Biodegradable Amphiphilic Poly Research Articles

Synthesis of a New Poly(ε-caprolactone)-g-Chitosan Amphiphilic Graft Copolymer with a "Reverse" Structure.

Hydrophilic chitosan (CHT) and hydrophobic polyε-caprolactone (PCL) are well-known biocompatible and biodegradable polymers that have many applications in the biomedical and pharmaceutical fields. But the mixtures of these two compounds are considered incompatible, which makes them not very interesting. To avoid this problem and to further extend the properties of these homopolymers, the synthesis of a new graft copolymer, the fully biodegradable amphiphilic poly(ε-caprolactone-g-chitosan) (PCL-g-CHT) is described, with an unusual "reverse" structure formed by a PCL backbone with CHT grafts, unlike the "classic" CHT-g-PCL structure with a CHT main chain and PCL grafts. This copolymer is prepared via a copper-catalyzed 1,3-dipolar Huisgen cycloaddition between propargylated PCL (PCL-yne) and a new azido-chitosan (CHT-N3 ). In order to obtain an amphiphilic copolymer regardless of the pH, chitosan oligomers, soluble at any pH, are prepared and used. The amphiphilic PCL-g-CHT copolymer spontaneously self-assembles in water into nanomicelles that may incorporate hydrophobic drugs to give novel drug delivery systems.

Effect of stereocomplex formation between enantiomeric poly(l,l-lactide) and poly(d,d-lactide) blocks on self-organization of amphiphilic poly(lactide)-block-poly(ethylene oxide) copolymers in dilute aqueous solution

The effect of crystallization of a hydrophobic poly(lactide) block on the self-organization of biocompatible and biodegradable amphiphilic poly(lactide)-block-poly(ethylene oxide) (PLA-b-PEO) copolymers in a dilute aqueous solution has been investigated. It was demonstrated that the co-crystallization of poly(L,L-lactide) [P(L,L)LA] and poly(d,d-lactide) [P(d,d)LA] chains under equimolar mixing of P(L,L)LA46-b-PEO113 and P(d,d)LA56-b-PEO113 copolymers resulted in the formation of stable and spontaneously water-redispersible stereocomplex micelles with semicrystalline P(L,L)LA/P(d,d)LA cores. It was shown that the P(L,L)LA46 / P(d,d)LA56-b-PEO113 stereo-complex micelles produced by dialysis can be potential vehicles for the anticancer agent oxaliplatin

A biodegradable amphiphilic poly(aminoester) dendrimer for safe and effective siRNA delivery.

Small interfering RNA (siRNA)-based therapeutics represent a novel and compelling drug modality, provided that safe and competent vectors are available for their delivery. Here, we report a biodegradable amphiphilic poly(aminoester) dendrimer for effective siRNA delivery. This dendrimer is readily biodegradable upon enzyme action, and harnesses the delivery features of both lipid and polymer vectors thanks to its lipid/dendrimer hybrid structure. This study opens new perspectives for developing biodegradable and biocompatible vectors for siRNA therapeutics.

Novel class of nanofiber hydrogels based on the biodegradable amphiphilic copolymers poly(sarcosine) and poly(l-lactic acid) and prepared using alcohols

Route of preparation can be an important step in producing safe and effective controlled-release drug vehicles. We now describe a novel class of hydrogels based on biodegradable amphiphilic polymers consisting of hydrophobic poly(l-lactic acid) and hydrophilic poly(sarcosine). The hydrogels were prepared by initially dissolving the polymers in methanol, ethanol, and butanol, which are also amphiphilic. Transmission electron microscopy revealed that the hydrogels consist of self-assembled nanofibers, with a dynamic modulus greater than the loss elastic modulus over a range of stress cycles at different frequencies. Differential scanning calorimetry indicated that the hydrogels contain stable poly(l-lactic acid) crystals. Importantly, the hydrogels did not elicit irritation in a 3D model of the human corneal epithelia, and suppressed, by more than 20%, the initial drug burst typically associated with controlled-release vehicles already on the market. Hence, the hydrogels show promise as a new class of controlled-release drug delivery systems.

Self-Assembled, Biodegradable Magnetic Resonance Imaging Agents: Organic Radical-Functionalized Diblock Copolymers.

We report the design, synthesis, and evaluation of biodegradable amphiphilic poly(ethylene glycol)-b-polycarbonate-based diblock copolymers containing pendant persistent organic radicals (e.g., PROXYL). These paramagnetic radical-functionalized polymers self-assemble into micellar nanoparticles in aqueous media, which preferentially accumulate in tumor tissue via the enhanced permeability and retention (EPR) effect. Through T1 relaxation NMR studies, as well as magnetic resonance imaging (MRI) studies on mice, we show that these nanomaterials are effective as metal-free, biodegradable MRI contrast agents. We also demonstrate anticancer drugs can be readily loaded into the nanoparticles, conferring therapeutic delivery properties in addition to their imaging properties making these materials potential theranostic agents in the treatment of cancer.

Polyanhydride micelles with diverse morphologies for shape-regulated cellular internalization and blood circulation.

Biodegradable amphiphilic poly (ethylene glycol) (PEG) based ether-anhydride terpolymer, consisting of PEG, 1, 3-bis (p-carboxyphenoxy) propane (CPP) and sebacic acid (SA), namely PEG-CPP-SA terpolymer, was employed to self-assemble into micelles by adding water into a solution of the terpolymer in tetrahydrofuran (THF). The shape of polyanhydride micelles can be regulated by simply adjusting the water addition rate, where spherical, rod-like and comb-like micelles can obtained under water addition rate of 20, 3 and 1 ml/h, respectively. The effect of micellar morphologies on the cellular internalization and intracellular distribution were characterized qualitatively with cervical cancer cells (HeLa cells) and hepatoma cells (HepG2 cells) by fluorescence microscopy, confocal laser scanning microscopy (CLSM), flow cytometry (FCM) and transmission electron microscopy (TEM). The results reveal that the cellular uptake of micelles are micelle-shape-dependent (rod-like micelles may possess the highest cellular internalization rate) and cell-type-specific. Each endocytic pathway can make a contribution to this process in different degree. Moreover, blood circulation experiments of these micelles were carried out, demonstrating that comb-like micelles have a relatively longer blood circulating feature, which may due to its irregular shape help to increase the sensitivity to fluid forces and allows them to tumble and align with the blood flow.

A synergy effect between the hydrophilic PEG and rapid solvent evaporation induced formation of tunable porous microspheres from a triblock copolymer

A uniform Evansblue-loaded biodegradable amphiphilic poly(lactide-co-glycolide-b-ethylene glycol-b-lactide-co-glycolide)(PLGE) porous microsphere prepared by a synergy effect between the hydrophilic PEG and rapid solvent evaporation is reported. Our approach is based on the double emulsion (W/O/W) in which solvent evaporates rapidly. We show the introduction of hydrophilic PEG and rapid solvent evaporation play an important role in the formation of biodegradable porous microspheres. The microsphere size, pore size and distribution as well as drug loading efficiency can be well controlled by varying the polymer compositions. Meanwhile, the drug release behaviors of PLGE porous microspheres are also discussed.

Multiblock Polyurethanes Based on Biodegradable Amphiphilic Poly(ε-caprolactone)/ Poly(ethylene glycol) Segments as Candidates for Tissue Engineering Applications

Biodegradable amphiphilic multiblock poly(ether-ester-urethane)s were prepared by one-step bulk polycondensation of PEG and PCL macrodiols and HMDI with good yields and high molecular weights. The copolymers were characterized by 1 H-NMR, FT-IR, SEC, TGA and DSC analysis. Different ratios of PEG/PCL, PEG macromonomer length and copolymer molecular weights allowed for tuning their hydrophilicity. Thanks to their tunable characteristics, the prepared multiblock copolymers can be exploited in the fabrication of biodegradable scaffolds for tissue engineering by means of the electrospinning technique.

Tunable Amphiphilic Poly(Ether‐Anhydride) Gel Nanoparticles for the Delivery of Hydrophobic Drugs

AbstractSummary: Biodegradable amphiphilic poly(ether‐anhydride) gel nanoparticles (GNPs) with a hydrophobic crosslinked core and a hydrophilic PEG shell have been prepared from amphiphilic photo‐crosslinkable ether‐anhydride macromers via microemulsion photo‐polymerization. The properties of the GNPs, such as degradability, size and drug‐loading capacity, were investigated by tailoring the length of PEG chains in macromers from 400 to 4000 and by the addition of a hydrophobic photo‐crosslinkable monomer: stearic monoacrylic anhydride (MSA). TEM showed that the GNPs were spherical in shape with a core‐shell structure when MSA was added. The GNPs were used as the carriers to enhance the solubility of hydrophobic drugs. Indomethacin (IND) as a model drug was entrapped in the hydrophobic crosslinked core by an in situ embedding method. Results showed that IND maintained chemically intact during the formulation process, and its dissolution rate were improved compared to those of the pure IND. The GNPs prepared from PEG macromer (molecular weight: 4000) with the addition of MSA exhibited the zero‐order release behavior, which is potentially useful to control the release of hydrophobic drugs.

Synthesis and characterization of biodegradable amphiphilic PEG-grafted poly(DTC- co-CL)

A novel biodegradable copolymer, poly(5,5-dibromomethyltrimethylene carbonate- co-ɛ-caprolactone) (poly(DBTC- co-CL)) with pendant bromine groups, was synthesized via ring-opening polymerization (ROP) of ɛ-caprolactone (CL) and 5,5-dibromomethyltrimethylene carbonate (DBTC) using stannous octoate (Sn(Oct) 2) as catalyst. Then the pendant bromine groups were completely converted into azide form, which permitted “click” reaction with alkyne-terminated polyethylene (A-PEG) by Huisgen 1,3-dipolar cycloadditions preparing biodegradable amphiphilic poly(DTC- co-CL)- g-PEG graft copolymer. The graft copolymer was characterized by nuclear magnetic resonance (NMR) and size-exclusion chromatography (SEC).

Hydrolytic and microbial degradation of multi-block polyurethanes based on poly(ɛ-caprolactone)/poly(ethylene glycol) segments

Biodegradable amphiphilic multi-block poly(ether-ester-urethane)s were prepared by one-step bulk polycondensation of PEG and PCL macro-diols and HMDI. For biomedical or environmental applications of the proposed materials, one of the critical steps is the study of the degradation characteristics under physiological or environmental conditions. Different ratios of PEG/PCL and molecular weights of the resultant copolymers allowed for tuning their hydrophilicity, as evaluated by water uptake measurements. The swelling results were further supported by microgravimetric measurements performed by QCM-D. In vitro hydrolytic biodegradation was carried out under different conditions ( i.e., in phosphate buffer solution – with and without Lipase). Total mineralization in the presence of microorganisms from a sample of river water was observed to follow different kinetics, depending upon the composition and the molecular weight of the copolymer.

Evaluation of the immune response and protective effects of rhesus macaques vaccinated with biodegradable nanoparticles carrying gp120 of human immunodeficiency virus

We previously reported that biodegradable amphiphilic poly(γ-glutamic acid) nanoparticles (NPs) carrying the recombinant gp120 env protein of the human immunodeficiency virus type 1 (HIV-1) were efficiently taken up by dendritic cells, and induced strong CD8+ T cell responses against the gp120 in mice. To evaluate gp120-carrying NPs (gp120-NPs) as a vaccine candidate for HIV-1 infection, we vaccinated rhesus macaques with these gp120-NPs and examined the immune response and protective efficacy against a challenge inoculation of simian and human immunodeficiency chimeric virus (SHIV). We found that gp120-NP vaccination induced stronger responses for both gp120-specific cellular and humoral immunity than gp120-alone vaccination. After the challenge inoculation with SHIV, however, the peak value of viral RNA in the peripheral blood was higher in the vaccinated groups, especially the gp120-NP vaccinated group, than naive control group. Higher value of viral load was also maintained in gp120-NP vaccinated group. Furthermore, CD4+ T cells from the peripheral blood decreased more in the vaccinated groups than the control group. Thus, induced immune responses against gp120 enclosed in NPs were not effective for protection but, conversely enhanced the infection, although the gp120-NPs showed a stronger induction of immune responses against the vaccinated antigen in rhesus macaques. These results support the importance of determining immune correlate of protective immunity for vaccine development against HIV-1 infection.

The nanofibrous architecture of poly( l-lactic acid)-based functional copolymers

It remains a challenge to synthesize functional materials that can develop advanced scaffolding architectures for tissue engineering. In this study, a series of biodegradable amphiphilic poly(hydroxyalkyl (meth)acrylate)-graft-poly( l-lactic acid) (PHAA-g-PLLA) copolymers have been synthesized and fabricated into nano-fibrous scaffolds. These copolymers can be further functionalized, are more hydrophilic, and have faster degradation rates than the PLLA homopolymer, which are advantageous for certain tissue engineering applications. First, PLLA-based macromonomers were prepared by using functional hydroxyalkyl (meth)acrylates (HAA) as initiators. The PHAA-g-PLLA copolymers were then synthesized using free radical copolymerization of PLLA-based macromonomers and HAA. Nano-fibrous architecture was created using a thermally induced phase separation technique from these functional PHAA-g-PLLA copolymers. The nano-fibrous structure mimics the architecture of natural collagen matrix at the nanometer scale. The effects of the macromonomer composition, copolymer composition, blending ratio, and solvent selection on nano-scale structures were studied. In general, the nano-fibrous structure was created when the amount of HAA in the macromonomer was low. By increasing the amount of HAA in the macromonomer, microspheres with nano-fibrous surfaces were obtained. Further increasing the amount of HAA led to the creation of microspheres with leaf-like surfaces. These PLLA-based materials had much faster degradation rates than the PLLA, and could be completely degraded from several weeks to a few months depending on their composition and molecular weight. Furthermore, the PHAA-g-PLLA copolymers possess functional hydroxyl groups, which can be used to couple with bioactive molecules to control cell–material interactions. Therefore, these biodegradable functional copolymers have the design flexibility to fabricate various biomimetic materials for tissue engineering applications.

Biodegradable amphiphilic poly(ethylene oxide)- block-polyesters with grafted polyamines as supramolecular nanocarriers for efficient siRNA delivery

The RNA interference (RNAi) technology has been successfully used in elucidating mechanisms behind various biological events. However, in the absence of safe and effective carriers for in vivo delivery of small interfering RNAs (siRNAs), application of this technology for therapeutic purposes has lagged behind. The objective of this research was to develop promising carriers for siRNA delivery based on degradable poly(ethylene oxide)- block-polyesters containing polycationic side chains on their polyester block. Toward this goal, a novel family of biodegradable poly(ethylene oxide)- block-poly(ɛ-caprolactone) (PEO- b-PCL) based copolymers with polyamine side chains on the PCL block, i.e., PEO- b-PCL with grafted spermine (PEO- b-P(CL- g-SP)), tetraethylenepentamine (PEO- b-P(CL- g-TP)), or N, N-dimethyldipropylenetriamine (PEO- b-P(CL- g-DP)) were synthesized and evaluated for siRNA delivery. The polyamine-grafted PEO- b-PCL polymers, especially PEO- b-P(CL- g-SP), demonstrated comparable toxicity to PEO- b-PCL in vitro. The polymers were able to effectively bind siRNA, self-assemble into micelles, protect siRNA from degradation by nuclease and release complexed siRNA efficiently in the presence of low concentrations of polyanionic heparin. Based on flow cytometry and confocal microscopy, siRNA formulated in PEO- b-P(CL- g-SP) and PEO- b-P(CL- g-TP) micelles showed efficient cellular uptake through endocytosis by MDA435/LCC6 cells transfected with MDR-1, which encodes for the expression of P-glycoprotein (P-gp). The siRNA formulated in PEO- b-P(CL- g-SP) and PEO- b-P(CL- g-TP) micelles demonstrated effective endosomal escape after cellular uptake. Finally, MDR-1-targeted siRNA formulated in PEO- b-P(CL- g-SP) and PEO- b-P(CL- g-TP) micelles exhibited efficient gene silencing for P-gp expression. The results of this study demonstrated the promise of novel amphiphilic PEO- b-P(CL- g-polyamine) block copolymers for efficient siRNA delivery.

Supramolecular hydrogels based on inclusion complexation between poly(ethylene oxide)‐b‐poly (ε‐caprolactone) diblock copolymer and α‐cyclodextrin and their controlled release property

Supramolecular hydrogels formed through inclusion complexation between high molecular weight poly(ethylene oxide) (PEO) and alpha-cyclodextrin (alpha-CD) showed the most sustained release kinetics in vitro with molecular weight of PEO of 35,000 within 5 days. To improve the sustained release and overcome using high molecular weight PEO, novel supramolecular hydrogels have been prepared by using biodegradable amphiphilic poly(ethylene oxide)-b-poly(epsilon-caprolactone) (PEO-PCL) diblock copolymer instead of PEO. Rheologic studies indicate that the prepared hydrogel is thixotropic and reversible. The in vitro release kinetics of hydrogels has been studied by using fluorescein isothiocyanate labeled dextran (dextran-FITC) as model drug. Compared with that of alpha-CD/PEO supramolecular hydrogels, the sustained release of alpha-CD/PEO-PCL supramolecular hydrogel was increased significantly even if with much lower molecular weight of PEO block. This result indicates incorporating hydrophobic PCL block could reduce the molecular weight of PEO required for long-term drug release system. The sustained release is also dependent on the alpha-CD content in supramolecular hydrogels. Thus, the properties of supramolecular hydrogel can be fine-tuned with different polymer and at different alpha-CD content, opening a wide range of applications.

A thermosensitive hydrogel based on biodegradable amphiphilic poly(ethyleneglycol)–polycaprolactone–poly(ethylene glycol) block copolymers**This work was financially supported by the Chinese Key Basic Research Program(2004CB518800 and 2004CB518807), and the Sichuan Key Project of Science andTechnology (06(05SG022-021-02)).

A series of low molecular weight poly(ethylene glycol)–polycaprolactone–poly(ethyleneglycol) (PEG–PCL–PEG) biodegradable block copolymers were successfully synthesizedusing isophorone diisocyanate (IPDI) as the coupling agent, and were characterized using1H NMR and Fourier transform infrared spectroscopy. The aqueous solutions of the PEG–PCL–PEGcopolymers displayed a special thermosensitive gel–sol transition when the concentration wasabove the corresponding critical gel concentration. Gel–sol phase diagrams were recordedusing the test-tube-inversion method; they depended on the hydrophilic/hydrophobicbalance in the macromolecular structure, as well as some other factors, including theheating history, volume, and the ageing time of the copolymer aqueous solutions anddissolution temperature of the copolymers. As a result, the gel–sol transition temperaturerange could be altered, which might be very useful for application in injectable drugdelivery systems.

Amphiphilic Poly(l-lactide)-b-dendritic Poly(l-lysine)s Synthesized with A Metal-Free Catalyst and New Dendron Initiators: Chemical Preparation and Characterization

This study presents investigations on new approaches to novel biodegradable amphiphilic poly(L-lactide)-b-dendritic poly(L-lysine)s bearing well-defined structures. First, two new Boc-protected poly(L-lysine) dendron initiators G(2)OH 4 (generation = 2) and G(3)OH 6 (generation = 3) with hydroxyl end functional groups were efficiently derived from corresponding precursors 3 and 5 via methyl ester substitution with ethanolamine. Subsequently, two series of new diblock copolymers of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s (S1-S2, S3-S4) were prepared in chloroform through ring-opening copolymerization of poly(L-lactide)s with a metal-free catalyst of organic 4-(dimethylamino) pyridine (DMAP) in the presence of a corresponding new poly(L-lysine) dendron initiator. Further, molecular structures of the prepared new dendron initiators as well as those of poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s bearing different dendron blocks and PLLA lengths were examined by means of nuclear magnetic resonance spectroscopy (NMR), gel permeation chromatography (GPC), mass spectrometry (ESI-MS, MALDI-FTMS), and thermal gravimetric analysis (TGA). The results demonstrated successful formation of the synthetic precursors, functional dendron initiators, and new diblock copolymers. In addition, the very narrow molecular weight distributions (PDI = 1.10-1.14) of these poly(L-lactide)-b-dendritic Boc-protected poly(L-lysine)s further indicated their well-defined molecular structures. After the efficient Boc-deprotection for the dendron amino groups with TFA/CH(2)Cl(2), new diblock poly(L-lactide)-b-dendritic poly(L-lysine)s bearing lipophilic PLLA and hydrophilic dendritic PLL were finally prepared. It was noteworthy that the MALDI-FTMS result showed that no appreciable intermolecular chain transesterification happened during the ROP of L-lactide catalyzed by the DMAP. Moreover, self-assembly of these new biodegradable amphiphilic copolymers in diverse solvents were also preliminarily studied.

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.

Micellization Phenomena of Biodegradable Amphiphilic Triblock Copolymers Consisting of Poly(β-hydroxyalkanoic acid) and Poly(ethylene oxide)

This paper reports the studies on micelle formation of new biodegradable amphiphilic poly(ethylene oxide)-poly[(R)-3-hydroxybutyrate]-poly(ethylene oxide) (PEO-PHB-PEO) triblock copolymer with various PHB and PEO block lengths in aqueous solution. Transmission electron microscopy showed that the micelles took an approximately spherical shape with the surrounding diffuse outer shell formed by hydrophilic PEO blocks. The size distribution of the micelles formed by one triblock copolymer was demonstrated by dynamic light scattering technique. The critical micellization phenomena of the copolymers were extensively studied using the pyrene fluorescence dye absorption technique, and the (0,0) band changes of pyrene excitation spectra were used as a probe for the studies. For the copolymers studied in this report, the critical micelle concentrations ranged from 1.3 x 10(-5) to 1.1 x 10(-3) g/mL. For the same PEO block length of 5000, the critical micelle concentrations decreased with an increase in PHB block length, and the change was more significant in the short PHB range. It was found that the micelle formation of the biodegradable amphiphilic triblock copolymers consisting of poly(beta-hydroxyalkanoic acid) and PEO was relatively temperature-insensitive, which is quite different from their counterparts consisting of poly(alpha-hydroxyalkanoic acid) and PEO.

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.