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Advanced Pharmaceutical Polymers

A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Biobased and Biodegradable Polymers".

Deadline for manuscript submissions: closed (25 September 2023) | Viewed by 11340

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Guest Editor
School of Pharmaceutical Sciences, Hainan University, Haikou, China
Interests: polysaccharide vaccine; novel conjugation chemistry; drug conjugates; carbohydrate biochemistry
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Special Issue Information

Dear Colleagues,

Polymers play essential roles in the pharmaceutical field, thanks to their superior bio-pharmaceutical and chemical-physical properties. In recent years, the advanced therapeutic treatments and the spreading of biological therapeutics have further encouraged the development of pharmaceutical polymers, thus bringing more opportunities for efficacious vaccines, drug delivery systems, pharmaceutical dosage forms, and diagnostics.

Within this framework, this Special Issue (SI) is focused on the application of naturally derived, modified, or synthetic polymers as either the active component or delivery vehicle in the pharmaceutical field. The scope of this SI is to provide an expert panel with a primary emphasis on addressing the needs and interests of both academic and industrial readers.

Prof. Dr. Chengli Zong
Guest Editor

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Polymers is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

  • polymer-based vaccines
  • macromolecular complex
  • natural polymers
  • synthetic polymers
  • bio-active polymers
  • nanomedicine
  • biomedical applications
  • medical devices

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Published Papers (4 papers)

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Research

13 pages, 4184 KiB  
Article
Unfolding Protein-Based Hapten Coupling via Thiol–Maleimide Click Chemistry: Enhanced Immunogenicity in Anti-Nicotine Vaccines Based on a Novel Conjugation Method and MPL/QS-21 Adjuvants
by Ying Xu, Huiting Li, Xiongyan Meng, Jing Yang, Yannan Xue, Changcai Teng, Wenxin Lv, Zhen Wang, Xiaodan Li, Tiantian Sun, Shuai Meng and Chengli Zong
Polymers 2024, 16(7), 931; https://doi.org/10.3390/polym16070931 - 28 Mar 2024
Viewed by 1442
Abstract
Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by [...] Read more.
Vaccines typically work by eliciting an immune response against larger antigens like polysaccharides or proteins. Small molecules like nicotine, on their own, usually cannot elicit a strong immune response. To overcome this, anti-nicotine vaccines often conjugate nicotine molecules to a carrier protein by carbodiimide crosslinking chemistry to make them polymeric and more immunogenic. The reaction is sensitive to conditions such as pH, temperature, and the concentration of reactants. Scaling up the reaction from laboratory to industrial scales while maintaining consistency and yield can be challenging. Despite various approaches, no licensed anti-nicotine vaccine has been approved so far due to the susboptimal antibody titers. Here, we report a novel approach to conjugate maleimide-modified nicotine hapten with a disulfide bond-reduced carrier protein in an organic solvent. It has two advantages compared with other approaches: (1) The protein was unfolded to make the peptide conformation more flexible and expose more conjugation sites; (2) thiol–maleimide “click” chemistry was utilized to conjugate the disulfide bond-reduced protein and maleimide-modified nicotine due to its availability, fast kinetics, and bio-orthogonality. Various nicotine conjugate vaccines were prepared via this strategy, and their immunology effects were investigated by using MPL and QS-21 as adjuvants. The in vivo study in mice showed that the nicotine–BSA conjugate vaccines induced high anti-nicotine IgG antibody titers, compared with vaccines prepared by using traditional condensation methods, indicating the success of the current strategy for further anti-nicotine or other small-molecule vaccine studies. The enhancement was more significant by using MPL and QS-21 than that of traditional aluminum adjuvants. Full article
(This article belongs to the Special Issue Advanced Pharmaceutical Polymers)
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10 pages, 7379 KiB  
Article
Self-Assembled TLR7/8 Agonist-Mannose Conjugate as An Effective Vaccine Adjuvant for SARS-CoV-2 RBD Trimer
by Changcai Teng, Xiongyan Meng, Yeqin Hu, Hongzhao Mao, Huiting Li, Jing Yang, Tiantian Sun, Shuai Meng and Chengli Zong
Polymers 2022, 14(24), 5466; https://doi.org/10.3390/polym14245466 - 13 Dec 2022
Cited by 4 | Viewed by 2186
Abstract
Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe [...] Read more.
Small synthetic TLR7/8-agonists can be used as vaccine adjuvants to enhance cell and humoral-mediated immune responses to specific antigens. Despite their potency, after local injection they can be dispersed to undesired body parts causing high reactogenicity, limiting their clinical applications. Here we describe a vaccination strategy that employs the covalent conjugate of a mannose and TLR7/8 agonist as a vaccine adjuvant to take advantage of mannose binding C-type lectins on dendritic cells to enhance the vaccine’s immunogenicity. The mannose-TLR7/8 agonist conjugate can self-assemble into nanoparticles with the hydrophilic mannose on the outside and hydrophobic TLR7/8 agonist inside. Although its ability to stimulate HEK-BlueTM hTLR7/8 cells dropped, it can efficiently stimulate mouse bone marrow-derived dendritic cells as indicated by the up-regulation of CD80 and CD86, and higher cytokine expression levels of TNF-α, IL6, and IL-12p70 than the native TLR7/8 agonist. In vivo, vaccination using the SARS-CoV-2 RBD trimer as the antigen and the conjugate as the adjuvant induced a significantly higher amount of IgG2a. These results suggest that the mannose-TLR7/8-agonist conjugate can be used as an effective vaccine adjuvant. Full article
(This article belongs to the Special Issue Advanced Pharmaceutical Polymers)
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10 pages, 1959 KiB  
Article
Characterization of High Molecular Weight Pneumococcal Conjugate by SEC-MALS and AF4-MALS
by James Z. Deng, Jason Lin, Michelle Chen, Catherine Lancaster and Ping Zhuang
Polymers 2022, 14(18), 3769; https://doi.org/10.3390/polym14183769 - 9 Sep 2022
Cited by 5 | Viewed by 3717
Abstract
Infections by Streptococcus pneumoniae can cause serious pneumococcal diseases and other medical complications among patients. Polysaccharide-based vaccines have been successfully developed as prophylactic agents against such deadly bacterial infections. In the 1980s, PNEUMOVAX® 23 were introduced as the first pneumococcal polysaccharide vaccines [...] Read more.
Infections by Streptococcus pneumoniae can cause serious pneumococcal diseases and other medical complications among patients. Polysaccharide-based vaccines have been successfully developed as prophylactic agents against such deadly bacterial infections. In the 1980s, PNEUMOVAX® 23 were introduced as the first pneumococcal polysaccharide vaccines (PPSV). Later, pneumococcal polysaccharides were conjugated to a carrier protein to improve immune responses. Pneumococcal conjugate vaccines (PCV) such as PREVNAR® and VAXNEUVANCE™ have been developed. Of the more than 90 pneumococcal bacteria serotypes, serotype 1 (ST-1) and serotype 4 (ST-4) are the two main types that cause invasive pneumococcal diseases (IPD) that could lead to morbidity and mortality. Development of a novel multi-valent PCV against these serotypes requires extensive biophysical and biochemical characterizations of each monovalent conjugate (MVC) in the vaccine. To understand and characterize these high molecular weight (Mw) polysaccharide protein conjugates, we employed the multi-angle light scattering (MALS) technique coupled with size-exclusion chromatography (SEC) separation and asymmetrical flow field flow fractionation (AF4). MALS analysis of MVCs from the two orthogonal separation mechanisms helps shed light on the heterogeneity in conformation and aggregation states of each conjugate. Full article
(This article belongs to the Special Issue Advanced Pharmaceutical Polymers)
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13 pages, 6525 KiB  
Article
Heparin Protects Severe Acute Pancreatitis by Inhibiting HMGB-1 Active Secretion from Macrophages
by Jing Yang, Xujiao Tang, Qingqing Wu, Panpan Ren, Yishu Yan, Wei Liu and Chun Pan
Polymers 2022, 14(12), 2470; https://doi.org/10.3390/polym14122470 - 17 Jun 2022
Cited by 4 | Viewed by 3210
Abstract
Heparin has shown benefits in severe acute pancreatitis (SAP) therapy, but the underlying mechanisms were unknown. Extracellular high-mobility group protein-1 (HMGB-1) has been regarded as a central mediator contributing to inflammation exacerbation and disease aggravation. We hypothesized heparin attenuated the disease by targeting [...] Read more.
Heparin has shown benefits in severe acute pancreatitis (SAP) therapy, but the underlying mechanisms were unknown. Extracellular high-mobility group protein-1 (HMGB-1) has been regarded as a central mediator contributing to inflammation exacerbation and disease aggravation. We hypothesized heparin attenuated the disease by targeting HMGB-1-related pathways. In the present study, the possible therapeutic roles of heparin and its non-anticoagulant derivatives, 6-O-desulfulted heparin and N-acylated-heparin, were determined on mouse models induced by “Two-Hit” of L-arginine. The compounds exhibited potent efficiency by substantially decreasing the pancreatic necrosis, macrophage infiltration, and serum inflammatory cytokine (IL-6 and TNF-α) concentration. Moreover, they greatly reduced the rapidly increasing extracellular HMGB-1 levels in the L-arginine injured pancreases. As a result, multiple organ failure and mortality of the mice were inhibited. Furthermore, the drugs were incubated with the RAW264.7 cells activated with damaged pancreatic tissue of SAP mice in vitro. They were found to inhibit HMGB-1 transfer from the nucleus to the plasma, a critical step during HMGB-1 active secretion from macrophages. The results were carefully re-examined with a caerulein and LPS induced mouse model, and similar results were found. The paper demonstrated heparin alleviated SAP independent of the anti-coagulant functions. Therefore, non-anticoagulant heparin derivatives might become promising approaches to treat patients suffering from SAP. Full article
(This article belongs to the Special Issue Advanced Pharmaceutical Polymers)
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