The Role of Carbohydrate in Pharmaceuticals, Vaccines and Delivery Systems

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 31 July 2024 | Viewed by 11043

Special Issue Editors

Research Advisor, Institute for Research in Immunology and Cancer, Université de Montréal, Montreal, QC H3C 3P8, Canada
Interests: medicinal chemistry; carbohydrate chemistry; drug delivery
Department of Chemistry, Université du Quebéc à Montréal, P.O. Box 8888, Succ. Centre-Ville, Montreal, QC H3C 3P8, Canada
Interests: carbohydrate chemistry; vaccines; dendrimers
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Special Issue Information

Dear Colleagues,

This Special Issue of Pharmaceutics has been dedicated to the role of carbohydrates as therapeutic agents, vaccines, and delivery systems. Recent trends in carbohydrate chemistry are indicating their importance in medicinal chemistry in terms of key players for the treatment of a wide range of diseases, including immuno-oncology. Glycans on their own can be therapeutic targets as well as being biocompatible and nontoxic carriers in nanoparticle (NP) platforms to deliver therapeutical agents to biological targets.. Nanoscale multimeric glycans such as glycoliposomes, glycopolymers, and glycodendrimers are being fully exploited as new-generation phramaceuticals. Glycoinhibitors of enzymes involved in lysosomal storage diseases also constitute therapeutic targets of great value.

Carbohydrates, with their stereochemical richness and varied functionalities, are considered valuable for the treatment of bacterial and viral infections and constitute potent glycopharmaceutics. The recent development of glycan microarrays has also been a determinant for the more subtle identification of cancer markers and better selection of anticarbohydrate antibodies and lectins. Antibody–drug conjugates (ADCs) are of therapeutic importance provided that their glycans are properly engineered.

Dr. Leila Mousavifar
Prof. Dr. René Roy
Guest Editors

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Keywords

  • carbohydrates
  • vaccines
  • lectins
  • antibodies
  • galactins
  • cancer therapy
  • infectious diseases
  • nanoparticles
  • drug delivery
  • polymeric scaffold
  • drug delivery
  • medicinal chemistry
  • liposomes
  • immune system
  • drug uptake
  • neoglycolipides
  • Janus liposomes
  • glycosylated NPs
  • glycodendrimers

Published Papers (7 papers)

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Research

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19 pages, 4878 KiB  
Article
Carbohydrate Core–Shell Electrosprayed Microcapsules for Enhanced Oxidative Stability of Vitamin A Palmitate
by Elnaz Z. Fallahasghari, Marie Højgaard Lynge, Emma Espholin Gudnason, Kristin Munkerup, Ana C. Mendes and Ioannis S. Chronakis
Pharmaceutics 2023, 15(11), 2633; https://doi.org/10.3390/pharmaceutics15112633 - 16 Nov 2023
Cited by 2 | Viewed by 837
Abstract
Vitamin A is an essential micronutrient that is readily oxidized. In this study, the encapsulation of vitamin A palmitate (AP) within a core–shell carbohydrate matrix by co-axial electrospray and its oxidative stability was evaluated. The electrosprayed core–shell microcapsules consisted of a shell of [...] Read more.
Vitamin A is an essential micronutrient that is readily oxidized. In this study, the encapsulation of vitamin A palmitate (AP) within a core–shell carbohydrate matrix by co-axial electrospray and its oxidative stability was evaluated. The electrosprayed core–shell microcapsules consisted of a shell of octenyl succinic anhydride (OSA) modified corn starch, maltose (Hi-Cap), and a core of ethyl cellulose–AP (average diameter of about 3.7 µm). The effect of different compounds (digestion-resistant maltodextrin, soy protein hydrolysate, casein protein hydrolysate, and lecithin) added to the base core–shell matrix formulation on the oxidative stability of AP was investigated. The oxidative stability of AP was evaluated using isothermal and non-isothermal differential scanning calorimetry (DSC), and Raman and Attenuated Total Reflectance–Fourier Transform Infrared (ATR-FTIR) spectroscopy methods. The core–shell carbohydrate matrix minimizes the amount of AP present at the microparticle surface, thus protecting AP from oxidation. Furthermore, the most effective oxidation protection was achieved when casein protein hydrolysate was added to the core of the microcapsule due to hydrophobic and hydrogen bond interactions with AP and by the resistant maltodextrin in the shell, which acted as a filler. The utilization of ethanol as a solvent for the dispersion of the core compounds increased the hydrophobicity of the hydrolyzed proteins and contributed to the enhancement of their antioxidant ability. Both the carbohydrate core–shell microcapsule prepared by co-axial electrospray and the addition of oxidation protection compounds enhance the oxidative stability of the encapsulated AP. Full article
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17 pages, 2749 KiB  
Article
The Use of a Barley-Based Well to Define Cationic Betaglucan to Study Mammalian Cell Toxicity Associated with Interactions with Biological Structures
by Malgorzata Tymecka, Katarzyna Hac-Wydro, Magdalena Obloza, Piotr Bonarek and Kamil Kaminski
Pharmaceutics 2023, 15(7), 2009; https://doi.org/10.3390/pharmaceutics15072009 - 23 Jul 2023
Cited by 1 | Viewed by 875
Abstract
Among potential macromolecule-based pharmaceuticals, polycations seem particularly interesting due to their proven antimicrobial properties and use as vectors in gene therapy. This makes an understanding of the mechanisms of these molecules’ interaction with living structures important, so the goal of this paper was [...] Read more.
Among potential macromolecule-based pharmaceuticals, polycations seem particularly interesting due to their proven antimicrobial properties and use as vectors in gene therapy. This makes an understanding of the mechanisms of these molecules’ interaction with living structures important, so the goal of this paper was to propose and carry out experiments that will allow us to characterize these phenomena. Of particular importance is the question of toxicity of such structures to mammalian cells and, in the work presented here, two lines, normal fibroblasts 3T3-L1 and A549 lung cancer, were used to determine this. In this work, three well-defined cationic derivatives of barley-derived betaglucans obtained in a reaction with glycidyltrimethylammonium chloride (BBGGTMAC) with different degrees of cationization (50, 70, and 100% per one glucose unit) and electrostatic charge were studied. The studies address interactions of these polymers with proteins (bovine serum proteins and BSA), nucleic acids (DNA), glycosaminoglycans (heparin), and biological membranes. The results described in this study make it possible to indicate that toxicity is most strongly influenced by interactions with biological membranes and is closely related to the electrostatic charge of the macromolecule. The presentation of this observation was the goal of this publication. This paper also shows, using fluorescently labeled variants of polymers, the penetration and impact on cell structure (only for the polymer with the highest substitution binding to cell membranes is observed) by using confocal and SEM (for the polymer with the highest degree of substitution, and the appearance of additional structures on the surface of the cell membrane is observed). The labeled polymers are also tools used together with dynamic light scattering and calorimetric titration to study their interaction with other biopolymers. As for the interactions with biological membranes, lipid Langmuir monolayers as model membrane systems were used. Full article
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14 pages, 4263 KiB  
Article
Intraoral Drug Delivery: Highly Thiolated κ-Carrageenan as Mucoadhesive Excipient
by Gergely Kali, Andrea Fürst, Nuri Ari Efiana, Aida Dizdarević and Andreas Bernkop-Schnürch
Pharmaceutics 2023, 15(7), 1993; https://doi.org/10.3390/pharmaceutics15071993 - 20 Jul 2023
Cited by 2 | Viewed by 1437
Abstract
Aim: This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems. Methods: Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via 1H NMR, [...] Read more.
Aim: This study aims to design a novel thiolated κ-carrageenan (κ-CA-SH) and evaluate its potential as an excipient for the design of mucoadhesive drug delivery systems. Methods: Native κ-carrageenan (κ-CA) was thiolated with phosphorous pentasulfide in sulfolane and characterized via 1H NMR, FTIR, as well as Ellman’s test. Cytotoxicity was assessed via resazurin assay. In vitro release of the model drug, benzydamine hydrochloride, was determined. Tensile and mucosal residence time studies were performed on buccal and small intestinal mucosa. Mucoadhesive features were investigated via rheological studies with freshly isolated porcine mucus. Results: Thiolated κ-CA (κ-CA-SH) with 1213.88 ± 52 µmol/g thiol groups showed no cytotoxicity at a concentration of 1% (m/v) and low cytotoxicity up to 2% (m/v). Benzydamine hydrochloride showed slow release in solution for both polymers. Tensile studies on buccal and intestinal mucosa showed an up to 2.7-fold and 7.7-fold enhancement in the maximum detachment force (MDF) and total work of adhesion (TWA) of κ-CA-SH vs. κ-CA, respectively. The κ-CA-SH exhibited an up to 4.4-fold improved dynamic viscosity with mucus and significantly prolonged residence time on mucosa compared to native κ-CA. Conclusion: Since highly thiolated κ-CA shows a slow release of positively charged active pharmaceutical ingredients and enhanced mucoadhesive properties, it might be a promising excipient for local drug delivery in the oral cavity. Full article
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17 pages, 24222 KiB  
Article
Polysaccharide-Based Carriers for Pulmonary Insulin Delivery: The Potential of Coffee as an Unconventional Source
by Sara A. Valente, Guido R. Lopes, Isabel Ferreira, Miguel F. Galrinho, Margarida Almeida, Paula Ferreira, Maria T. Cruz, Manuel A. Coimbra and Cláudia P. Passos
Pharmaceutics 2023, 15(4), 1213; https://doi.org/10.3390/pharmaceutics15041213 - 11 Apr 2023
Cited by 1 | Viewed by 1415
Abstract
Non-invasive routes for insulin delivery are emerging as alternatives to currently painful subcutaneous injections. For pulmonary delivery, formulations may be in powdered particle form, using carriers such as polysaccharides to stabilise the active principle. Roasted coffee beans and spent coffee grounds (SCG) are [...] Read more.
Non-invasive routes for insulin delivery are emerging as alternatives to currently painful subcutaneous injections. For pulmonary delivery, formulations may be in powdered particle form, using carriers such as polysaccharides to stabilise the active principle. Roasted coffee beans and spent coffee grounds (SCG) are rich in polysaccharides, namely galactomannans and arabinogalactans. In this work, the polysaccharides were obtained from roasted coffee and SCG for the preparation of insulin-loaded microparticles. The galactomannan and arabinogalactan-rich fractions of coffee beverages were purified by ultrafiltration and separated by graded ethanol precipitations at 50% and 75%, respectively. For SCG, galactomannan-rich and arabinogalactan-rich fractions were recovered by microwave-assisted extraction at 150 °C and at 180 °C, followed by ultrafiltration. Each extract was spray-dried with insulin 10% (w/w). All microparticles had a raisin-like morphology and average diameters of 1–5 µm, which are appropriate for pulmonary delivery. Galactomannan-based microparticles, independently of their source, released insulin in a gradual manner, while arabinogalactan-based ones presented a burst release. The microparticles were seen to be non-cytotoxic for cells representative of the lung, specifically lung epithelial cells (A549) and macrophages (Raw 264.7) up to 1 mg/mL. This work shows how coffee can be a sustainable source of polysaccharide carriers for insulin delivery via the pulmonary route. Full article
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18 pages, 3690 KiB  
Article
Approaches to Assure Similarity between Pharmaceutical Heparins from Two Different Manufacturers
by Francisco Felipe Bezerra, Stephan N.M.C.G. Oliveira, Rodrigo A. Sales, Adriana A. Piquet, Nina V. Capillé, Eduardo Vilanova, Ana M.F. Tovar and Paulo A.S. Mourão
Pharmaceutics 2023, 15(4), 1115; https://doi.org/10.3390/pharmaceutics15041115 - 31 Mar 2023
Cited by 2 | Viewed by 979
Abstract
Pharmaceutical heparins from different manufacturers may present heterogeneities due to particular extraction and purification procedures or even variations in the raw material manipulation. Heparins obtained from different tissues also differ in their structure and activity. Nevertheless, there is an increased demand for more [...] Read more.
Pharmaceutical heparins from different manufacturers may present heterogeneities due to particular extraction and purification procedures or even variations in the raw material manipulation. Heparins obtained from different tissues also differ in their structure and activity. Nevertheless, there is an increased demand for more accurate assessments to ensure the similarities of pharmaceutical heparins. We propose an approach to accurately assess the similarity of these pharmaceutical preparations based on well-defined criteria, which are verified with a variety of refined analytical methods. We evaluate six commercial batches from two different manufacturers which were formulated with Brazilian or Chinese active pharmaceutical ingredients. Biochemical and spectroscopic methods and analysis based on digestion with heparinases were employed to evaluate the purity and structure of the heparins. Specific assays were employed to evaluate the biological activity. We observed minor but significant differences between the constitutive units of the heparins from these two manufacturers, such as the content of N-acetylated α-glucosamine. They also have minor differences in their molecular masses. These physicochemical differences have no impact on the anticoagulant activity but can indicate particularities on their manufacturing processes. The protocol we propose here for analyzing the similarity of unfractionated heparins is analogous to those successfully employed to compare low-molecular-weight heparins. Full article
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21 pages, 5873 KiB  
Article
Insightful Improvement in the Design of Potent Uropathogenic E. coli FimH Antagonists
by Leila Mousavifar, Meysam Sarshar, Clarisse Bridot, Daniela Scribano, Cecilia Ambrosi, Anna Teresa Palamara, Gérard Vergoten, Benoît Roubinet, Ludovic Landemarre, Julie Bouckaert and René Roy
Pharmaceutics 2023, 15(2), 527; https://doi.org/10.3390/pharmaceutics15020527 - 04 Feb 2023
Cited by 3 | Viewed by 2088
Abstract
Selective antiadhesion antagonists of Uropathogenic Escherichia coli (UPEC) type-1 Fimbrial adhesin (FimH) are attractive alternatives for antibiotic therapies and prophylaxes against acute or recurrent urinary tract infections (UTIs) caused by UPECs. A rational small library of FimH antagonists based on previously described C [...] Read more.
Selective antiadhesion antagonists of Uropathogenic Escherichia coli (UPEC) type-1 Fimbrial adhesin (FimH) are attractive alternatives for antibiotic therapies and prophylaxes against acute or recurrent urinary tract infections (UTIs) caused by UPECs. A rational small library of FimH antagonists based on previously described C-linked allyl α-D-mannopyranoside was synthesized using Heck cross-coupling reaction using a series of iodoaryl derivatives. This work reports two new members of FimH antagonist amongst the above family with sub nanomolar affinity. The resulting hydrophobic aglycones, including constrained alkene and aryl groups, were designed to provide additional favorable binding interactions with the so-called FimH “tyrosine gate”. The newly synthesized C-linked glycomimetic antagonists, having a hydrolytically stable anomeric linkage, exhibited improved binding when compared to previously published analogs, as demonstrated by affinity measurement through interactions by FimH lectin. The crystal structure of FimH co-crystallized with one of the nanomolar antagonists revealed the binding mode of this inhibitor into the active site of the tyrosine gate. In addition, selected mannopyranoside constructs neither affected bacterial growth or cell viability nor interfered with antibiotic activity. C-linked mannoside antagonists were effective in decreasing bacterial adhesion to human bladder epithelial cells (HTB-9). Therefore, these molecules constituted additional therapeutic candidates’ worth further development in the search for potent anti-adhesive drugs against infections caused by UPEC. Full article
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Review

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24 pages, 2710 KiB  
Review
Versatility of Liposomes for Antisense Oligonucleotide Delivery: A Special Focus on Various Therapeutic Areas
by Raghav Gupta, Sagar Salave, Dhwani Rana, Bharathi Karunakaran, Arun Butreddy, Derajram Benival and Nagavendra Kommineni
Pharmaceutics 2023, 15(5), 1435; https://doi.org/10.3390/pharmaceutics15051435 - 08 May 2023
Cited by 8 | Viewed by 2524
Abstract
Nucleic acid therapeutics, specifically antisense oligonucleotides (ASOs), can effectively modulate gene expression and protein function, leading to long-lasting curative effects. The hydrophilic nature and large size of oligonucleotides present translational challenges, which have led to the exploration of various chemical modifications and delivery [...] Read more.
Nucleic acid therapeutics, specifically antisense oligonucleotides (ASOs), can effectively modulate gene expression and protein function, leading to long-lasting curative effects. The hydrophilic nature and large size of oligonucleotides present translational challenges, which have led to the exploration of various chemical modifications and delivery systems. The present review provides insights into the potential role of liposomes as a drug delivery system for ASOs. The potential benefits of liposomes as an ASO carrier, along with their method of preparation, characterization, routes of administration, and stability aspects, have been thoroughly discussed. A novel perspective in terms of therapeutic applications of liposomal ASO delivery in several diseases such as cancer, respiratory disease, ophthalmic delivery, infectious diseases, gastrointestinal disease, neuronal disorders, hematological malignancies, myotonic dystrophy, and neuronal disorders remains the major highlights of this review. Full article
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