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Macromolecular Drug Delivery Vehicles
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Macromolecular Drug Delivery Vehicles

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Macromolecular Chemistry".

Deadline for manuscript submissions: closed (31 January 2021) | Viewed by 16968

Special Issue Editors

Dr. Nikolay Polyakov

E-Mail Website
Guest Editor
Institute of Chemical Kinetics and Combustion, Russian Academy of Sciences, 630090 Novosibirsk, Russia
Interests: carotenoids; drug delivery systems; spin chemistry; free radicals; antioxidant activity; electron transfer; membrane biophysics
Special Issues, Collections and Topics in MDPI journals
Dr. Adriana Trapani

E-Mail Website
Guest Editor
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, 70125 Bari, Italy
Interests: polymers; high molecular weight lipids; micro- and nano-carriers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The Special Issue entitled “Macromolecular Drug Delivery Vehicles” aims at covering recent advances concerning the administration of drugs, natural active principles, and organic and inorganic compounds via the use of high molecular weight excipients such as micelles, polymers, olygomers, lipids and biomaterials. Therefore, the supply of active principles is intended to be achieved by adopting chemical or biological entities whose molecular weight is higher than 1000 g/mol, In this context, the issue is conceived as a forum for presentation of rigorous research, reviews, and communications relevant to all aspects of vectorization of selected active substances, including the preparation, properties, and applications of the resulting high molecular weight carrier. Interfacial phenomena investigated by some of the abovementioned carriers are also included in the topics of the issue once they are in relation to systems of biological origin, having particular relevance to the medical, pharmaceutical and biotechnological fields.

Concerning the endpoints of the obtained drug delivery carrier, diagnosis, prevention or therapeutic purposes are to be matched in order to have significant consequences in terms of human or veterinary health. Finally, the role of the well-characterized vehicle must be the major proportion of the work reported, not a peripheral topic.

Dr. Nikolay Polyakov
Dr. Adriana Trapani
Guest Editors

Manuscript Submission Information

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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. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Polymers
  • Micelles
  • High molecular weight lipids
  • Polymeric conjugates
  • Micro- and nanocarriers
  • DNA/RNA vectorization
  • Membrane permeability

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Published Papers (4 papers)

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Research

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20 pages, 3201 KiB  
Article
Solubility, Permeability, Anti-Inflammatory Action and In Vivo Pharmacokinetic Properties of Several Mechanochemically Obtained Pharmaceutical Solid Dispersions of Nimesulide
by Wei Wei, Veronica I. Evseenko, Mikhail V. Khvostov, Sergey A. Borisov, Tatyana G. Tolstikova, Nikolay E. Polyakov, Aleksandr V. Dushkin, Wenhao Xu, Lu Min and Weike Su
Molecules 2021, 26(6), 1513; https://doi.org/10.3390/molecules26061513 - 10 Mar 2021
Cited by 15 | Viewed by 3958
Abstract
Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the [...] Read more.
Nimesulide (NIM, N-(4-nitro-2-phenoxyphenyl)methanesulfonamide) is a relatively new nonsteroidal anti-inflammatory analgesic drug. It is practically insoluble in water (<0.02 mg/mL). This very poor aqueous solubility of the drug may lead to low bioavailability. The objective of the present study was to investigate the possibility of improving the solubility and the bioavailability of NIM via complexation with polysaccharide arabinogalactan (AG), disodium salt of glycyrrhizic acid (Na2GA), hydroxypropyl-β-cyclodextrin (HP-β-CD) and MgCO3. Solid dispersions (SD) have been prepared using a mechanochemical technique. The physical properties of nimesulide SD in solid state were characterized by differential scanning calorimetry and X-ray diffraction studies. The characteristics of the water solutions which form from the obtained solid dispersions were analyzed by reverse phase and gel permeation HPLC. It was shown that solubility increases for all complexes under investigation. These phenomena are obliged by complexation with auxiliary substances, which was shown by 1H-NMR relaxation methods. The parallel artificial membrane permeability assay (PAMPA) was used for predicting passive intestinal absorption. Results showed that mechanochemically obtained complexes with polysaccharide AG, Na2GA, and HP-β-CD enhanced permeation of NIM across an artificial membrane compared to that of the pure NIM. The complexes were examined for anti-inflammatory activity on a model of histamine edema. The substances were administered per os to CD-1 mice. As a result, it was found that all investigated complexes dose-dependently reduce the degree of inflammation. The best results were obtained for the complexes of NIM with Na2GA and HP-β-CD. In noted case the inflammation can be diminished up to 2-fold at equal doses of NIM. Full article
(This article belongs to the Special Issue Macromolecular Drug Delivery Vehicles)
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12 pages, 3035 KiB  
Article
pH-Sensitive Glycyrrhizin Based Vesicles for Nifedipine Delivery
by Olga Yu. Selyutina, Anna V. Mastova, Ekaterina A. Shelepova and Nikolay E. Polyakov
Molecules 2021, 26(5), 1270; https://doi.org/10.3390/molecules26051270 - 26 Feb 2021
Cited by 16 | Viewed by 2919
Abstract
Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to [...] Read more.
Glycyrrhizic acid, or glycyrrhizin (GA), a major active component of licorice root, has been widely used in traditional Chinese and Japanese medicine since ancient times. However, only in the last decades has a novel and unusual property of the GA been discovered to form water-soluble, supramolecular complexes with a variety of lipophilic drugs. These complexes show significant advantages over other known delivery systems, in particular, due to strong pH sensitivity, the properties of GA self-associates. In the present study, a supramolecular complex formation of the hypotensive and antiarrhythmic drug nifedipine with GA has been studied at different pH values, corresponding to the different degrees of GA dissociation, including a fully dissociated state of GA. Both NMR experiments and molecular dynamics simulations demonstrate the existence of the nifedipine complex with GA at all dissociation states of GA. However, optical absorption experiments show the decrease of complex stability and solubility at pH > 6 when the GA molecule is fully deprotonated. It means the higher release rate of the drug in a neutral and basic environment compared with acid media. These results could form the basis of follow-up studies of GA self-associates as pH-controlled drug delivery systems. Full article
(This article belongs to the Special Issue Macromolecular Drug Delivery Vehicles)
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19 pages, 3585 KiB  
Article
Cyto/Biocompatibility of Dopamine Combined with the Antioxidant Grape Seed-Derived Polyphenol Compounds in Solid Lipid Nanoparticles
by Adriana Trapani, Lorenzo Guerra, Filomena Corbo, Stefano Castellani, Enrico Sanna, Loredana Capobianco, Anna Grazia Monteduro, Daniela Erminia Manno, Delia Mandracchia, Sante Di Gioia and Massimo Conese
Molecules 2021, 26(4), 916; https://doi.org/10.3390/molecules26040916 - 9 Feb 2021
Cited by 35 | Viewed by 3445
Abstract
Background: The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the [...] Read more.
Background: The loss of nigrostriatal neurons containing dopamine (DA) together with the “mitochondrial dysfunction” in midbrain represent the two main causes related to the symptoms of Parkinson’s disease (PD). Hence, the aim of this investigation is to co-administer the missing DA and the antioxidant grape seed-derived proanthocyanidins (grape seed extract, GSE) in order to increase the levels of the neurotransmitter (which is unable to cross the Blood Brain Barrier) and reducing the oxidative stress (OS) related to PD, respectively. Methods: For this purpose, we chose Solid Lipid Nanoparticles (SLN), because they have been already proven to increase DA uptake in the brain. DA-SLN adsorbing GSE (GSE/DA-SLN) were formulated and subjected to physico-chemical characterization, and their cytocompatibility and protection against OS were examined. Results: GSE was found on SLN surface and release studies evidenced the efficiency of GSE in preventing DA autoxidation. Furthermore, SLN showed high mucoadhesive strength and were found not cytotoxic to both primary Olfactory Ensheathing and neuroblastoma SH-SY5Y cells by MTT test. Co-administration of GSE/DA-SLN and the OS-inducing neurotoxin 6-hydroxydopamine (100 μM) resulted in an increase of SH-SY5Y cell viability. Conclusions: Hence, SLN formulations containing DA and GSE may constitute interesting candidates for non-invasive nose-to-brain delivery. Full article
(This article belongs to the Special Issue Macromolecular Drug Delivery Vehicles)
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Review

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19 pages, 3317 KiB  
Review
Factors Affecting Extracellular Vesicles Based Drug Delivery Systems
by Isha Gaurav, Abhimanyu Thakur, Ashok Iyaswamy, Xuehan Wang, Xiaoyu Chen and Zhijun Yang
Molecules 2021, 26(6), 1544; https://doi.org/10.3390/molecules26061544 - 11 Mar 2021
Cited by 56 | Viewed by 5949
Abstract
Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted [...] Read more.
Extracellular vesicles (EVs) play major roles in intracellular communication and participate in several biological functions in both normal and pathological conditions. Surface modification of EVs via various ligands, such as proteins, peptides, or aptamers, offers great potential as a means to achieve targeted delivery of therapeutic cargo, i.e., in drug delivery systems (DDS). This review summarizes recent studies pertaining to the development of EV-based DDS and its advantages compared to conventional nano drug delivery systems (NDDS). First, we compare liposomes and exosomes in terms of their distinct benefits in DDS. Second, we analyze what to consider for achieving better isolation, yield, and characterization of EVs for DDS. Third, we summarize different methods for the modification of surface of EVs, followed by discussion about different origins of EVs and their role in developing DDS. Next, several major methods for encapsulating therapeutic cargos in EVs have been summarized. Finally, we discuss key challenges and pose important open questions which warrant further investigation to develop more effective EV-based DDS. Full article
(This article belongs to the Special Issue Macromolecular Drug Delivery Vehicles)
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