The role of critical micellization concentration in efficacy and toxicity of supramolecular polymers.

The inception and development of supramolecular chemistry have provided a vast library of supramolecular structures and materials for improved practice of medicine. In the context of therapeutic delivery, while supramolecular nanostructures offer a wide variety of morphologies as drug carriers for optimized targeting and controlled release, concerns are often raised as to how their morphological stability and structural integrity impact their in vivo performance. After intravenous (i.v.) administration, the intrinsic reversible and dynamic feature of supramolecular assemblies may lead them to dissociate upon plasma dilution to a concentration below their critical micellization concentration (CMC). As such, CMC represents an important characteristic for supramolecular biomaterials design, but its pharmaceutical role remains elusive. Here, we report the design of a series of self-assembling prodrugs (SAPDs) that spontaneously associate in aqueous solution into supramolecular polymers (SPs) with varying CMCs. Two hydrophobic camptothecin (CPT) molecules were conjugated onto oligoethylene-glycol (OEG)-decorated segments with various OEG repeat numbers (2, 4, 6, 8). Our studies show that the lower the CMC, the lower the maximum tolerated dose (MTD) in rodents. When administrated at the same dosage of 10 mg/kg (CPT equivalent), SAPD 1, the one with the lowest CMC, shows the best efficacy in tumor suppression. These observations can be explained by the circulation and dissociation of SAPD SPs and the difference in molecular and supramolecular distribution between excretion and organ uptake. We believe these findings offer important insight into the role of supramolecular stability in determining their therapeutic index and in vivo efficacy.

Gradient structure-induced temperature responsiveness in styrene/methyl methacrylate gradient copolymers micelles.

In this work, micelles are formed by gradient copolymer of styrene and methyl methacrylate in acetone-water mixture and their temperature responsiveness is investigated in a narrow range near room temperature. Three different kinds of structural transitions could be induced by temperature: unimers to micelle transition, shrinkage/stretching of micelles, and morphological transition from spherical micelles to vesicles. In addition, a model analysis on the interface of gradient copolymer micelle is made to better understand these phenomena. It is found that both position and composition of the interface could alter in response to the change in temperature. According to the experiments and model analysis, it is proposed that temperature responsiveness might be an intrinsic and universal property of gradient copolymer micelles, which only originates from the gradient structure.

Chemical conjugation mitigates immunotoxicity of chemotherapy via reducing receptor-mediated drug leakage from lipid nanoparticles.

Immunotoxicity remains a major hindrance to chemotherapy in cancer therapy. Nanocarriers may alleviate the immunotoxicity, but the optimal design remains unclear. Here, we created two variants of maytansine (DM1)-loaded synthetic high-density lipoproteins (D-sHDL) with either physically entrapped (ED-sHDL) or chemically conjugated (CD-sHDL) DM1. We found that CD-sHDL showed less accumulation in the tumor draining lymph nodes (DLNs) and femur, resulting in a lower toxicity against myeloid cells than ED-sHDL via avoiding scavenger receptor class B type 1 (SR-B1)-mediated DM1 transportation into the granulocyte-monocyte progenitors and dendritic cells. Therefore, higher densities of lymphocytes in the tumors, DLNs, and blood were recorded in mice receiving CD-sHDL, leading to a better efficacy and immune memory of CD-sHDL against colon cancer. Furthermore, liposomes with conjugated DM1 (CD-Lipo) showed lower immunotoxicity than those with entrapped drug (ED-Lipo) through the same mechanism after apolipoprotein opsonization. Our findings highlight the critical role of drug loading patterns in dictating the biological fate and activity of nanomedicine.

Synthesis and theoretical study of molecularly imprinted monoliths for HPLC.

Molecularly imprinted monoliths integrate the high permeability of monolithic materials and the high selectivity and affinity of molecularly imprinted polymers (MIP). Thus, in recent years, development of this novel MIP format in HPLC has expanded quickly, particularly use of organic materials. This review focuses on the principal aspects of good practice in polymerization, theoretical studies, and recent developments in molecularly imprinted monoliths. Some thoughts on perspectives of MIP monoliths are also expressed.

Micellization of St/MMA gradient copolymers: a general picture of structural transitions in gradient copolymer micelles.

In this work, a gradient copolymer of styrene (St) and methyl methacrylate (MMA) is synthesized via reversible addition-fragmentation chain transfer living radical polymerization and its micellization behaviors in an acetone and water mixture are investigated by transmission electron microscopy, light scattering, and NMR spectroscopy. Three different kinds of transitions were found to coexist in a single system for the first time: a unimers to micelles transition, a star-like micelles to crew-cut micelles transition resulting from the shrinkage of micelles, and morphological transitions from spherical micelles to cylindrical micelles to vesicles. Our findings provide a general picture of structural transitions and relaxation processes in gradient copolymer micelles, which can lead to the development of novel materials and applications based on gradient copolymers.

Recent developments and applications of molecularly imprinted monolithic column for HPLC and CEC.

As a new generation of stationary phases, monolithic supports have attracted significant interest in high-performance liquid chromatography (HPLC) and capillary electrochromatography (CEC) because of their ease of preparation, high reproducibility, versatile surface chemistry and rapid mass transport. Molecularly imprinted polymers (MIPs) are synthetic materials with high specific recognition ability to template molecule. The combination of monolithic column and MIPs integrates the high efficiency of modern chromatography and the high selectivity provided by MIPs. This review focuses on the recent developments and applications of all kinds of monolithic matrix, i.e. organic polymer-based and silica-based MIP monolith in HPLC and CEC mode.

Recent Progress in the Design and Application of Supramolecular Peptide Hydrogels in Cancer Therapy.

Supramolecular peptide hydrogel (SPH) is a class of biomaterials self-assembled from peptide-based gelators through non-covalent interactions. Among many of its biomedical applications, the potential of SPH in cancer therapy has been vastly explored in the past decade, taking advantage of its good biocompatibility, multifunctionality, and injectability. SPHs can exert localized cancer therapy and induce systemic anticancer immunity to prevent tumor recurrence, depending on the design of SPH. This review first gives a brief introduction to SPH and then outlines the major types of peptide-based gelators that have been developed so far. The methodologies to tune the physicochemical properties and biological activities are summarized. The recent advances of SPH in cancer therapy as carriers, prodrugs, or drugs are highlighted. Finally, the clinical translation potential and main challenges in this field are also discussed.

Multifunctional gap-enhanced Raman tags for preoperative and intraoperative cancer imaging.

Multi-modality imaging agents are desirable for tumor diagnosis because they can provide more alternative and reliable information for accurate detection and therapy of diseases than single imaging technique. However, most reported conventional imaging agents have not been found to successfully overcome the disadvantages of traditional diagnoses such as sensitivity, spatial resolution, short half-decay time and complexity. Therefore, exploring a multifunctional nanocomposite with the combination of their individual modality characteristics has great impact on preoperative imaging and intraoperative diagnosis of cancer. In our study, mesoporous silica gadolinium-loaded gap-enhanced Raman tags (Gd-GERTs) specifically for preoperative and intraoperative imaging are designed and their imaging capability and biosafety are examined. They exhibit strong attenuation property for computed X-ray tomography (CT) imaging, high T1 relaxivity for magnetic resonance (MR) imaging capability and surface-enhanced Raman spectroscopy (SERS) signal with good dispersity and stability, which presents CT/MR/SERS multi-mode imaging performance of the tumor of mice within a given time. Furthermore, in vivo biodistribution and long-term toxicity studies reveal that the Gd-GERTs have good biocompatibility and bio-safety. Therefore, Gd-GERTs are of great potential as a multifunctional nanoplatform for accurate preoperative CT/MRI diagnosis and intraoperative Raman imaging-guide resection of cancers. STATEMENT OF SIGNIFICANCE: Recent advances in molecular imaging technology have provided a myriad of opportunities to prepare various nanomaterials for accurate diagnosis and response evaluation of cancer via different imaging modalities. However, single bioimaging modality is still challenging to overcome the issues such as sensitivity, spatial resolution, imaging speed and complexity for clinicians. In this work, we designed a kind of unique multifunctional nanoprobes with computed X-ray tomography/magnetic resonance/surface-enhanced Raman spectroscopy (CT/MR/SERS) triple-modal imaging capabilities. Multifunctional nanotags offer the capabilities of preoperative noninvasive CT/MR imaging for identification of tumors as well as intraoperative real-time SERS imaging for guidance of complete resection of tumors. These multifunctional nanoprobes show critical clinical significance on the improvement of tumor diagnosis and therapy.

Preparation of magnetic mesoporous epoxy resin by initiator-free ring-opening polymerization for extraction of bile acids from human serum.

In this work, we reported a simple two-step method for the synthesis of magnetic mesoporous epoxy resin (MMER), including one-pot template-free hydrothermal synthesis of nanoscale amine-functionalized magnetic nanoparticles (MN-NH2) and initiator-free ring-opening polymerization of epoxy resin. The resultant MMER was characterized in detail by transmission electron microscope (TEM), Fourier transform-infrared (FT-IR) spectra, X-ray photoelectron spectroscopy (XPS), thermogravimetic analysis (TGA) and magnetization curves. These results demonstrated successful synthesis of MMER with sufficient magnetic property and excellent thermal stability. The epoxy resin was covalent bonding MN-NH2 on and synthesized by hydrophobic monomers, so the MMER exhibited excellent adsorption quantity for hydrophobic bile acids. The MMER was used as magnetic solid-phase extraction (MSPE) sorbent, and combined with liquid chromatography-tandem mass spectrometry to extract and monitor 11 kinds of bile acids from serum sample. The proposed MSPE combined with LC-MS/MS method exhibited low limit of detection between 0.1 and 5 ng mL-1. In blank serum sample, 9 kinds of bile acids were detected, and ranged from -2.29 ng mL-1 to 6.86 ng mL-1. In standard addition recovery test, the recovery values of detectable bile acids ranged 102.4% to 108.5%, 96.0% to 104.0% and 82.3% to 103.3% when spiked with 0.2, 2.0 and 20 ng mL-1, respectively. The intra- and inter-day precision (n = 6) ranged 3.7% to 5.9% and 7.0% to 9.5%, respectively. The above results demonstrated that the MSPE combined with LC-MS/MS method was accurate and effective for quantitative determination of bile acids from complex biological samples.

Preparation of phenyl-boronic acid polymeric monolith by initiator-free ring-opening polymerization for microextraction of sulfonamides prior to their determination by ultra-performance liquid chromatography-tandem mass spectrometry.

In this study, a novel phenyl-boronic acid polymeric monolith (PBAPM) in polyether ether ketone (PEEK) tube was fabricated. The inner wall of PEEK tube was modified with mussel inspired polydopamine layer to firmly bond PBAPM, so as to avoid the outflow of PBAPM from PEEK tube and improve the service life and application scope of PBAPM. The PBAPM was synthesized by initiator-free ring-opening polymerization based on our previous work. The boric acid groups provided B-N coordination sites, as well as the hydrophobic amino and epoxy monomers provided hydrophobic interaction sites. Due to the synergistic effect of hydrophobic interaction and B-N coordination, the PBAPM exhibited excellent binding amounts for nitrogen-containing sulfonamides (SAs). In addition, the PBAPM possessed excellent stability, rigidity and permeability. Therefore, the PBAPM was used as solid phase microextraction (SPME) material for enrichment and separation of SAs from aqueous samples. The PBAPM SPME was optimized in detail, and combined with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis for simultaneous determination of 10 kinds of SAs from tap, lake and river water. Using only 1 mL of water samples, limit of quantitation of SAs could reach 0.54-4.5 ng L-1. Recoveries of standard spiked SAs from water samples were between 82.0% and 105.4%, with intra-day and inter-day relative standard deviation ranging from 3.3% to 5.6% and 4.2% to 8.1%, respectively. The PBAPM SPME combined with UPLC-MS/MS method shown better or similar recoveries, and used fewer samples than previous methods. These results demonstrated that the PBAPM could selectively separate and enrich ultra-trace nitrogen-containing SAs from aqueous samples.

Recent developments of molecularly imprinted polymer in CEC.

This review focuses on developments in the field of molecularly imprinted polymer (MIP) for CEC since August 2006. New technique of CEC-based MIP, e.g. covalent approach through the formation of Schiff base, miniemulsion polymerization, non-hydrolytic sol-gel methodology, MIP-derivatized silica monolithic column, are discussed from the view of MIP preparation. Some thoughts on potential future directions are also expressed in this review.

Preparation of phenyl-boronic acid polymer monolith by initiator-free ring-opening polymerization for microextraction of sulfamethoxazole and trimethoprim from animal-originated foodstuffs.

Boronate affinity materials are usually used for selective enrichment of cis-diol-containing compounds, mainly based on formation of pH-dependent cyclic ester between cis-diol and boronic acid. Recently, B-N coordination, or combined with hydrogen-bonding interaction, was employed as primary interaction for the extraction of nitrogen-containing compounds. However, there are no reports about the combination of hydrophobic (or π-π) interaction and B-N coordination for the extraction. Here, we prepared a novel hydrophobic phenyl-boronic acid polymer (PBAP) through initiator-free ring-opening polymerization. The adsorption experiment indicated that the PBAP could combine hydrophobic (or π-π) interaction and B-N coordination to enhance their adsorption capacity toward hydrophobic and nitrogen-containing compounds, for example sulfamethoxazole (SMX) and trimethoprim (TMP). In addition, the PBAP monolith synthesized in pipette tip was used as solid phase microextraction (SPME) sorbent with combination of ultra high performance liquid chromatography to extract and monitor SMX and TMP from animal-originated foodstuffs. The proposed method exhibited low limit of quantitation as 5.0 and 1.0 ng mL-1 for SMX and TMP, respectively. The recoveries at three spiked levels were between 92.4% to 100.5% for SMX, and 92.7% to 102.6% for TMP, with intra-day and inter-day relative standard deviations no more than 5.3% and 8.6%, respectively. These results well demonstrated that the combination of hydrophobic (or π-π) interaction and B-N coordination played an important role in the extraction of hydrophobic and nitrogen-containing compounds.

Cisplatin and curcumin co-loaded nano-liposomes for the treatment of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) continues to be a leading cause of cancer related death in the world. Conventional chemotherapeutic agents such as cisplatin (CDDP) have an unsatisfactory efficacy on HCC due to the poor response, severe toxicity and drug resistance. Curcumin (CUR) could improve the chemosensitivity of HCC to chemotherapy drugs by regulating a variety of signaling pathways. Herein, we describe a combination strategy using co-loaded liposomes to effectively deliver and release CDDP and curcumin (CUR) to HCC for overcoming the unsatisfactory clinical outcome of CDDP monotherapy. In the study, CDDP and CUR co-loaded liposomes (CDDP/CUR-Lip) were prepared by a reverse microemulsion and film dispersion method and their average particle size 294.6 ±â€¯14.8 nm with uniform size distribution. In vitro study showed that the nano sized CDDP/CUR-Lip could synchronously release both CDDP and CUR to achieve the synergistic effect against HCC cells based on the optimal ratio (1:8) of both drugs. Compared with free drug or encapsulated mono-drug therapy, CDDP/CUR-Lip demonstrated the higher anti-tumor activity in vitro against HepG2 cells with the IC50 of 0.62 µM. In addition, CDDP/CUR-Lip also increased intracellular ROS level during the HCC cells treatment. Furthermore, compared with single drug formulation, CDDP/CUR-Lip showed the elongated retention time (t1/2 = 2.38 h) and improved antitumor effect in both mouse hepatoma H22 and human HCC HepG2 xenograft models with reduced side effects. In conclusion, CDDP/CUR-Lip provide an attractive and potential strategy to attain synergistic effect of CDDP and CUR for the treatment of HCC.

Synthesis of boronate-decorated polyethyleneimine-grafted porous layer open tubular capillaries for enrichment of polyphenols in fruit juices.

A combination between modification with porous layer and grafting of polyethyleneimine (PEI) on the inner face of capillary was for the first time developed for boronate affinity in-tube solid-phase microextraction (SPME) material to enhance the extraction capacity for cis-diol-containing polyphenols. The successful synthesis of boronate-decorated polyethyleneimine-grafted porous layer open tubular (BPPLOT) capillary was confirmed by scanning electron micrograph, Fourier transform-infrared spectra and absorption experiments. The porous layer, PEI and boronate affinity provided high specific surface area, more binding sites for boronate groups and specific selectivity of BPPLOT capillary, respectively. The maximum binding quantity of BPPLOT capillary greatly improved, and ranged from 143 to 170 µg m-1 for cis-diol-containing polyphenols (catechin, chlorogenic acid, caffeic acid and epicatechin). A green method based on boronate affinity in-tube SPME was developed for separation and enrichment polyphenols, and some parameters of in-tube SPME were optimized. After in-tube SPME, HPLC with UV detection was used for quantitative determination of polyphenols. Recoveries of standard spiked cis-diol-containing polyphenols from fruit juice were between 80.9% and 102%, with intra-day and inter-day coefficient of variation ranging from 4.8% to 7.3% and 5.0% to 8.6%, respectively. Conversely, recovery of non-cis-diol-containing ferulic acid was no greater than 3.0%. These results suggested that the BPPLOT capillary could effectively separate and enrich cis-diol-containing polyphenols from real samples.

[Development and application of artificial vertebral body].

Artificial vertebral body has achieved good results in treating spinal tumors, tuberculosis, fracture and other diseases. Currently, artificial vertebral body with variety of kinds and pros and cons, is generally divided into two types: fusion type and movable type. The former according to whether the height could be adjusted and strength of self-stability is divided into three types: support-fixed type, adjust-fixed type and self-fixed type. Whether the height of self-fixed type could be adjusted is dependent on structure of collar thread rotation. The latter is due to mobile device of ball-and-socket joints or hollow structures instead of the disc which retains the activity of the spine to some extent. Materials of artificial vertebral body include metals, ceramics, biomaterials, polymer composites and other materials. Titanium with a dominant role in the metal has developed to the third generation, but there are still defects such as poor surface bioactivity; ceramics with the representative of hydroxyapatite composite, magnetic bioceramics, polycrystalline alumina ceramics and so on, which have the defects of processing complex and uneven mechanical properties; biological material is mainly dominated by xenogeneic bone, which is closest to human bone in structure and properties, but has defects of low toughness and complex production; polymer composites according to biological characteristics in general consists of biodegradable type and non-biodegradable type which are respectively represented by poly-lactide and polyethylene, each with advantages and disadvantages. Although the design and materials of prosthesis have made great progress, it is difficult to fully meet requirements of spinal implants and they need be further optimized. 3D printing technology makes process of the complex structure of prosthesis and individual customization possible and has broad development prospects. However, long production cycles and high cost of defect should be overcome. Although artificial vertebral body has achieved curative effect in treating spinal disease, there were reports of implant loosening or displacement. Combining with evaluation standards not unified, short follow-up time, its exact effect needs further observation.

NaCS-PDMDAAC immobilized cultivation of recombinant Dictyostelium discoideum for soluble human Fas ligand production.

Dictyostelium discoideum is a promising eukaryotic host for the expression of heterologous proteins requiring post-translational modifications. However, the dilute nature of D. discoideum cell culture limits applications for high value proteins production. D. discoideum cells, entrapped in sodium cellulose sulfate/poly-dimethyl-diallyl-ammonium chloride (NaCS-PDMDAAC) capsules were used for biosynthesis of the heterologous protein, soluble human Fas ligand (hFasL). Semi-continuous cultivations with capsules recycling were carried out in shake flasks. Also, a scaled-up cultivation of immobilized D. discoideum for hFasL production in a customized vitreous airlift bioreactor was conducted. The results show that NaCS-PDMDAAC capsules have desirable biophysical properties including biocompatibility with the D. discoideum cells and good mechanical stability throughout the duration of cultivation. A maximum cell density of 2.02 × 10(7) cells mL(-1) (equivalent to a maximum cell density of 2.22 × 10(8) cells mL(-1) in capsules) and a hFasL concentration of 130.40 µg L(-1) (equivalent to a hFasL concentration of 1434.40 µg L(-1) in capsules) were obtained in shake flask cultivation with capsules recycling. Also, a maximum cell density of 1.72 × 10(7) cells mL(-1) (equivalent to a maximum cell density of 1.89 × 10(8) cells mL(-1) in capsules) and a hFasL concentration of 106.10 µg L(-1) (equivalent to a hFasL concentration of 1167.10 µg L(-1) in capsules) were obtained after ∼170 h cultivation in the airlift bioreactor (with a working volume of 200 mL in a 315 mL bioreactor). As the article presents a premier work in the application of NaCS-PDMDAAC immobilized D. discoideum cells for the production of hFasL, more work is required to further optimize the system to generate higher cell densities and hFasL titers for large-scale applications.

Amphiphilic glycopolymer nanoparticles as vehicles for nasal delivery of peptides and proteins.

Nasal drug delivery system has been a very promising route for delivery of proteins and peptides for the reason that it can avoid degradation in gastrointestinal tract and metabolism by liver enzymes. However, the bioavailability of proteins and peptides is still low due to the rapid clearance of mucociliary. Here, to prolong the residence time of drugs and improve their absorption, we prepared amphiphilic glycopolymer poly(2-lactobionamidoethyl methacrylate-random-3-acrylamidophenylboronic acid) (p(LAMA-r-AAPBA), and the glycopolymer could assemble into the nanoparticles with narrow size distribution. Insulin, as a model drug, was efficiently encapsulated within the nanoparticles, and loading capacity was up to 12%. In vitro study revealed that the insulin release could be controlled by modifying the composition of glycopolymers. Cell viability showed that p(LAMA-r-AAPBA) nanoparticles had good cytocompatibility. Moreover, the mechanism of nanoparticle internalization into Calu-3 cells was a combination mechanism of clathrin-mediated endocytosis and lipid raft/caveolae-mediated endocytosis. Importantly, there was a significant decrease in the blood glucose levels after the nasal administration of p(LAMA-r-AAPBA) nanoparticles to diabetic rats. Therefore, p(LAMA-r-AAPBA) glycopolymers have a potential application as a nasal delivery systems for proteins and peptides.

Three-dimensional CT angiography for the diagnosis and assessment of arteriovenous malformations in the oral and maxillofacial region.

OBJECTIVE: The purpose of this study was to evaluate the diagnostic performance of three-dimensional computed tomography angiography (3D-CTA) for arteriovenous malformations (AVMs) in the oral and maxillofacial region. MATERIALS AND METHODS: Sixty four-slice spiral CT angiography of oral or maxillofacial region was performed in 8 patients with surgically proven arteriovenous malformations. The morphologic features, size, location, boundary, and feeding and draining vessels of lesions were reviewed. RESULTS: AVMs in 5 patients were located in the soft tissues and 3 were in the mandible. CTA of all cases showed tangles of disorganized vessels with well-defined borders. The feeding and draining vessels were enlarged and tortuous. Four patients had bone involvement. CONCLUSION: Sixty four-slice spiral CTA can accurately demonstrate the morphological characteristics of AVMs.

Molecularly imprinted polymers as a tool for separation in CEC.

Molecularly imprinted polymers (MIPs) are synthesized in the presence of a template which results in the formation of specific recognition cavities complementary to the template in shape and chemical functionality. One of the most successful application areas of MIPs is chromatographic sorbents, which are tailor-made synthetic polymers for a given analyte. However, low efficiency of MIP columns is often observed because of slow kinetics of the template. CEC-based MIPs are thought to improve efficiency of MIP-based separation due to the enhanced flow dynamics of CEC. Another attractive feature is the miniaturized format of CEC, so that fewer templates or monomers for the molecular imprinting are consumed, a characteristic desired for 'green chemistry'. The small dimensions of a capillary demand the development of novel polymer formats that can be applied to a miniaturized system. This review discusses the various formats, i.e., the micro- or nanoparticle, the coating and the monolith, for application in CEC as well as the use in MIP syntheses and characteristics.

Recognition of oxytocin by capillary electrochromatography with monolithic tetrapeptide-imprinted polymer used as the stationary phase.

Using YPLG (Tyr-Pro-Leu-Gly), a tetrapeptide, as the template, an imprinted monolithic column was prepared and applied to the selective recognition of oxytocin based on the epitope approach and capillary electrochromatography (CEC). By optimizing the polymerization solution in terms of functional monomer, cross-linking reagent, porogen, and imprinted template via CEC evaluations of synthesized columns, an imprinted monolith with good recognition capacity (the imprinting factors for YPLG and oxytocin were 4.499 and 4.013, respectively) and high column efficiency (theoretical plates for YPLG and oxytocin were 22,995 plates/m and 16,952 plates/m, respectively) was achieved. In addition, the effects of various experimental parameters on the recognition of oxytocin, including the organic modifier content, the buffer concentration, and the pH value, were studied systematically. Furthermore, a mixture of oxytocin and other proteins was analyzed using this monolithic CEC column, and oxytocin was eluted much more slowly than other large biomolecules, which demonstrated the high selective recognition ability of such an imprinted monolith for oxytocin with PLG (Pro-Leu-Gly) as the epitope. Figure Separation of a mixture of oxytocin, BSA, bovine hemoglobin, ovalbumin, and lysozyme on the open column, the blank monolithic column, and the monolithic YPLG-imprinted column.