Submit to Pharmaceutics Review for Pharmaceutics Propose a Special Issue

Journal Browser

Nanogels and Nanoparticles for Selective Drug Delivery

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (25 February 2023) | Viewed by 22214

Share This Special Issue

Special Issue Editors

Prof. Dr. Slawomir Kadlubowski

E-Mail Website
Guest Editor

Institute of Applied Radiation Chemistry, Lodz University of Technology, Wroblewskiego 15, 93-590 Lodz, Poland
Interests: Ionizing radiation; nanogel; biomaterial; nanotechnology
Special Issues, Collections and Topics in MDPI journals

Dr. Gustavo H. C. Varca

E-Mail Website
Guest Editor

E-BEAM Services, Inc., 118 Melrich Road, Cranbury, NJ, USA
Interests: ionizing radiation; nanoparticle; biomaterial, nanotechnology

Special Issue Information

Dear Colleagues,

Nanotechnology triggered the development of materials with advanced applications over the last several decades, and such materials are currently replacing old ones in our daily lives at a considerable pace. Specific applications of nanotechnology for the treatment, diagnosis, monitoring, and control of biological systems have recently been referred to as “nanomedicine”. Research into the rational delivery and targeting of pharmaceutical, therapeutic, and diagnostic agents is at the forefront of projects in this field. These involve the identification of precise targets (cells and receptors) related to specific clinical conditions and the choice of the appropriate nanocarriers to achieve the required responses while minimizing the side effects. Some of the most promising types of transport molecules are nanogels and nanoparticles.

Authors are invited to submit original and review articles describing basic science, preclinical, and clinical findings that contribute to our understanding of the current and future potential applications of nanogels and nanoparticles (organic, metal, and inorganic) for selective drug delivery, to be published in this Special Issue of Pharmaceutics.

Prof. Dr. Slawomir Kadlubowski
Dr. Gustavo H. C. Varca
Guest Editors

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

nanogel
nanoparticle
drug delivery
synthesis
clinical trials
nanotechnology
nanomedicine
in vitro and in vivo testing

Published Papers (9 papers)

Download All Papers

Research

Jump to: Review

19 pages, 14492 KiB

Open AccessArticle

Two-Step Preparation of Protein-Decorated Biohybrid Quantum Dot Nanoparticles for Cellular Uptake

by Agata Noelia Traverso, David José Fragale, Diego Luis Viale, Octavio Garate, Pablo Torres, Gastón Valverde, Alejandro Berra, Ana Vanesa Torbidoni, Juan Sebastián Yakisich, Mariano Grasselli and Martín Radrizzani

Pharmaceutics 2023, 15(6), 1651; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15061651 - 03 Jun 2023

Viewed by 1630

Abstract

Decoration of nanoparticles with specific molecules such as antibodies, peptides, and proteins that preserve their biological properties is essential for the recognition and internalization of their specific target cells. Inefficient preparation of such decorated nanoparticles leads to nonspecific interactions diverting them from their desired target. We report a simple two-step procedure for the preparation of biohybrid nanoparticles containing a core of hydrophobic quantum dots coated with a multilayer of human serum albumin. These nanoparticles were prepared by ultra-sonication, crosslinked using glutaraldehyde, and decorated with proteins such as human serum albumin or human transferrin in their native conformations. These nanoparticles were homogeneous in size (20–30 nm), retained the fluorescent properties of quantum dots, and did not show a “corona effect” in the presence of serum. The uptake of transferrin-decorated quantum dot nanoparticles was observed in A549 lung cancer and SH-SY5Y neuroblastoma cells but not in non-cancerous 16HB14o- or retinoic acid dopaminergic neurons differentiated SH-SY5Y cells. Furthermore, digitoxin-loaded transferrin-decorated nanoparticles decreased the number of A549 cells without effect on 16HB14o-. Finally, we analyzed the in vivo uptake of these biohybrids by murine retinal cells, demonstrating their capacity to selectively target and deliver into specific cell types with excellent traceability. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Graphical abstract

24 pages, 5841 KiB

Open AccessArticle

Influence of Ionizing Radiation on Spontaneously Formed Aggregates in Proteins or Enzymes Solutions

by Karolina Radomska and Marian Wolszczak

Pharmaceutics 2023, 15(5), 1367; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15051367 - 29 Apr 2023

Viewed by 1143

Abstract

We have shown that many proteins and enzymes (ovalbumin, β-lactoglobulin, lysozyme, insulin, histone, papain) undergo concentration-dependent reversible aggregation as a result of the interaction of the studied biomolecules. Moreover, irradiation of those protein or enzyme solutions under oxidative stress conditions results in the formation of stable soluble protein aggregates. We assume that protein dimers are mainly formed. A pulse radiolysis study has been made to investigate the early stages of protein oxidation by

N_{3}^{•}

or ^•OH radicals. Reactions of the

N_{3}^{•}

radical with the studied proteins lead to the generation of aggregates stabilized by covalent bonds between tyrosine residues. The high reactivity of the ^•OH with amino acids contained within proteins is responsible for the formation of various covalent bonds (including C–C or C–O–C) between adjacent protein molecules. In the analysis of the formation of protein aggregates, intramolecular electron transfer from the tyrosine moiety to Trp^• radical should be taken into account. Steady-state spectroscopic measurements with a detection of emission and absorbance, together with measurements of the dynamic scattering of laser light, made it possible to characterize the obtained aggregates. The identification of protein nanostructures generated by ionizing radiation using spectroscopic methods is difficult due to the spontaneous formation of protein aggregates before irradiation. The commonly used fluorescence detection of dityrosyl cross-linking (DT) as a marker of protein modification under the influence of ionizing radiation requires modification in the case of the tested objects. A precise photochemical lifetime measurement of the excited states of radiation-generated aggregates is useful in characterizing their structure. Resonance light scattering (RLS) has proven to be an extremely sensitive and useful technique to detect protein aggregates. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Figure 1

26 pages, 8198 KiB

Open AccessArticle

pH-Responsive Water-Soluble Chitosan Amphiphilic Core–Shell Nanoparticles: Radiation-Assisted Green Synthesis and Drug-Controlled Release Studies

by Thananchai Piroonpan, Pakjira Rimdusit, Saowaluk Taechutrakul and Wanvimol Pasanphan

Pharmaceutics 2023, 15(3), 847; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15030847 - 05 Mar 2023

Cited by 5 | Viewed by 1474

Abstract

This work aims to apply water radiolysis-mediated green synthesis of amphiphilic core–shell water-soluble chitosan nanoparticles (WCS NPs) via free radical graft copolymerization in an aqueous solution using irradiation. Robust grafting poly(ethylene glycol) monomethacrylate (PEGMA) comb-like brushes were established onto WCS NPs modified with hydrophobic deoxycholic acid (DC) using two aqueous solution systems, i.e., pure water and water/ethanol. The degree of grafting (DG) of the robust grafted poly(PEGMA) segments was varied from 0 to ~250% by varying radiation-absorbed doses from 0 to 30 kGy. Using reactive WCS NPs as a water-soluble polymeric template, a high amount of DC conjugation and a high degree of poly(PEGMA) grafted segments brought about high moieties of hydrophobic DC and a high DG of the poly(PEGMA) hydrophilic functions; meanwhile, the water solubility and NP dispersion were also markedly improved. The DC-WCS-PG building block was excellently self-assembled into the core–shell nanoarchitecture. The DC-WCS-PG NPs efficiently encapsulated water-insoluble anticancer and antifungal drugs, i.e., paclitaxel (PTX) and berberine (BBR) (~360 mg/g). The DC-WCS-PG NPs met the role of controlled release with a pH-responsive function due to WCS compartments, and they showed a steady state for maintaining drugs for up to >10 days. The DC-WCS-PG NPs prolonged the inhibition capacity of BBR against the growth of S. ampelinum for 30 days. In vitro cytotoxicity results of the PTX-loaded DC-WCS-PG NPs with human breast cancer cells and human skin fibroblast cells proved the role of the DC-WCS-PG NPs as a promising nanoplatform for controlling drug release and reducing the side effects of the drugs on normal cells. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Graphical abstract

16 pages, 2660 KiB

Open AccessArticle

Synthesis of Small Peptide Nanogels Using Radiation Crosslinking as a Platform for Nano-Imaging Agents for Pancreatic Cancer Diagnosis

by Atsushi Kimura, Tadashi Arai, Miho Ueno, Kotaro Oyama, Hao Yu, Shinichi Yamashita, Yudai Otome and Mitsumasa Taguchi

Pharmaceutics 2022, 14(11), 2400; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14112400 - 07 Nov 2022

Cited by 3 | Viewed by 1349

Abstract

Nanoparticle-based drug delivery systems (DDS) have been developed as effective diagnostic and low-dose imaging agents. Nano-imaging agents with particles greater than 100 nm are difficult to accumulate in pancreatic cancer cells, making high-intensity imaging of pancreatic cancer challenging. Peptides composed of histidine and glycine were designed and synthesized. Additionally, aqueous peptide solutions were irradiated with γ-rays to produce peptide nanogels with an average size of 25–53 nm. The mechanisms underlying radiation-mediated peptide crosslinking were investigated by simulating peptide particle formation based on rate constants. The rate constants for reactions between peptides and reactive species produced by water radiolysis were measured using pulse radiolysis. HGGGHGGGH (H9, H—histidine; G—glycine) particles exhibited a smaller size, as well as high formation yield, stability, and biodegradability. These particles were labeled with fluorescent dye to change their negative surface potential and enhance their accumulation in pancreatic cancer cells. Fluorescent-labeled H9 particles accumulated in PANC1 human pancreatic cancer cells, demonstrating that these particles are effective nano-imaging agents for intractable cancers. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Graphical abstract

18 pages, 80225 KiB

Open AccessArticle

Clay Nanotube Immobilization on Animal Hair for Sustained Anti-Lice Protection

by Naureen Rahman, Faith Hannah Scott, Yuri Lvov, Anna Stavitskaya, Farida Akhatova, Svetlana Konnova, Gӧlnur Fakhrullina and Rawil Fakhrullin

Pharmaceutics 2021, 13(9), 1477; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091477 - 15 Sep 2021

Cited by 15 | Viewed by 4875

Abstract

Topical administration of drugs is required for the treatment of parasitic diseases and insect infestations; therefore, fabrication of nanoscale drug carriers for effective insecticide topical delivery is needed. Here we report the enhanced immobilization of halloysite tubule nanoclay onto semiaquatic capybaras which have hydrophobic hair surfaces as compared to their close relatives, land-dwelling guinea pigs, and other agricultural livestock. The hair surface of mammals varies in hydrophobicity having a cortex surrounded by cuticles. Spontaneous 1–2 µm thick halloysite hair coverages on the semi-aquatic rodent capybara, non-aquatic rodent guinea pig, and farm goats were compared. The best coating was found for capybara due to the elevated 5 wt% wax content. As a result, we suggest hair pretreatment with diluted wax for enhanced nanoclay adsorption. The formation of a stable goat hair coverage with a 2–3 µm halloysite layer loaded with permethrin insecticide allowed for long-lasting anti-parasitic protection, enduring multiple rain wettings and washings. We expect that our technology will find applications in animal parasitosis protection and may be extended to prolonged human anti-lice treatment. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Graphical abstract

26 pages, 2521 KiB

Open AccessArticle

Synthesis and Properties of Targeted Radioisotope Carriers Based on Poly(Acrylic Acid) Nanogels

by Małgorzata Matusiak, Beata P. Rurarz, Sławomir Kadłubowski, Marian Wolszczak, Urszula Karczmarczyk, Michał Maurin, Beata Kolesińska and Piotr Ulański

Pharmaceutics 2021, 13(8), 1240; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13081240 - 11 Aug 2021

Cited by 9 | Viewed by 2665

Abstract

Radiation crosslinking was employed to obtain nanocarriers based on poly(acrylic acid)—PAA—for targeted delivery of radioactive isotopes. These nanocarriers are internally crosslinked hydrophilic macromolecules—nanogels—bearing carboxylic groups to facilitate functionalization. PAA nanogels were conjugated with an engineered bombesin-derivative—oligopeptide combined with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate chelating moiety, aimed to provide selective radioligand transport. 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium (DMTMM) toluene-4-sulfonate was used as the coupling agent. After tests on a model amine—p-toluidine—both commercial and home-synthesized DOTA-bombesin were successfully coupled to the nanogels and the obtained products were characterized. The radiolabeling efficiency of nanocarriers with ¹⁷⁷Lu, was chromatographically tested. The results provide a proof of concept for the synthesis of radiation-synthesized nanogel-based radioisotope nanocarriers for theranostic applications. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Graphical abstract

12 pages, 2172 KiB

Open AccessCommunication

Semi-Solid Pharmaceutical Formulations for the Delivery of Papain Nanoparticles

by Caroline S. A. de Lima, Justine P. R. O. Varca, Kamila M. Nogueira, Gabriela N. Fazolin, Lucas F. de Freitas, Eliseu W. de Souza, Ademar B. Lugão and Gustavo. H. C. Varca

Pharmaceutics 2020, 12(12), 1170; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics12121170 - 01 Dec 2020

Cited by 2 | Viewed by 2422

Abstract

Papain is a therapeutic enzyme with restricted applications due to associated allergenic reactions. Papain nanoparticles have shown to be safe for biomedical use, although a method for proper drug loading and release remains to be developed. Thus, the objective of this work was to develop and assess the stability of papain nanoparticles in a prototype semi-solid formulation suitable for dermatological or topical administrations. Papain nanoparticles of 7.0 ± 0.1 nm were synthesized and loaded into carboxymethylcellulose- and poly(vinyl alcohol)-based gels. The formulations were then assayed for preliminary stability, enzyme activity, cytotoxicity studies, and characterized according to their microstructures and protein distribution. The formulations were suitable for papain nanoparticle loading and provided a stable environment for the nanoparticles. The enzyme distribution along the gel matrix was homogeneous for all the formulations, and the proteolytic activity was preserved after the gel preparation. Both gels presented a slow release of the papain nanoparticles for four days. Cell viability assays revealed no potential cytotoxicity, and the presence of the nanoparticles did not alter the microstructure of the gel. The developed systems presented a potential for biomedical applications, either as drug delivery systems for papain nanoparticles and/or its complexes. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Figure 1

Review

Jump to: Research

28 pages, 26131 KiB

Open AccessReview

On the Mechanism and Kinetics of Synthesizing Polymer Nanogels by Ionizing Radiation-Induced Intramolecular Crosslinking of Macromolecules

by Aiysha Ashfaq, Jung-Chul An, Piotr Ulański and Mohamad Al-Sheikhly

Pharmaceutics 2021, 13(11), 1765; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13111765 - 22 Oct 2021

Cited by 6 | Viewed by 2026

Abstract

Nanogels—internally crosslinked macromolecules—have a growing palette of potential applications, including as drug, gene or radioisotope nanocarriers and as in vivo signaling molecules in modern diagnostics and therapy. This has triggered considerable interest in developing new methods for their synthesis. The procedure based on intramolecular crosslinking of polymer radicals generated by pulses of ionizing radiation has many advantages. The substrates needed are usually simple biocompatible polymers and water. This eliminates the use of monomers, chemical crosslinking agents, initiators, surfactants, etc., thus limiting potential problems with the biocompatibility of products. This review summarizes the basics of this method, providing background information on relevant aspects of polymer solution thermodynamics, radiolysis of aqueous solutions, generation and reactions of polymer radicals, and the non-trivial kinetics and mechanism of crosslinking, focusing on the main factors influencing the outcomes of the radiation synthesis of nanogels: molecular weight of the starting polymer, its concentration, irradiation mode, absorbed dose of ionizing radiation and temperature. The most important techniques used to perform the synthesis, to study the kinetics and mechanism of the involved reactions, and to assess the physicochemical properties of the formed nanogels are presented. Two select important cases, the synthesis of nanogels based on polyvinylpyrrolidone (PVP) and/or poly(acrylic acid) (PAA), are discussed in more detail. Examples of recent application studies on radiation-synthesized PVP and PAA nanogels in transporting drugs across the blood–brain barrier and as targeted radioisotope carriers in nanoradiotherapy are briefly described. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures

Figure 1

18 pages, 766 KiB

Open AccessReview

Antimicrobial Polymer-Based Hydrogels for the Intravaginal Therapies—Engineering Considerations

by Monika Gosecka and Mateusz Gosecki

Pharmaceutics 2021, 13(9), 1393; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13091393 - 02 Sep 2021

Cited by 15 | Viewed by 3198

Abstract

The review is focused on the hydrogel systems dedicated to the intravaginal delivery of antibacterial, antifungal and anti-Trichomonas vaginalis activity drugs for the treatment of gynaecological infections. The strategies for the enhancement of the hydrophobic drug solubility in the hydrogel matrix based on the formation of bigel systems and the introduction of nano- and microparticles as a drug reservoir are presented. Hydrogel carriers of natural and synthetic pharmacological substances, drug-free systems displaying antimicrobial activity thanks to the hydrogel building elements and systems combining the antimicrobial activity of both drug and polymer building components are distinguished. The design of hydrogels facilitating their administration and proper distribution in the vaginal mucosa and the vagina based on thermoresponsive systems capable of gelling at vaginal conditions and already-cross-linked injectable systems after reaching the yield stress are discussed. In addition, the mechanisms of hydrogel bioadhesion that regulate the retention time in the vagina are indicated. Finally, the prospects for the further development of hydrogel-based drug carriers in gynaecological therapies are highlighted. Full article

(This article belongs to the Special Issue Nanogels and Nanoparticles for Selective Drug Delivery)

► Show Figures