Expanding Cyclic Topology-Based Biomedical Polymer Panel: Universal Synthesis of Hetero-"8"-Shaped Copolymers and Topological Modulation of Polymer Degradation.

8-Shaped copolymers with two macrocycles connected together represent an interesting cyclic topology-derived polymer species due to the simultaneous incorporation of two cyclic moieties and the reported unique physical and chemical properties. To provide a proof-of-concept for a broad readership on biomedical polymers, a well-defined hetero-8-shaped amphiphilic copolymer, cyclic-poly(oligo(ethylene glycol)monomethyl ether methacrylate)-b-cyclic PCL (cPOEGMA-b-cPCL) is synthesized by an elegant integration of intrachain click cyclization and interchain click coupling. The potential of the self-assembled micelles of cPOEGMA-b-cPCL for controlled drug release is evaluated by in vitro drug loading and drug release, cellular uptake, cytotoxicity, and degradation studies. Most importantly, the micelles based on cPOEGMA-b-cPCL show much slower degradation profiles than the previously reported linear counterpart, POEGMA-b-PCL and tadpole-shaped analog, PEG-b-cPCL because of the presence of cyclic hydrophilic POEGMA segment. Therefore, this study not only develops a robust strategy for a universal precise synthesis of well-defined hetero-8-shaped copolymers based on diverse vinyl and ring-structured monomers, but also reveals the first modulation of polymer degradation property by topological control of the nondegradable moiety in the polymer construct through advanced macromolecular engineering.

Fabrication of Thermosensitive Cyclic Brush Copolymer with Enhanced Therapeutic Efficacy for Anticancer Drug Delivery.

Adaptation of cyclic brush polymer for drug delivery applications remains largely unexplored. Herein, cyclic brush copolymer of poly(2-hydroxyethyl methacrylate-g-poly(N-isopropylacrylamide-st-N-hydroxyethylacrylamide)) (cb-P(HEMA-g-P(NIPAAm-st-HEAAm))), comprising a cyclic core of PHEMA and thermosensitive brushes of statistical copolymer of P(NIPAAm-st-HEAAm), is designed and synthesized successfully via a graft-from approach using atom transfer free radical polymerization from a cyclic multimacroinitiator. The composition of the brush is optimized to endow the resulting cyclic brush copolymer with a lower critical solution temperature (LCST) slightly above the physiological temperature, but lower than the localized temperature of tumor tissue, which is suitable for the hyperthermia-triggered anticancer drug delivery. Critical aggregation concentration determination reveals better stability for the unimolecular nanoparticle formed by the cyclic brush copolymer than that formed by the bottlebrush analogue. The dramatically increased size with elevated temperatures from below to above the LCST confirms hyperthermia-induced aggregation for both formulations. Such structural destabilization promotes significantly the drug release at 40 °C. Most importantly, the drug-loaded cyclic brush copolymer shows enhanced in vitro cytotoxicity against HeLa cells than the bottlebrush counterpart. The better stability and higher therapeutic efficacy demonstrates that the thermosensitive cyclic brush copolymer is a better formulation than bottle brush copolymer for controlled drug release applications.

A nanobody-mediated drug system against largemouth bass virus delivered by bacterial nanocellulose in Micropterus salmoides.

Diseases caused by pathogens severely hampered the development of aquaculture, especially largemouth bass virus (LMBV) has caused massive mortality and severe economic losses to the culture of largemouth bass (Micropterus salmoides). Considering the environmental hazards and human health, effective and environmentally friendly therapy strategy against LMBV is of vital importance and in pressing need. In the present study, a novel nanobody (NbE4) specific for LMBV was selected from a phage display nanobody library. Immunofluorescence and indirect ELISA showed that NbE4 could recognize LMBV virions and had strong binding capacity, but RT-qPCR evidenced that NBE4 did not render the virus uninfectious. Besides, antiviral drug ribavirin was used to construct a targeted drug system delivered by bacterial nanocellulose (BNC). RT-qPCR revealed that NbE4 could significantly enhance the antiviral activity of ribavirin in vitro and in vivo. The targeted drug delivery system (BNC-Ribavirin-NbE4, BRN) reduced the inflammatory response caused by LMBV infection and improved survival rate (BRN-L, 33.3 %; BRN-M, 46.7 %; BRN-H, 56.7 %)compared with control group (13.3 %), ribavirin group (RBV, 26.7 %) and BNC-ribavirin (BNC-R, 40.0 %), respectively. This research provided an effective antiviral strategy that improved the drug therapeutic effect and thus reduced the dosage.

Toward function starch nanogels by self-assembly of polysaccharide and protein: From synthesis to potential for polyphenol delivery.

Nanogels formed by self-assembly of natural proteins and polysaccharides have attracted great interest as potential carriers of bioactive molecules. Herein, we reported that carboxymethyl starch-lysozyme nanogels (CMS-Ly NGs) were prepared using carboxymethyl starch and lysozyme by green and facile electrostatic self-assembly, and the nanogels served as epigallocatechin gallate (EGCG) delivery systems. The dimensions and structure of the prepared starch-based nanogels (i.e., CMS-Ly NGs) were characterized by dynamic light scattering (DLS), ζ-potential, Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and thermal gravimetric analyzer (TGA). FT-IR and 1H NMR spectra together confirmed the formation of CMS; FT-IR spectra confirmed the formation of CMS-Ly NGs; XRD spectra confirmed the disruption of the crystal structure of lysozyme after electrostatic self-assembly with CMS, and further confirmed the formation of nanogels. TGA demonstrated the thermal stability of nanogels. More importantly, the nanogels showed a high EGCG encapsulation rate of 80.0 ± 1.4 %. The CMS-Ly NGs encapsulated with EGCG exhibited regular spherical structure and stable particle size. Under the simulated gastrointestinal environmental conditions, CMS-Ly NGs encapsulated with EGCG showed the controlled release potential, which increased its utilization. Additionally, anthocyanins can also be encapsulated in CMS-Ly NGs and showed slow-release properties during gastrointestinal digestion in the same way. Cytotoxicity assay also demonstrated good biocompatibility between CMS-Ly NGs and CMS-Ly NGs encapsulated with EGCG. The findings of this research suggested the potential application of protein and polysaccharides-based nanogels in the delivery system of bioactive compounds.

Nanomaterials for Targeted Delivery of Agrochemicals by an All-in-One Combination Strategy and Deep Learning.

The development of modern agriculture has prompted the greater input of herbicides, insecticides, and fertilizers. However, precision release and targeted delivery of these agrochemicals still remain a challenge. Here, a pesticide-fertilizer all-in-one combination (PFAC) strategy and deep learning are employed to form a system for controlled and targeted delivery of agrochemicals. This system mainly consists of three components: (1) hollow mesoporous silica (HMS), to encapsulate herbicides and phase-change material; (2) polydopamine (PDA) coating, to provide a photothermal effect; and (3) a zeolitic imidazolate framework (ZIF8), to provide micronutrient Zn2+ and encapsulate insecticides. Results show that the PFAC at concentration of 5 mg mL-1 reaches the phase transition temperature of 1-tetradecanol (37.5 °C) after 5 min of near-infrared (NIR) irradiation (800 nm, 0.5 W cm-2). The data of corn and weed are collected and relayed to deep learning algorithms for model building to realize object detection and further targeted weeding. In-field treatment results indicated that the growth of chicory herb was significantly inhibited when treated with the PFAC compared with the blank group after 24 h under NIR irradiation for 2 h. This system combines agrochemical innovation and artificial intelligence technology, achieves synergistic effects of weeding and insecticide and nutrient supply, and will potentially achieve precision and sustainable agriculture.

A near-infrared laser and H2O2 activated bio-nanoreactor for enhanced photodynamic therapy of hypoxic tumors.

Hypoxic resistance, photosensitizer toxicity, and target deficiency are major challenges strongly inhibiting the efficacy of clinical photodynamic therapy (PDT) in tumor treatment. To overcome these challenges, we synthesized IR780 and catalase co-loaded liposomes to form a tumor-targeted bio-nanoreactor (LIP-IR-CAT). The efficient strategy can solve the physicochemical problems including strong hydrophobicity, poor light stability, poor tolerance, and high toxicity in vivo of IR780 as a photosensitizer and promote the clinical application of IR780. Taking advantage of the high catalytic efficiency of catalase when it meets hydrogen peroxide (H2O2), continuous oxygen can be generated due to the abnormally elevated level of H2O2 within the tumor, thus remarkably promoting tumor oxygenation. With the conjunction of photosensitivity and specific mitochondria-targeting ability of IR780, the intratumoral reactive oxygen species (ROS) are strongly enhanced, and adenosine triphosphate (ATP) is reduced under near-infrared (NIR) laser irradiation. Following a single-dose intravenous injection of LIP-IR-CAT, tumor hypoxia can be seriously attenuated, at the same time creating an opportunity to enhance the efficacy of PDT on the tumor. Our in vivo data show that the nanoreactor LIP-IR-CAT, in combination with just two short time NIR laser irradiation sessions, can effectively inhibit the growth of solid tumors without systemic toxicity.

Diagnosis of Mild Cognitive Impairment and Alzheimer's Disease by the Plasma and Serum Amyloid-beta 42 Assay through Highly Sensitive Peptoid Nanosheet Sensor.

Alzheimer's disease (AD) is the most common neurodegenerative disorder with a continuous pathophysiological process starting from the preclinical and mild cognitive impairment (MCI) phases to the dementia phase. Early diagnosis is prerequisite for the early intervention of AD but meanwhile challenging. Amyloid-beta 1-42 (Aß42) plays a crucial part in AD pathology. Positron-emission tomography (PET) imaging of Aß42 in the brain and the measurement of Aß42 in the cerebrospinal fluid (CSF) have been adopted for the auxiliary diagnosis of AD, but their widespread clinical application has been limited due to the radiation and the high-cost of PET and the invasive lumbar puncture for collecting CSF. Noninvasive and cost-effective blood-based assay is desirable for the early diagnosis of AD. Here, a label-free assay for the quantification of blood Aß42 was developed using the high-throughput surface plasmon resonance imaging method with the aid of an antibody-mimetic peptoid nanosheet equipping Aß42-recognizing loops. We demonstrated that this nanosheet-based sensor system could distinguish the plasma and sera from normal individuals and patients suffering AD and amnestic MCI with high sensitivity and specificity, preceding the diagnostic performance of the Aß42-recognizing molecule and the antibody specific to Aß42. This work provides a label-free, cost-effective, highly sensitive, and high-throughput blood-based assay for early detection of AD.

A nano polymer conjugate for dual drugs sequential release and combined treatment of colon cancer and thrombotic complications.

Thrombotic complications turn into the second leading cause of death in colon cancer patients due to the hypercoagulable state caused by malignancy. Therefore, it is necessary to treat colon cancer and its thrombosis complications simultaneously. Herein, a nano polymer conjugate based on disulfide cross-linked low-generation peptide dendrimers was developed to treat colon cancer and its thrombotic complications. First, two-generation polyglutamic acid dendrimer was bonded to nattokinase (NK) and then cross-linkers containing disulfide linkages were used to obtain polymer conjugates (NK-G2)n. Then doxorubicin (Dox) was encapsulated. The system can release drugs sequentially due to the dissociation of the polymer conjugates. In vitro thrombolytic experiments exhibited a significant thrombolysis ability of (NK-G2)n. The toxicity and cellular uptake tests on HCT116 cells showed that Dox loaded polymer conjugates had good endocytosis ability and anti-cancer effect. Therefore, this drug delivery system will be a promising strategy to the combined treatment of colon cancer and thrombotic complications.

IR780-based light-responsive nanocomplexes combining phase transition for enhancing multimodal imaging-guided photothermal therapy.

Near-infrared (NIR) light-triggered photothermal therapy (PTT) has been widely applied for treating cancer. The combination of nanotechnology and NIR has shown great promise for promoting the efficacy of PTT. However, PTT alone could not completely ablate the tumors and easily causes tumor recurrence. To overcome this challenge, many studies have been performed to enhance PTT, including combining chemical therapy and radiotherapy, both of which have side effects on the body. To reduce the side effects and enhance PTT, a new infrared IR780-based nanocomplex combining liquid fluorocarbon perfluoropentane (PFP) has been synthesized for enhancing multimodal imaging-guided PTT. Under NIR irradiation, the size changes of PFP-loaded nanobubbles transforming into microbubbles allow ultrasound (US) imaging, showing boundaries and internal information of tumors. The breakup process and cascade reaction of phase transition can improve intratumoral permeation and retention of nanoparticles in nonmicrovascular tissue and damage the cell membranes of tumors, further enhancing PTT to kill tumor cells. The strong absorption in the NIR field of IR780-loaded NPs allows not only photoacoustic (PA) imaging but also NIR fluorescence (NIRF) imaging, which provides more anatomical information about tumors. This nanocomplex exhibits good biocompatibility and nontoxicity, strong PA/US/NIRF imaging contrast, excellent liquid-gas transition and a photothermal effect. This finding provides a new method to enhance multimodal imaging-guided cancer nanotheranostics.

A multielement compound fertilizer used polydopamine and sodium carboxymethyl starch matrices as coatings.

In this work, a multielement compound fertilizer (MCF) was fabricated using ammonium zinc phosphate (AZP) as kernel nutrient element, and polydopamine (Pdop) film as inner coating. Besides, sodium carboxymethyl starch (SCS) was proposed as a constituent in AZP@Pdop mixture due to its adhesion, gelling and swelling abilities, to prepare well dispersed suspensions and consolidate the single-coated fertilizer. What's more, iron (Fe), the vital microelement for the growth of crops and alleviating the leaf chlorosis, was chelated by the carboxylate groups of SCS, contributing to make the outer coating compact. The release behavior showed that zinc (Zn), phosphorus (P) and Fe reached 60% cumulative release in 30 days, and the use efficiency of nutrients for corn was about 60%. In summary, this work provides a novel approach to improve the utilization efficiency and prolong duration of the MCF, which might have a potential application in agronomics.

Preparation of ionic-crosslinked chitosan-based gel beads and effect of reaction conditions on drug release behaviors.

Drug-loaded chitosan (CS) beads were prepared under simple and mild condition using trisodium citrate as ionic crosslinker. The beads were further coated with poly(methacrylic acid) (PMAA) by dipping the beads in PMAA aqueous solution. The surface and cross-section morphology of these beads were observed by scanning electron microscopy and the observation showed that the coating beads had core-shell structure. In vitro release of model drug from these beads obtained under different reaction conditions was investigated in buffer medium (pH 1.8). The results showed that the rapid drug release was restrained by PMAA coating and the optimum conditions for preparing CS-based drug-loaded beads were decided through the effect of reaction conditions on the drug release behaviors. In addition, the drug release mechanism of CS-based drug-loaded beads was analyzed by Peppa's potential equation. According to this study, the ionic-crosslinked CS beads coated by PMAA could serve as suitable candidate for drug site-specific carrier in stomach.

Synthesis and characterization of a nano fluorescent starch.

A novel nano fluorescent starch, starch-bearing 3-epoxypropoxy fluorescein (ST-EF) was developed by a simple method. First, 3-epoxypropoxy fluorescein (EF) was prepared via a nucleophilic substitution reaction between fluorescein and epichlorohydrin. Then, ST-EF was synthesized via a ring-opening reaction to attach fluorescein to native cassava starch chains. The degree of substitution (DS) of ST-EF was determined by ultraviolet-visible spectrophotometry. The 1H nuclear magnetic resonance (NMR) spectroscopy, elemental analysis, fourier transformed infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), transmission electron microscope (TEM), dynamic laser scattering (DLS), X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were used to characterize ST-EF. Fluorescent properties of ST-EF in water were studied. The results showed that the nano fluorescent starch shows strong fluorescence as fluorescein, and can be used as a fluorescent polymer in various applications, especially in biomedicine.

Multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer: Design, synthesis, and dissolving thrombus.

Thrombotic events affect many individuals in a number of ways, all of which can cause significant morbidity and mortality. Nattokinase (NK), as a novel thrombolytic drug, has been used for thrombolytic therapy. It not only possesses plasminogen activator activity, but also directly digests fibrin through limited proteolysis. However, it may undergo inactivation and denaturation in the harsh external environment. In this study, a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer was fabricated and used as a carrier for NK protection and delivery. Different arm numbers of polyethylene glycol-polyglutamic acid peptide dendrimers (x-PEG(G3 )x , x = 2, 4, 6, 8) were designed, prepared, and characterized by 1 H NMR and FTIR. Then, x-PEG(G3 )x were loaded with NK to form nanocomposites. Their size and morphology were determined by dynamic light scattering and transmission electron microscopy. Enzyme activity was evaluated via UV-Vis absorbance spectra, fluorescence spectra, circular dichroism spectra, and zeta potential measurements. The study reveals that the obtained x-PEG(G3 )x /NK nanocomposites possess high enzyme activity. In addition, the nanocomposites show increased viability of rat macrophage cells, and excellent thrombolysis ability in vitro and in vivo. This work establishes a multiarm-polyethylene glycol-polyglutamic acid peptide dendrimer with potential application in NK carrier and thrombolytic therapy. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1687-1696, 2018.

High encapsulation and localized delivery of curcumin from an injectable hydrogel.

Most chemotherapy currently available for cancer treatment has limited potential to successful clinical cancer therapy, mainly due to low encapsulating capacity of drugs and unavailable pharmacologically beneficial concentrations at the tumor site. Herein, a novel yet simple strategy is developed to enhance drug encapsulating capacity and localized drug concentration using an injectable hydrogel based on thiolated chitosan (TCS) and poly(ethylene glycol) diacrylate (PEGDA). Almost 100% of encapsulating capacity is achieved when anti-cancer drug curcumin is encapsulated in the system. The interaction of curcumin with PEGDA is determined by fluorescence spectroscopy and the binding constant is calculated, followed by a simulation by a docking study using AutoDock. To improve the anti-tumor activity and achieve effective local concentrations, lysozyme is introduced into the system. Sustained curcumin release in a controlled lysozyme-responsive behaviour is observed, which enables the drug concentration to reach the therapeutic threshold promptly. The system displays efficient intracellular curcumin release to promote cancer cells apoptosis in vitro. In addition, the system effectively delays the tumor growth and reduces adverse effects in tumor-bearing nude mice. The strategy of localized, high encapsulation of drug by using an injectable hydrogel would be particularly beneficial with many insoluble anti-cancer drugs.

Fabrication of Reduction-Sensitive Amphiphilic Cyclic Brush Copolymer for Controlled Drug Release.

The cyclic brush polymers, due to the unique topological structure, have shown in the previous studies higher delivery efficacy than the bottlebrush analogues as carriers for drug and gene transfer. However, to the best of knowledge, the preparation of reduction-sensitive cyclic brush polymers for drug delivery applications remains unexplored. For this purpose, a reduction-sensitive amphiphilic cyclic brush copolymer, poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)-disulfide link-poly(oligoethyleneglycol methacrylate)) (P(HEMA-g-PCL-SS-POEGMA)) with reducible block junctions bridging the hydrophobic PCL middle layer and the hydrophilic POEGMA outer corona is designed and synthesized successfully in this study via a "grafting from" approach using sequential ring-opening polymerization (ROP) and atom transfer free radical polymerization (ATRP) from a cyclic multimacroinitiator PHEMA. The resulting self-assembled unimolecular core-shell-corona (CSC) micelles show sufficient salt stability and efficient destabilization in the intracellular reducing environment for a promoted drug release toward a greater therapeutic efficacy relative to the reduction-insensitive analogues. The overall results demonstrate the reducible cyclic brush copolymers developed herein provides an elegant solution to the tradeoff between extracellular stability and intracellular high therapeutic efficacy toward efficient anticancer drug delivery.

Preparation, characterization and controlled release investigation of interpenetrating polymer networks of poly(acrylic acid)/triazole modified poly(vinyl alcohol).

A series of interpenetrating polymer networks of poly(acrylic acid) (PAA)/triazole modified poly(vinyl alcohol) (TMIPNs) were synthesized by radical polymerization in methanol at room temperature with l-ascorbic acid (Vc) and peroxide hydrogen (H2O2) as initiators and trihydroxymethyl propane glycidol ether (6360) as a crosslinker. The structures of the gels were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The swelling/deswelling behavior of hydrogels was studied in different pH and different concentrations of NaCl aqueous solutions. The results showed that the TMIPNs hydrogels had excellent pH- and salt-sensitivity in the range of the investigation. The mechanism of the swelling and the deswelling was discussed and the results were confirmed further by scanning electron microscope (SEM). In addition, the controlled release behavior of TMIPNs in vitro was also studied. The effects of physical stimulus (ultraviolet ray and ultrasonic wave), salt concentration, pH value and the swelling/deswelling on the controlled released behavior were also explored.

Dual crosslinked chondroitin sulfate injectable hydrogel formed via continuous Diels-Alder (DA) click chemistry for bone repair.

In the present work, a thermosensetive copolymer with a low gelation concentration under 37°C, F127@ChS (F127 crosslinked chondroitin sulfate) was synthesized via DA click chemistry between F127-AMI (maleimido terminated F127) and ChS-furan (furfurylamine grafted chondroitin sulfate). Then, dual crosslinked hydrogels were prepared based on F127@ChS and PEG-AMI (maleimido terminated polyethylene glycol). The physical crosslinking of F127@ChS affords the hydrogel fast gelation behavior, while in situ DA click reaction occurred between F127@ChS and PEG-AMI affords the hydrogel system covalent crosslinking. The dual crosslinked injectable hydrogel was applied as scaffold to load BMP-4 for rat cranial defect repair. As indicated by X-ray imaging, cranial digital images and histological (HE and Masson) staining analysis, new bone tissues were formed in the defected area after 12 weeks repair. The results demonstrate that the novel dual crosslinked injectable hydrogel offer an interesting option for cranial bone tissue engineering.

CO2-switchable fluorescence of a dendritic polymer and its applications.

The synthesis and properties of CO2 responsive and fluorescent dendritic polymers, poly(amido amine)/Pluronic F127 (PAMAM/F127), are reported in this paper. The morphologies and sizes of PAMAM/F127 dendritic polymers were investigated by dynamic light scattering (DLS) and transmission electron microscopy (TEM). PAMAM/F127 dendritic polymers showed unimolecular micelle morphologies at low concentrations, and changed to multimolecular micelles at higher concentrations. Additionally, fluorescence spectra and confocal laser scanning microscopy images showed that PAMAM/F127 dendritic polymers exhibited a fluorescent enhancement response to the presence of CO2. Apart from that, the release behavior of PAMAM/F127 gels under simulated body fluids was investigated by choosing curcumin as the hydrophobic drug. The results indicated that PAMAM/F127 dendritic polymers can be used to improve the solubility of curcumin, and the drug released faster in the presence of CO2. Such CO2 responsive fluorescent dendritic polymers are potentially applicable in cellular imaging or drug controlled release.

Mucoadhesive microparticulates based on polysaccharide for target dual drug delivery of 5-aminosalicylic acid and curcumin to inflamed colon.

In this work, thiolated chitosan/alginate composite microparticulates (CMPs) coated by Eudragit S-100 were developed for colon-specific delivery of 5-aminosalicylic acid (5-ASA) and curcumin (CUR), and the use of it as a multi drug delivery system for the treatment of colitis. The physicochemical properties of the CMPs were evaluated. In vitro release was performed in gradually pH-changing medium simulating the conditions of different parts of GIT, and the results showed that the Eudragit S-100 coating has a pH-sensitive release property, which can avoid drug being released at a pH lower than 7. An everted sac method was used to evaluate the mucoadhesion of CMPs. Ex vivo mucoadhesive tests showed CMPs have excellent mucosa adhesion for the colonic mucosa of rats. In vivo treatment effect of enteric microparticulates systems was evaluated in colitis rats. The results showed superior therapeutic efficiency of this drug delivery system for the colitis rats induced by TNBS. Therefore, the enteric microparticulates systems combined the properties of pH dependent delivery, mucoadhesive, and control release, and could be an available tool for the treatment of human inflammatory bowel disease.

Fluorescence probe studies on the complexation between poly(methacrylic acid) and poly(N, N-diethylacrylamide).

The complexation between poly(methacrylic acid) (PMAA) and poly(N, N-diethylacrylamide) (PDEAM) in aqueous phase was studied by UV-vis and fluorescence probe techniques. It was demonstrated that the complexation of PMAA with PDEAM occurs within a pH range of 1-6.5 and along with the complexation, the conformation of PMAA changed from a hypercoiled to a loose coiled form. The complex ratio between the two polymers is 1:1 (PMAA:PDEAM, in monomer unit). Salt effect studies showed that the complexation occurred due to formation of hydrogen bonds between the two polymers. Based upon these conclusions and the "compact micelle-like structure" for PMAA at low pH, a "ladder" model was proposed for the structure of PMAA-PDEAM complex formed at low pH.