) were obtained in a 3.0 T clinical MR imager, and the conjugates showed a great potential as MRI contrast agents.

Preparation and Properties of Novel Biodegradable Hydrogel based on Cationic Polyaspartamide Derivative

Novel copolymers consisting of poly(2-hydroxyethyl aspartamide-co-N,N'-dimethyl-1,3-propane aspartamide) (PHEA-DPA) were prepared from polysuccinimide (PSI), which is the thermal polycondensation product of aspartic acid, via a ring-opening reaction with N,N'-dimethyl-1,3-propane diamine (DPA) and ethanolamine. The prepared water-soluble copolymer was then crosslinked by reacting it with hexamethylene diisocyanate to provide the corresponding gel. The swelling behavior and morphology of the crosslinked hydrogels were investigated. The degree of swelling decreased with increasing crosslinking reagent due to the higher crosslinking density. It was also confirmed that the swelling property is affected by pH. At low pH (< pH 4), swelling is increased due to the ionization of DPA with a tertiary amine moiety. In addition, a reversible swelling and de-swelling behavior was demonstrated by adjusting the pH of the solution. The prepared hydrogels showed a well-interconnected microporous structure with regular 5-20 <TEX>$\mu$</TEX>m sized pores.

Preparation and Water Absorbent Behavior of Superabsorbent Polyaspartic Acid Resin

Superabsorbent polyaspartic acid (PASP) resin was prepared from high molecular weight polysuccinimide (PSI), which was synthesized from l-aspartic acid by thermal polycondensation. The effects of the reaction temperature, the reaction time, the concentration of the solvent, the molecular weight of PSI, the concentration of the cross-linking agent, the hydrolysis conditions, and the drying temperature on the swelling ratio of PASP resin were investigated. The swelling ratios of PASP resin in deionized water and saline solution were measured, and the biodegradability of PASP hydrogel was evaluated. The results show that the swelling ratios of PASP resin in deionized water were 100–1,120 g/g depending on the preparation conditions. The swelling ratio of PASP resin in saline solution reached 143 g/g, and PASP resin was a kind of biodegradable material with high water absorbency, so this PASP resin can be used as agricultural and horticultural water-holding material, and in manufacturing of diapers, sanitary napkins, medical products, etc.

Nano aggregates of biodegradable amphiphilic poly(hydroxyethyl aspartamide- co-propyl aspartamide) grafted with poly( d, l-lactide)

Amphiphilic graft copolymers composed of poly(hydroxyethyl aspartamide)- co-propyl aspartamide) (PHEA-PA) as the hydrophilic backbone and poly(lactide) (PLA) as the hydrophobic side chain were successfully synthesized by grafting lactide (LTD) onto PHEA-PA. Polysuccinimide (PSI) was firstly synthesized from l-aspartic acid through thermal condensation polymerization method, and then followed by two-step aminolysis processes to form PHEA-PA with different amounts of hydroxyl groups. The hydroxyl groups were then used as initial points to graft PLA onto PHEA-PA backbone via a ring-opening polymerization in the presence of Sn(Oct) 2. The grafting reaction of PLA onto PHEA-PA was confirmed by 1H NMR, FT-IR, and DSC. Micelle-like aggregates were obtained when the amphiphilic comb-like copolymer solution of DMF was added into an excessive amount of water. Strong hydrophobic intramolecular and intermolecular association of PLA chains led to aggregates with hydrophobic microdomains. The dispersion of the self-aggregates of poly(hydroxyethyl aspartamide- co-propyl aspartamide)- g-poly( d, l-lactide) (PHEA-PA- g-PLA) copolymers is stable in aqueous medium. Spherical aggregates of PHEA-PA- g-PLA were observed by transmission electron microscopy (TEM) and scanning electron microscopy (SEM), the diameters were about 100 nm.

Superabsorbent hydrogels from poly(aspartic acid) with salt-, temperature- and pH-responsiveness properties

Polyaspartic acid (PAsp) resin was synthesized by polysuccinimide (PSI), through chemical cross-linking using the cross-linking agent (diamine). The effects of reaction variables, such as PSI concentration and terminal pH on the water absorbent capacity have been studied. These phenomena were discussed according to structural parameters, which were confirmed by SEM. Water absorbencies were compared for the hydrogels at terminal pH 8 and 10. The water absorbent capacity enhanced with increasing terminal pH and decreasing PSI concentration. The swelling/deswelling kinetics of the super-absorbent hydrogels was investigated as well. It is found that the hydrogels showed ampholytic and reversible pH-responsiveness properties. The variational water absorbencies were attributed to swelling theory based on the hydrogel physical and chemical structure. The swelling was also extremely sensitive to the temperature, ionic strength and cationic kind. The reversible pH-responsiveness, salt- and temperature-sensitivity of the hydrogels make this intelligentized polymer had wider applications.

Aggregation of biodegradable amphiphilic poly(succinimide- co- N-propyl aspartamide) and poly( N-dodecyl aspartamide- co- N-propyl aspartamide) in aqueous medium and its preliminary drug-released properties

Two series of biodegradable amphiphilic copolymers, poly(succinimide- co- N-propyl aspartamide) (PSI-PA) and poly( N-dodecyl aspartamide- co- N-propyl aspartamide) (PDDA-PA) were synthesized by partial and total aminolysis of polysuccinimide (PSI), respectively. PSI-PA copolymers could self-aggregate in water directly under ultrasonication at room temperature. Differing from PSI-PA copolymers, the aggregates of PDDA-PA need to add PDDA-PA DMF solution into an excessive amount of water. The aggregative properties of PSI-PA and PDDA-PA copolymers have been investigated by dynamic light scattering (DLS) and surface tension measurements. Hydrophilicity of these two copolymers was attributed to the N-propyl aspartamide segments. Due to the stiff structure, succinimide segments preferred to form irregular hydrophobic microdomains, and some aggregates of PSI-PA are bimodal size distribution in water medium, while the more flexible PDDA-PA copolymer chains preferred to form monodispersed spherical aggregates. Elevated temperature could reduce the aggregate size of both PSI-PA and PDDA-PA copolymers due to the breaking of the hydrogen bonding and the releasing of the bonded water molecules. PSI-PA copolymers were surface active, while the surface tension of PDDA-PA copolymers was independent on concentration. The drug-loaded aggregates of PSI-PA also have been prepared and the preliminary release properties have been studied in vitro.

Amphiphilic Hexylamine Modified Polysuccinimide: Synthesis, Characterization, and Formation of Nanoparticles in Aqueous Medium

A series of hexylamine modified polysuccinimide (PSI–HA) copolymers were synthesized by aminolysis of polysuccinimide (PSI) with hexylamine. FTIR and 1H NMR measurements confirmed the structure of the copolymers and the substitution degree of the N-hexyl aspartamide units ranged from 7 to 92 mol%. Stable nanoparticles formed when the DMF solution of PSI–HA copolymers was dropped into excess water, and the particle size reduced as increasing the substitution degree. 1H NMR analysis indicated that hexyl chain and succinimide units interacted to form the hydrophobic core, while, the nanoparticles were stabilized by the amide groups which formed hydrogen bonds with the surrounding water molecules. The nanoparticles became more compact at higher temperature due to the break of hydrogen bonds between amide groups and water molecules. Dynamic light scattering (DLS) and scanning electron microscopy (SEM) results showed that the nanoparticles were nearly spherical. Larger nanoparticles formed when the dispersion concentration increased from 0.1% to 1.0% according to the DLS and steady-state fluorescence measurements. After the nanoparticles formed in water, a sequential dilution can't influence the particles size of the nanoparticles any longer.

Poly-?,?-(3-hydroxypropyl)-DL-aspartamide: A new drug carrier

Poly-α,β-(3-hydroxypropyl)-DL-aspartamide (PHPA) was synthesized by the ring-open reaction of polysuccinimide (PSI) and 3-hydroxypropylamine. The polymer was characterized by 1H-NMR, 13C-NMR, FTIR, and GPC. Mark–Houwink coefficients were obtained from viscometry and GPC measurements, K = 5.53 × 10−3 and α = 0.78 in water. The acute toxicity of PHPA was examined and it revealed no death in ICR mice up to the dose treated of 15.3 kg/kg, and hematological parameters showed no significant difference between treated and control animals. The potential use of PHPA as a drug carrier was also investigated. In a typical case, a contraceptive drug, norethindrone (NET), was bonded to PHPA, and the drug sustained released as long as 120 days an in vitro test. © 2000 John Wiley & Sons, Inc. J Appl Polym Sci 77: 2411–2417, 2000

A new water-soluble synthetic polymer, α,β-polyasparthydrazide, as potential plasma expander and drug carrier

The reaction between a polysuccinimide (PSI) and hydrazine produces a water-soluble polymer α,β-polyasparthydrazide (PAHy). Tests of the polymer on laboratory animals established its potential use as a plasma substitute. Acute toxicity studies revealed no death in the animals treated, and subacute toxicity studies recorded no notable difference between treated and control animals either in terms of body-weight or the principle haematological parameters. Haemodynamic studies likewise established no significant variation in systolic and diastolic pressure or in heart beat between the two groups. Solutions of PAHy administered to bled animals improved the lowering of blood values caused by the bleeding. Moreover, PAHy was not capable of inducing any immune response when administered intradermally to laboratory animals. The potential use of PAHy as a drug carrier was also investigated. PAHy was bonded with a model drug, the antibacterial Ofloxacin, by means of a water-soluble carbodiimide, . N-ethyl-[ N′(3-dimethyl-aminopropyl) carbodiimide hydrochloride (EDC). The resulting conjugate, PAHy-Ofloxacin is, like the polymeric carrier, water-soluble and contains a quantity of linked drug equivalent to 9% (w/w).

Properties and reactivity of polysuccinimide

AbstractA simple method has been suggested for the fractionation of polysuccinimide (PSI); the intrinsic viscosities of fractions were measured and the parameters of the Mark‐Houwink equation were determined. The possibilities of reactions of PSI with primary amines such as histamine, tyramine, tryptamine, mono‐BOC‐ethylenediamine, glycine nitroanilide, and ethanolamine were checked; the reaction rate constants and the effect of some catalysts were determined.