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Pharmaceutics
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Innovative Polymeric Nanocarriers and Their Drug Delivery Applications
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Innovative Polymeric Nanocarriers and Their Drug Delivery Applications

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

Deadline for manuscript submissions: closed (20 December 2022) | Viewed by 17375

Special Issue Editor

Dr. Leonid Gurevich

E-Mail Website
Guest Editor
Department of Materials and Production, Faculty of Engineering and Science, Aalborg University, 9220 Aalborg Ø, Denmark
Interests: nanotechnology; self-assembly; DNA; AFM; drug delivery
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This Special Issue aims to summarize the achievements and highlight the current developments in advanced drug delivery systems based on polymeric nanocarriers. Introduced in the 90s, polymeric nanocarriers have received growing attention during the last ten years with almost ten-fold increase in the number of publications. By far the most common type of polymeric nanocarriers is based on micelles of amphiphilic block copolymers containing hydrophobic and hydrophilic blocks. Compared to surfactant micelles, block copolymer micelles offer multiple advantages, including narrow size distribution and significantly lower critical aggregation concentrations, leading to higher stability and better retention of the drug. Such micelles can be used as both drug and gene delivery systems and offer infinite functionalization capabilities in terms of targeting specific tissues and cells, improving cell uptake and penetration across blood-brain barrier, achieving triggered release, etc. Many other interesting types of polymeric nanocarriers have been demonstrated recently, including DNA origami, polymer-coated nanoparticles, nanogel particles, and electrospan nanomaterials, to name a few.

We welcome your contributions on all aspects of polymeric nanocarriers in this Special Issue.

Dr. Leonid Gurevich
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Pharmaceutics is an international peer-reviewed open access monthly 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 2900 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

  • polymeric nanocarriers
  • drug delivery
  • nanomedicine
  • block copolymers
  • drug and gene delivery

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Published Papers (5 papers)

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Research

25 pages, 5494 KiB  
Article
A β–Sitosterol Encapsulated Biocompatible Alginate/Chitosan Polymer Nanocomposite for the Treatment of Breast Cancer
by Obaid Afzal, Md Habban Akhter, Irfan Ahmad, Khursheed Muzammil, Adam Dawria, Mohammad Zeyaullah, Abdulmalik S. A. Altamimi, Habibullah Khalilullah, Shehla Nasar Mir Najib Ullah, Mohammad Akhlaquer Rahman, Abuzer Ali, Naiyer Shahzad, Mariusz Jaremko, Abdul-Hamid Emwas and Ibrahim Abdel Aziz Ibrahim
Pharmaceutics 2022, 14(8), 1711; https://doi.org/10.3390/pharmaceutics14081711 - 16 Aug 2022
Cited by 21 | Viewed by 3425
Abstract
β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β–sitosterol including lowering low-density lipoprotein [...] Read more.
β–sitosterol is the most abundant type of phytosterol or plant sterol and can be found in various plant dietary sources including natural oils, soy products, and nuts. Numerous studies have demonstrated the potential therapeutic and clinical applications of β–sitosterol including lowering low-density lipoprotein and cholesterol levels, scavenging free radicals in the body, and interestingly, treating and preventing cancer. This study focuses on synthesizing and characterizing β–sitosterol encapsulated Alginate/Chitosan nanoparticles (β–sito–Alg/Ch/NPs) and evaluating their effectiveness in breast cancer treatment and their pharmacokinetic profile in vivo. The synthesized NPs, which incurred a mean size of 25 ± 1 nm, were extensively characterized in vitro for various parameters including surface charge and morphology. The NPs were further analyzed using DSC, FT-IR, thermogravimetry and X-ray diffraction studies. The release of β–sito from NPs was carried out in a bio-relevant medium of pH 7.4 and pH 5.5 and samples were drawn off and analyzed under time frames of 0, 8, 16, 32, 64, 48, 80, and 96 h, and the best kinetic release model was developed after fitting drug release data into different kinetic models. The metabolic activity of MCF-7 cells treated with the prepared formulation was assessed. The radical scavenging potential of β–sito–Alg/Ch/NPs was also studied. The pharmacokinetic parameters including Cmax, Tmax, half-life (t1/2), and bioavailability were measured for β–sito–Alg/Ch/NPs as compared to β–sito–suspension. The β–sito–Alg/Ch/NPs stability was assessed at biological pH 7.4. The % drug release in PBS of pH 7.4 reportedly has shown 41 ± 6% vs. 11 ± 1% from β–sito–Alg/Ch/NPs and β–sito–suspension. In acidic pH 5.5 mimicking the tumor microenvironment has shown 75 ± 9% vs. 12 ± 4% drug release from β–sito–Alg/Ch/NPs and β–sito–suspension. When compared to the β–sito–suspension, the β–sito–Alg/Ch/NPs demonstrated greater cytotoxicity (p < 0.05) and ~3.41-fold higher oral bioavailability. Interestingly, this work demonstrated that β–sito–Alg/Ch/NPs showed higher cytotoxicity due to improved bioavailability and antioxidant potential compared to the β–sito–suspension. Full article
(This article belongs to the Special Issue Innovative Polymeric Nanocarriers and Their Drug Delivery Applications)
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19 pages, 4768 KiB  
Article
Electrospun Poly(lactide) Fibers as Carriers for Controlled Release of Biochanin A
by Ivana Gajić, Sanja Stojanović, Ivan Ristić, Snežana Ilić-Stojanović, Branka Pilić, Aleksandra Nešić, Stevo Najman, Ana Dinić, Ljiljana Stanojević, Maja Urošević, Vesna Nikolić and Ljubiša Nikolić
Pharmaceutics 2022, 14(3), 528; https://doi.org/10.3390/pharmaceutics14030528 - 27 Feb 2022
Cited by 4 | Viewed by 2654
Abstract
The aim of this study is to investigate the possibility of using electrospun polylactide (PLA) fibers as a carrier of the phytoestrogen biochanin A. Polylactide fibers were prepared with different contents of biochanin A by using an electrospinning method at specific process parameters. [...] Read more.
The aim of this study is to investigate the possibility of using electrospun polylactide (PLA) fibers as a carrier of the phytoestrogen biochanin A. Polylactide fibers were prepared with different contents of biochanin A by using an electrospinning method at specific process parameters. The obtained electrospun polylactide fibers, as carriers of biochanin A, were characterized by means of different methods. The presented results showed that the mechanical properties of PLA have not changed significantly in the presence of biochanin A. Scanning electron microscopy showed that the fine fiber structure is retained without visible deformations and biochanin A crystals on the surface of the fibres. The analysis by infrared spectroscopy showed that there are no strong interactions between polylactide and biochanin A molecules, which is a good prerequisite for the diffusion release of biochanin A from PLA fibers.The release of biochanin A from PLA fibers in buffer solution pH 7.4 at 37 °C was monitored by applying the HPLC method. The rate and time of the release of biochanin A from PLA fibers is in correlation with the amount of the active ingredient in the matrix of the carrier and follows zero-order kinetics. PLA fibers with biochanin A exhibit concentration-dependent activity on proliferation and migration of L929 fibroblasts in direct culture system in vitro, and proved to be suitable for a potential formulation for use in wound healing. Full article
(This article belongs to the Special Issue Innovative Polymeric Nanocarriers and Their Drug Delivery Applications)
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24 pages, 7651 KiB  
Article
A Nanosized Codelivery System Based on Intracellular Stimuli-Triggered Dual-Drug Release for Multilevel Chemotherapy Amplification in Drug-Resistant Breast Cancer
by Yufan Guo, Shuo Liu, Fazhen Luo, Dongyun Tang, Tianshu Yang, Xiuru Yang and Yan Xie
Pharmaceutics 2022, 14(2), 422; https://doi.org/10.3390/pharmaceutics14020422 - 15 Feb 2022
Cited by 17 | Viewed by 3439
Abstract
Lacking nano-systems for precisely codelivering the chemotherapeutics paclitaxel (PTX) and the natural P-glycoprotein (P-gp) inhibitor, quercetin (QU), into cancer cells and controlling their intracellular release extremely decreased the anticancer effects in multidrug resistant (MDR) tumors. To overcome this hurdle, we constructed hybrid polymeric [...] Read more.
Lacking nano-systems for precisely codelivering the chemotherapeutics paclitaxel (PTX) and the natural P-glycoprotein (P-gp) inhibitor, quercetin (QU), into cancer cells and controlling their intracellular release extremely decreased the anticancer effects in multidrug resistant (MDR) tumors. To overcome this hurdle, we constructed hybrid polymeric nanoparticles (PNPs) which consist of redox-sensitive PTX/polyethyleneimine-tocopherol hydrogen succinate-dithioglycollic acid PNPs and pH-sensitive hyaluronic acid-QU conjugates. The obtained hybrid PNPs can be internalized into drug-resistant breast cancer cells by the hyaluronic acid/CD44-mediated endocytosis pathway and escape from the lysosome through the “proton sponge effect”. Under the trigger of intracellular stimuli, the nanoplatform used the pH/glutathione dual-sensitive disassembly to release QU and PTX. The PTX diffused into microtubules to induce tumor cell apoptosis, while QU promoted PTX retention by down-regulating P-gp expression. Moreover, tocopherol hydrogen succinate and QU disturbed mitochondrial functions by generating excessive reactive oxygen species, decreasing the mitochondrial membrane potential, and releasing cytochrome c into the cytosol which consequently achieved intracellular multilevel chemotherapy amplification in MDR cancers. Importantly, the PNPs substantially suppressed tumors growth with an average volume 2.54-fold lower than that of the control group in the MCF-7/ADR tumor-bearing nude mice model. These presented PNPs would provide a valuable reference for the coadministration of natural compounds and anticarcinogens for satisfactory combination therapy in MDR cancers. Full article
(This article belongs to the Special Issue Innovative Polymeric Nanocarriers and Their Drug Delivery Applications)
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16 pages, 2981 KiB  
Article
Amphiphilic Poly(N-vinylpyrrolidone) Nanoparticles Conjugated with DR5-Specific Antitumor Cytokine DR5-B for Targeted Delivery to Cancer Cells
by Anne Yagolovich, Andrey Kuskov, Pavel Kulikov, Leily Kurbanova, Dmitry Bagrov, Artem Artykov, Marine Gasparian, Svetlana Sizova, Vladimir Oleinikov, Anastasia Gileva, Mikhail Kirpichnikov, Dmitry Dolgikh and Elena Markvicheva
Pharmaceutics 2021, 13(9), 1413; https://doi.org/10.3390/pharmaceutics13091413 - 7 Sep 2021
Cited by 11 | Viewed by 3200
Abstract
Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions. As is well known, [...] Read more.
Nanoparticles based on the biocompatible amphiphilic poly(N-vinylpyrrolidone) (Amph-PVP) derivatives are promising for drug delivery. Amph-PVPs self-aggregate in aqueous solutions with the formation of micellar nanoscaled structures. Amph-PVP nanoparticles are able to immobilize therapeutic molecules under mild conditions. As is well known, many efforts have been made to exploit the DR5-dependent apoptosis induction for cancer treatment. The aim of the study was to fabricate Amph-PVP-based nanoparticles covalently conjugated with antitumor DR5-specific TRAIL (Tumor necrosis factor-related apoptosis-inducing ligand) variant DR5-B and to evaluate their in vitro cytotoxicity in 3D tumor spheroids. The Amph-PVP nanoparticles were obtained from a 1:1 mixture of unmodified and maleimide-modified polymeric chains, while DR5-B protein was modified by cysteine residue at the N-end for covalent conjugation with Amph-PVP. The nanoparticles were found to enhance cytotoxicity effects compared to those of free DR5-B in both 2D (monolayer culture) and 3D (tumor spheroids) in vitro models. The cytotoxicity of the nanoparticles was investigated in human cell lines, namely breast adenocarcinoma MCF-7 and colorectal carcinomas HCT116 and HT29. Notably, DR5-B conjugation with Amph-PVP nanoparticles sensitized resistant multicellular tumor spheroids from MCF-7 and HT29 cells. Taking into account the nanoparticles loading ability with a wide range of low-molecular-weight antitumor chemotherapeutics into hydrophobic core and feasibility of conjugation with hydrophilic therapeutic molecules by click chemistry, we suggest further development to obtain a versatile system for targeted drug delivery into tumor cells. Full article
(This article belongs to the Special Issue Innovative Polymeric Nanocarriers and Their Drug Delivery Applications)
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16 pages, 3098 KiB  
Article
Bio- and Hemo-Compatible Silk Fibroin PEGylated Nanocarriers for 5-Fluorouracil Chemotherapy in Colorectal Cancer: In Vitro Studies
by Ariana Hudiță, Ionuț Cristian Radu, Cătălin Zaharia, Andreea Cristina Ion, Octav Ginghină, Bianca Gălățeanu, Luminița Măruțescu, Florin Grama, Aristidis Tsatsakis, Leonid Gurevich and Marieta Costache
Pharmaceutics 2021, 13(5), 755; https://doi.org/10.3390/pharmaceutics13050755 - 19 May 2021
Cited by 11 | Viewed by 3361
Abstract
5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to [...] Read more.
5-fluorouracil (5-FU) remains the gold standard of treatment for colorectal cancer, but its poor bioavailability and high systemic toxicity highlight the urgent need for the development of novel delivery strategies to increase the efficacy of 5-FU treatment. The present study is aimed to design and validate a PEGylated Silk Fibroin Nanocarrier (SF/PEG nanoparticles (NPs)) as an efficient 5-FU delivery system for potential intravenous administration. Using the human adenocarcinoma HT–29 cell line as an in vitro model for colorectal cancer, the cytotoxicity screening of the SF/PEG NPs showed that pristine nanocarriers were highly biocompatible, while the addition of 5-FU triggers a dramatic reduction in tumor cell viability, proliferation potential and mitochondrial integrity as well as a significant increase in nitric oxide production. Despite their high in vitro cytotoxicity, the 5-FU SF/PEG NPs were found hemocompatible as no impact on red blood cells hemolysis or the phagocytic activity of the granulocytes was observed. Exposure of HT–29 tumor cells and blood samples to 5-FU SF/PEG NPs augmented the tumor necrosis factor-α levels. Moreover, 5-FU SF/PEG NPs showed an impact on tumor cell migration and invasive potential as both of these processes were inhibited by the NP treatment. Full article
(This article belongs to the Special Issue Innovative Polymeric Nanocarriers and Their Drug Delivery Applications)
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