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Pharmaceutics
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Biodegradable Nanomaterials for Targeted Drug Delivery
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Biodegradable Nanomaterials for Targeted Drug Delivery

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

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 23654

Special Issue Editor

Prof. Dr. Andriy Grafov

E-Mail Website
Guest Editor
Materials Chemistry Division, Department of Chemistry, University of Helsinki, 00560 Helsinki, Finland
Interests: nanochemistry; ethnomedical pharmaceutically active compounds; drug; nanoformulation

Special Issue Information

Dear Colleagues,

Nanostructures for targeted drug delivery have attracted increasing attention owing to their ability to improve drug efficacy, enhance the bioavailability of active ingredients, control their release, or provide a possibility to target cells. However, nanomedicine is still at an early stage. Different forms of nanostructures have been used for active targeting based on biorecognition by particular cells beyond purely size-dependent biological and chemical interactions. The development of pharmaceutically active compounds (PhACs) modulating immune response is a challenge for modern medicine.

This volume will deal with many technical problems associated with the synthesis and composition of promising PhACs (including ethnomedical ones) and nano-assemblies containing them, molecular modeling of those systems and their interactions, their uptake into the target cell, efficient stimuli- triggered payload release, and their bioavailability, toxicity profiles, and immunomodulatory activity.

Prof. Dr. Andriy Grafov
Guest Editor

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Keywords

  • nanomedicine
  • bioavailability
  • nanoformulation
  • drug delivery
  • toxicity
  • immunomodulation
  • molecular simulations

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Published Papers (9 papers)

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Research

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15 pages, 4858 KiB  
Article
Synthesis, Characterization, and Biological Evaluation of Chitosan Nanoparticles Cross-Linked with Phytic Acid and Loaded with Colistin against Extensively Drug-Resistant Bacteria
by Fabian Pacheco, Alejandro Barrera, Yhors Ciro, Dorian Polo-Cerón, Constain H. Salamanca and José Oñate-Garzón
Pharmaceutics 2024, 16(9), 1115; https://doi.org/10.3390/pharmaceutics16091115 - 24 Aug 2024
Viewed by 1161
Abstract
The natural evolution of microorganisms, as well as the inappropriate use of medicines, have accelerated the problem of drug resistance to many of the antibiotics employed today. Colistin, a lipopeptide antibiotic used as a last resort against multi-resistant strains, has also begun to [...] Read more.
The natural evolution of microorganisms, as well as the inappropriate use of medicines, have accelerated the problem of drug resistance to many of the antibiotics employed today. Colistin, a lipopeptide antibiotic used as a last resort against multi-resistant strains, has also begun to present these challenges. Therefore, this study was focused on establishing whether colistin associated with chitosan nanoparticles could improve its antibiotic activity on an extremely resistant clinical isolate of Pseudomonas aeruginosa, which is a clinically relevant Gram-negative bacterium. For this aim, nanoparticulate systems based on phytic acid cross-linked chitosan and loaded with colistin were prepared by the ionic gelation method. The characterization included particle size, polydispersity index-PDI, and zeta potential measurements, as well as thermal (DSC) and spectrophotometric (FTIR) analysis. Encapsulation efficiency was assessed by the bicinchoninic acid (BCA) method, while the antimicrobial evaluation was made following the CLSI guidelines. The results showed that colistin-loaded nanoparticles were monodispersed (PDI = 0.196) with a particle size of around 266 nm and a positive zeta potential (+33.5 mV), and were able to associate with around 65.8% of colistin and decrease the minimum inhibitory concentration from 16 μg/mL to 4 μg/mL. These results suggest that the association of antibiotics with nanostructured systems could be an interesting alternative to recover the antimicrobial activity on resistant strains. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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15 pages, 3845 KiB  
Article
A Second Wind for Inorganic APIs: Leishmanicidal and Antileukemic Activity of Hydrated Bismuth Oxide Nanoparticles
by Andriy Grafov, Ana Flávia da Silva Chagas, Alice de Freitas Gomes, Wessal Ouedrhiri, Pierfrancesco Cerruti, Maria Cristina Del Barone, Breno de Souza Mota, Carlos Eduardo de Castro Alves, Anny Maíza Vargas Brasil, Antonia Maria Ramos Franco Pereira and Gemilson Soares Pontes
Pharmaceutics 2024, 16(7), 874; https://doi.org/10.3390/pharmaceutics16070874 - 29 Jun 2024
Viewed by 1107
Abstract
American cutaneous leishmaniasis is a disease caused by protozoa of the genus Leishmania. Currently, meglumine antimoniate is the first-choice treatment for the disease. The limited efficacy and high toxicity of the drug results in the necessity to search for new active principles. Nanotechnology [...] Read more.
American cutaneous leishmaniasis is a disease caused by protozoa of the genus Leishmania. Currently, meglumine antimoniate is the first-choice treatment for the disease. The limited efficacy and high toxicity of the drug results in the necessity to search for new active principles. Nanotechnology is gaining importance in the field, since it can provide better efficacy and lower toxicity of the drugs. The present study aimed to synthesize, characterize, and evaluate the in vitro leishmanicidal and antileukemic activity of bismuth nanoparticles (BiNPs). Promastigotes and amastigotes of L. (V.) guyanensis and L. (L.) amazonensis were exposed to BiNPs. The efficacy of the nanoparticles was determined by measurement of the parasite viability and the percentage of infected cells, while the cytotoxicity was characterized by the colorimetry. BiNPs did not induce cytotoxicity in murine peritoneal macrophages and showed better efficacy in inhibiting promastigotes (IC50 < 0.46 nM) and amastigotes of L. (L.) amazonensis. This is the first report on the leishmanicidal activity of Bi-based materials against L. (V.) guayanensis. BiNPs demonstrated significant cytotoxic activity against K562 and HL60 cells at all evaluated concentrations. While the nanoparticles also showed some cytotoxicity towards non-cancerous Vero cells, the effect was much lower compared to that on cancer cells. Treatment with BiNPs also had a significant effect on inhibiting and reducing colony formation in HL60 cells. These results indicate that bismuth nanoparticles have the potential for an inhibitory effect on the clonal expansion of cancer cells. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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23 pages, 1816 KiB  
Article
Formulation and Preparation of Losartan-Potassium-Loaded Controlled-Release Matrices Using Ethocel Grade 10 to Establish a Correlation between In Vitro and In Vivo Results
by Kamran Ahmad Khan, Ashfaq Ahmad, Carlotta Marini, Mario Nicotra, Alessandro Di Cerbo, Fazal-Ur-Rehman, Naveed Ullah and Gul Majid Khan
Pharmaceutics 2024, 16(2), 186; https://doi.org/10.3390/pharmaceutics16020186 - 28 Jan 2024
Viewed by 2543
Abstract
In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer w/w ratios (10:3, 10:4, and 10:5). The matrices were tested [...] Read more.
In the current study, matrices of losartan potassium were formulated with two different polymers (Ethocel 10 premium and Ethocel 10FP premium), along with a filler and a lubricant, at different drug-to-polymer w/w ratios (10:3, 10:4, and 10:5). The matrices were tested by the direct compression method, and their hardness, diameter, thickness, friability, weight variation, content uniformity, and in vitro dissolution tests were assessed to determine 24-h drug release rates. The matrices with Ethocel 10 FP at a 10:4 ratio exhibited pseudo-zero-order kinetics (n-value of 0.986), while the dissolution data of the test matrices and reference tablets did not match. The new test-optimized matrices were also tested in rabbits, and their pharmacokinetic parameters were investigated: half-life (11.78 ± 0.018 h), Tmax (2.105 ± 1.131 h), Cmax (205.98 ± 0.321 μg/mL), AUCo (5931.10 ± 1.232 μg·h/mL), AUCo-inf (7348.46 ± 0.234 μg·h/mL), MRTo-48h (17.34 ± 0.184 h), and Cl (0.002 ± 0.134 mL/min). A correlation value of 0.985 between the in vitro and in vivo results observed for the test-optimized matrices was observed, indicating a level-A correlation between the percentage of the drug released in vitro and the percentage of the drug absorbed in vivo. The matrices might improve patient compliance with once-a-day dosing and therapeutic outcomes. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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11 pages, 2021 KiB  
Article
One Step Purification—Vaccine Delivery System
by Ernesto R. Soto, Charles A. Specht, Chrono K. Lee, Stuart M. Levitz and Gary R. Ostroff
Pharmaceutics 2023, 15(5), 1390; https://doi.org/10.3390/pharmaceutics15051390 - 1 May 2023
Cited by 7 | Viewed by 1829
Abstract
Glucan particles (GPs) are hollow, porous 3–5 µm microspheres derived from the cell walls of Baker’s yeast (Saccharomyces cerevisiae). Their 1,3-β-glucan outer shell allows for receptor-mediated uptake by macrophages and other phagocytic innate immune cells expressing β-glucan receptors. GPs have been [...] Read more.
Glucan particles (GPs) are hollow, porous 3–5 µm microspheres derived from the cell walls of Baker’s yeast (Saccharomyces cerevisiae). Their 1,3-β-glucan outer shell allows for receptor-mediated uptake by macrophages and other phagocytic innate immune cells expressing β-glucan receptors. GPs have been used for the targeted delivery of a wide range of payloads, including vaccines and nanoparticles, encapsulated inside the hollow cavity of GPs. In this paper, we describe the methods to prepare GP-encapsulated nickel nanoparticles (GP-Ni) for the binding of histidine (His)-tagged proteins. His-tagged Cda2 cryptococcal antigens were used as payloads to demonstrate the efficacy of this new GP vaccine encapsulation approach. The GP-Ni-Cda2 vaccine was shown to be comparable to our previous approach utilizing mouse serum albumin (MSA) and yeast RNA trapping of Cda2 in GPs in a mouse infection model. This novel GP-Ni approach allows for the one-step binding of His-tagged vaccine antigens and encapsulation in an effective delivery vehicle to target vaccines to antigen-presenting cells (APCs), antigen discovery, and vaccine development. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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16 pages, 2538 KiB  
Article
Recombinant Proteins for Assembling as Nano- and Micro-Scale Materials for Drug Delivery: A Host Comparative Overview
by José Luis Corchero, Marianna T. P. Favaro, Merce Márquez-Martínez, Jara Lascorz, Carlos Martínez-Torró, Julieta M. Sánchez, Hèctor López-Laguna, Luís Carlos de Souza Ferreira, Esther Vázquez, Neus Ferrer-Miralles, Antonio Villaverde and Eloi Parladé
Pharmaceutics 2023, 15(4), 1197; https://doi.org/10.3390/pharmaceutics15041197 - 9 Apr 2023
Cited by 5 | Viewed by 2871
Abstract
By following simple protein engineering steps, recombinant proteins with promising applications in the field of drug delivery can be assembled in the form of functional materials of increasing complexity, either as nanoparticles or nanoparticle-leaking secretory microparticles. Among the suitable strategies for protein assembly, [...] Read more.
By following simple protein engineering steps, recombinant proteins with promising applications in the field of drug delivery can be assembled in the form of functional materials of increasing complexity, either as nanoparticles or nanoparticle-leaking secretory microparticles. Among the suitable strategies for protein assembly, the use of histidine-rich tags in combination with coordinating divalent cations allows the construction of both categories of material out of pure polypeptide samples. Such molecular crosslinking results in chemically homogeneous protein particles with a defined composition, a fact that offers soft regulatory routes towards clinical applications for nanostructured protein-only drugs or for protein-based drug vehicles. Successes in the fabrication and final performance of these materials are expected, irrespective of the protein source. However, this fact has not yet been fully explored and confirmed. By taking the antigenic RBD domain of the SARS-CoV-2 spike glycoprotein as a model building block, we investigated the production of nanoparticles and secretory microparticles out of the versions of recombinant RBD produced by bacteria (Escherichia coli), insect cells (Sf9), and two different mammalian cell lines (namely HEK 293F and Expi293F). Although both functional nanoparticles and secretory microparticles were effectively generated in all cases, the technological and biological idiosyncrasy of each type of cell factory impacted the biophysical properties of the products. Therefore, the selection of a protein biofabrication platform is not irrelevant but instead is a significant factor in the upstream pipeline of protein assembly into supramolecular, complex, and functional materials. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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23 pages, 6992 KiB  
Article
Electrospun Nanofibers Loaded with Plantago major L. Extract for Potential Use in Cutaneous Wound Healing
by Javier M. Anaya-Mancipe, Vanessa M. Queiroz, Rafael F. dos Santos, Rosane N. Castro, Verônica S. Cardoso, Alane B. Vermelho, Marcos L. Dias and Rossana M. S. M. Thiré
Pharmaceutics 2023, 15(4), 1047; https://doi.org/10.3390/pharmaceutics15041047 - 24 Mar 2023
Cited by 6 | Viewed by 3142
Abstract
Plantago major L. is a plant available worldwide that has been traditionally used for several medical applications due to its wound healing, anti-inflammatory, and antimicrobial properties. This work aimed to develop and evaluate a nanostructured PCL electrospun dressing with P. major extract encapsulated [...] Read more.
Plantago major L. is a plant available worldwide that has been traditionally used for several medical applications due to its wound healing, anti-inflammatory, and antimicrobial properties. This work aimed to develop and evaluate a nanostructured PCL electrospun dressing with P. major extract encapsulated in nanofibers for applications in wound healing. The extract from leaves was obtained by extraction in a mixture of water:ethanol = 1:1. The freeze-dried extract presented a minimum inhibitory concentration (MIC) for Staphylococcus Aureus susceptible and resistant to methicillin of 5.3 mg/mL, a high antioxidant capacity, but a low content of total flavonoids. Electrospun mats without defects were successfully produced using two P. major extract concentrations based on the MIC value. The extract incorporation in PCL nanofibers was confirmed using FTIR and contact angle measurements. The PCL/P. major extract was evaluated using DSC and TGA demonstrating that the incorporation of the extract decreases the thermal stability of the mats as well as the degree of crystallinity of PCL-based fibers. The P. major extract incorporation on electrospun mats produced a significant swelling degree (more than 400%) and increased the capacity of adsorbing wound exudates and moisture, important characteristics for skin healing. The extract-controlled release evaluated using in vitro study in PBS (pH, 7.4) shows that the P. major extract delivery from the mats occurs in the first 24 h, demonstrating their potential capacity to be used in wound healing. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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21 pages, 2673 KiB  
Article
Polylactic Acid/Poly(vinylpyrrolidone) Co-Electrospun Fibrous Membrane as a Tunable Quercetin Delivery Platform for Diabetic Wounds
by Francesca Di Cristo, Anna Valentino, Ilenia De Luca, Gianfranco Peluso, Irene Bonadies, Anna Di Salle and Anna Calarco
Pharmaceutics 2023, 15(3), 805; https://doi.org/10.3390/pharmaceutics15030805 - 1 Mar 2023
Cited by 13 | Viewed by 2847
Abstract
Diabetic wound infections (DWI) represent one of the most costly and disruptive complications in diabetic mellitus. The hyperglycemic state induces a persistent inflammation with immunological and biochemical impairments that promotes delayed wound healing processes and wound infection that often results in extended hospitalization [...] Read more.
Diabetic wound infections (DWI) represent one of the most costly and disruptive complications in diabetic mellitus. The hyperglycemic state induces a persistent inflammation with immunological and biochemical impairments that promotes delayed wound healing processes and wound infection that often results in extended hospitalization and limb amputations. Currently, the available therapeutic options for the management of DWI are excruciating and expensive. Hence, it is essential to develop and improve DWI-specific therapies able to intervene on multiple fronts. Quercetin (QUE) exhibits excellent anti-inflammatory, antioxidant, antimicrobial and wound healing properties, which makes it a promising molecule for the management of diabetic wounds. In the present study, Poly-lactic acid/poly(vinylpyrrolidone) (PP) co-electrospun fibers loaded with QUE were developed. The results demonstrated a bimodal diameter distribution with contact angle starting from 120°/127° and go to 0° in less than 5 s indicating the hydrophilic nature of fabricated samples. The release QUE kinetics, analyzed in simulated wound fluid (SWF), revealed a strong initial burst release, followed by a constant and continuous QUE release. Moreover, QUE-loaded membranes present excellent antibiofilm and anti-inflammatory capacity and significantly reduce the gene expression of M1 markers tumor necrosis factor (TNF)-α, and IL-1β in differentiated macrophages. In conclusion, the results suggested that the prepared mats loaded with QUE could be a hopeful drug-delivery system for the effective treatment of diabetic wound infections. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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Review

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29 pages, 3186 KiB  
Review
Meeting Contemporary Challenges: Development of Nanomaterials for Veterinary Medicine
by Oleksii Danchuk, Anna Levchenko, Rochelly da Silva Mesquita, Vyacheslav Danchuk, Seyda Cengiz, Mehmet Cengiz and Andriy Grafov
Pharmaceutics 2023, 15(9), 2326; https://doi.org/10.3390/pharmaceutics15092326 - 15 Sep 2023
Cited by 3 | Viewed by 4533
Abstract
In recent decades, nanotechnology has been rapidly advancing in various fields of human activity, including veterinary medicine. The review presents up-to-date information on recent advancements in nanotechnology in the field and an overview of the types of nanoparticles used in veterinary medicine and [...] Read more.
In recent decades, nanotechnology has been rapidly advancing in various fields of human activity, including veterinary medicine. The review presents up-to-date information on recent advancements in nanotechnology in the field and an overview of the types of nanoparticles used in veterinary medicine and animal husbandry, their characteristics, and their areas of application. Currently, a wide range of nanomaterials has been implemented into veterinary practice, including pharmaceuticals, diagnostic devices, feed additives, and vaccines. The application of nanoformulations gave rise to innovative strategies in the treatment of animal diseases. For example, antibiotics delivered on nanoplatforms demonstrated higher efficacy and lower toxicity and dosage requirements when compared to conventional pharmaceuticals, providing a possibility to solve antibiotic resistance issues. Nanoparticle-based drugs showed promising results in the treatment of animal parasitoses and neoplastic diseases. However, the latter area is currently more developed in human medicine. Owing to the size compatibility, nanomaterials have been applied as gene delivery vectors in veterinary gene therapy. Veterinary medicine is at the forefront of the development of innovative nanovaccines inducing both humoral and cellular immune responses. The paper provides a brief overview of current topics in nanomaterial safety, potential risks associated with the use of nanomaterials, and relevant regulatory aspects. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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25 pages, 3178 KiB  
Review
Recent Advances in Polymeric Drug Delivery Systems for Peripheral Nerve Regeneration
by Marta Bianchini, Silvestro Micera and Eugenio Redolfi Riva
Pharmaceutics 2023, 15(2), 640; https://doi.org/10.3390/pharmaceutics15020640 - 14 Feb 2023
Cited by 14 | Viewed by 2853
Abstract
When a traumatic event causes complete denervation, muscle functional recovery is highly compromised. A possible solution to this issue is the implantation of a biodegradable polymeric tubular scaffold, providing a biomimetic environment to support the nerve regeneration process. However, in the case of [...] Read more.
When a traumatic event causes complete denervation, muscle functional recovery is highly compromised. A possible solution to this issue is the implantation of a biodegradable polymeric tubular scaffold, providing a biomimetic environment to support the nerve regeneration process. However, in the case of consistent peripheral nerve damage, the regeneration capabilities are poor. Hence, a crucial challenge in this field is the development of biodegradable micro- nanostructured polymeric carriers for controlled and sustained release of molecules to enhance nerve regeneration. The aim of these systems is to favor the cellular processes that support nerve regeneration to increase the functional recovery outcome. Drug delivery systems (DDSs) are interesting solutions in the nerve regeneration framework, due to the possibility of specifically targeting the active principle within the site of interest, maximizing its therapeutical efficacy. The scope of this review is to highlight the recent advances regarding the study of biodegradable polymeric DDS for nerve regeneration and to discuss their potential to enhance regenerative performance in those clinical scenarios characterized by severe nerve damage. Full article
(This article belongs to the Special Issue Biodegradable Nanomaterials for Targeted Drug Delivery)
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