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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 March 2023) | Viewed by 11626

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Special Issue Editor

Dr. Lacey R. McNally

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Guest Editor

Department of Surgery, University of Oklahoma, Oklahoma City, OK 73104, USA
Interests: nano-contrast agents; nano-drug delivery; pancreatic cancer; ovarian cancer; breast cancer

Special Issue Information

Dear Colleagues,

Nanoparticles may significantly impact the development of therapeutic and diagnostic agents that target various diseases. While many nanoparticle formulations are newly developed or remain in the pre-clinical testing stage, a few nanoformulations have demonstrated clinical relevance through their capacity to increase drug efficacy and disease-specific accumulation, decrease drug toxicity, and improve contrast for disease-specific diagnosis or monitoring. Nanoparticles are well-suited to the role of drug-delivery vehicles or contrast agents due to their potential for surface functionalization or modification and active targeting moieties, capacity for stimuli-responsive delivery drugs or contrast agents, and generally longer circulation times.

The Special Issue will cover recent advancements in nanoparticle design, drug-delivery, and imaging applications, characterization, toxicity, and the potential role of nanoparticles as disease-specific or multi-modal contrast agents.

You are invited to contribute to this Special Issue of Pharmaceutics, entitled “Nanoparticles for Imaging and Drug Delivery”, which will focus on the utility of nanoparticles as drug-delivery agents, imaging contrast agents, and determination of nanoparticle features required for their translation into clinical settings.

Dr. Lacey R. McNally
Guest Editor

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Keywords

nano drug delivery
nanocontrast agents
nanotheranostics
nanoparticle toxicity
targeted nanoparticles
nano imaging agents

Published Papers (6 papers)

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Research

17 pages, 3506 KiB

Open AccessEditor’s ChoiceArticle

Iron Oxide Nanoparticle-Mediated mRNA Delivery to Hard-to-Transfect Cancer Cells

by Jianxi Huang, Guanyou Lin, Taylor Juenke, Seokhwan Chung, Nicholas Lai, Tianxin Zhang, Tianyi Zhang and Miqin Zhang

Pharmaceutics 2023, 15(7), 1946; https://doi.org/10.3390/pharmaceutics15071946 - 14 Jul 2023

Viewed by 1444

Abstract

mRNA-based therapeutics have emerged as a promising strategy for cancer treatment. However, the effective delivery of mRNA into hard-to-transfect cancer cells remains a significant challenge. This study introduces a novel approach that utilizes iron oxide nanoparticles (NPs) synthesized through a layer-by-layer (LbL) method for safe and efficient mRNA delivery. The developed NPs consist of an iron oxide core modified with a thin charge-bearing layer, an mRNA middle layer, and an outer layer composed of perfluorinated polyethyleneimine with heparin (PPH), which facilitates efficient mRNA delivery. Through a comparative analysis of four nanoparticle delivery formulations, we investigated the effects of the iron oxide core’s surface chemistry and surface charge on mRNA complexation, cellular uptake, and mRNA release. We identified an optimal and effective mRNA delivery platform, namely, (IOCCP)-mRNA-PPH, capable of transporting mRNA into various hard-to-transfect cancer cell lines in vitro. The (IOCCP)-mRNA-PPH formulation demonstrated significant enhancements in cellular internalization of mRNA, facilitated endosomal escape, enabled easy mRNA release, and exhibited minimal cytotoxicity. These findings suggest that (IOCCP)-mRNA-PPH holds great promise as a solution for mRNA therapy against hard-to-transfect cancers. Full article

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

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15 pages, 2840 KiB

Open AccessArticle

Encapsulation of PI3K Inhibitor LY294002 within Polymer Nanoparticles Using Ion Pairing Flash Nanoprecipitation

by Austin D. Fergusson, Rui Zhang, Judy S. Riffle and Richey M. Davis

Pharmaceutics 2023, 15(4), 1157; https://doi.org/10.3390/pharmaceutics15041157 - 6 Apr 2023

Cited by 3 | Viewed by 1437

Abstract

Flash nanoprecipitation (FNP) is a turbulent mixing process capable of reproducibly producing polymer nanoparticles loaded with active pharmaceutical ingredients (APIs). The nanoparticles produced with this method consist of a hydrophobic core surrounded by a hydrophilic corona. FNP produces nanoparticles with very high loading levels of nonionic hydrophobic APIs. However, hydrophobic compounds with ionizable groups are not as efficiently incorporated. To overcome this, ion pairing agents (IPs) can be incorporated into the FNP formulation to produce highly hydrophobic drug salts that efficiently precipitate during mixing. We demonstrate the encapsulation of the PI3K inhibitor, LY294002, within poly(ethylene glycol)-b-poly(D,L lactic acid) nanoparticles. We investigated how incorporating two hydrophobic IPs (palmitic acid (PA) and hexadecylphosphonic acid (HDPA)) during the FNP process affected the LY294002 loading and size of the resulting nanoparticles. The effect of organic solvent choice on the synthesis process was also examined. While the presence of either hydrophobic IP effectively increased the encapsulation of LY294002 during FNP, HDPA resulted in well-defined colloidally stable particles, while the PA resulted in ill-defined aggregates. The incorporation of hydrophobic IPs with FNP opens the door for the intravenous administration of APIs that were previously deemed unusable due to their hydrophobic nature. Full article

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

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16 pages, 6134 KiB

Open AccessArticle

Polydopamine-Coated Cu-BTC Nanowires for Effective Magnetic Resonance Imaging and Photothermal Therapy

by Senthilkumar Thirumurugan, Kayalvizhi Samuvel Muthiah, Rajalakshmi Sakthivel, Mei-Yi Liao, Hitoshi Kasai and Ren-Jei Chung

Pharmaceutics 2023, 15(3), 822; https://doi.org/10.3390/pharmaceutics15030822 - 2 Mar 2023

Cited by 7 | Viewed by 1628

Abstract

Herein, we present a one-pot hydrothermal approach for synthesizing metal–organic framework-derived copper (II) benzene-1,3,5-tricarboxylate (Cu-BTC) nanowires (NWs) using dopamine as the reducing agent and precursor for a polydopamine (PDA) surface coating formation. In addition, PDA can act as a PTT agent and enhance NIR absorption, producing photothermal effects on cancer cells. These NWs displayed a photothermal conversion efficiency of 13.32% after PDA coating and exhibited good photothermal stability. Moreover, NWs with a suitable T₁ relaxivity coefficient (r₁ = 3.01 mg⁻¹ s⁻¹) can be effectively used as magnetic resonance imaging (MRI) contrast agents. By increasing concentrations, cellular uptake studies showed a greater uptake of Cu-BTC@PDA NWs into cancer cells. Further, in vitro studies showed PDA-coated Cu-BTC NWs possess exceptional therapeutic performance by 808 nm laser irradiation, destroying 58% of cancer cells compared with the absence of laser irradiation. This promising performance is anticipated to advance the research and implementation of copper-based NWs as theranostic agents for cancer treatment. Full article

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

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17 pages, 7048 KiB

Open AccessArticle

Green Synthesis of Blue-Emitting Graphene Oxide Quantum Dots for In Vitro CT26 and In Vivo Zebrafish Nano-Imaging as Diagnostic Probes

by Govinda Gorle, Ganesh Gollavelli, Gowreeswari Nelli and Yong-Chien Ling

Pharmaceutics 2023, 15(2), 632; https://doi.org/10.3390/pharmaceutics15020632 - 13 Feb 2023

Cited by 6 | Viewed by 2130

Abstract

Graphene oxide quantum dots (GOQDs) are prepared using black carbon as a feedstock and H₂O₂ as a green oxidizing agent in a straightforward and environmentally friendly manner. The process adopted microwave energy and only took two minutes. The GOQDs are 20 nm in size and have stable blue fluorescence at 440 nm. The chemical characteristics and QD morphology were confirmed by thorough analysis using scanning electron microscope (SEM), transmission electron microscope (TEM), atomic force microscope (AFM), Fourier transmission infra-red (FT-IR), and X-ray photoelectron spectroscopy (XPS). The biocompatibility test was used to evaluate the toxicity of GOQDs in CT26 cells in vitro and the IC₅₀ was found to be 200 µg/mL with excellent survival rates. Additional in vivo toxicity assessment in the developing zebrafish (Danio rerio) embryo model found no observed abnormalities even at a high concentration of 400 μg/mL after 96 h post fertilization. The GOQDs luminescence was also tested both in vitro and in vivo. They showed excellent internal distribution in the cytoplasm, cell nucleus, and throughout the zebrafish body. As a result, the prepared GOQDs are expected to be simple and inexpensive materials for nano-imaging and diagnostic probes in nanomedicine. Full article

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

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18 pages, 3859 KiB

Open AccessArticle

Rare-Earth-Metal (Nd³⁺, Ce³⁺ and Gd³⁺)-Doped CaF₂: Nanoparticles for Multimodal Imaging in Biomedical Applications

by Zhenfeng Yu, Yuanyuan He, Timo Schomann, Kefan Wu, Yang Hao, Ernst Suidgeest, Hong Zhang, Christina Eich and Luis J. Cruz

Pharmaceutics 2022, 14(12), 2796; https://doi.org/10.3390/pharmaceutics14122796 - 14 Dec 2022

Cited by 4 | Viewed by 1812 | Correction

Abstract

Here, we describe the synthesis of a novel type of rare-earth-doped nanoparticles (NPs) for multimodal imaging, by combining the rare-earth elements Ce, Gd and Nd in a crystalline host lattice consisting of CaF₂ (CaF₂: Ce, Gd, Nd). CaF₂: Ce, Gd, Nd NPs are small (15–20 nm), of uniform shape and size distribution, and show good biocompatibility and low immunogenicity in vitro. In addition, CaF₂: Ce, Gd, Nd NPs possess excellent optical properties. CaF₂: Ce, Gd, Nd NPs produce downconversion emissions in the second near-infrared window (NIR-II, 1000–1700 nm) under 808 nm excitation, with a strong emission peak at 1056 nm. Excitation in the first near- infrared window (NIR-I, 700–900 nm) has the advantage of deeper tissue penetration power and reduced autofluorescence, compared to visible light. Thus, CaF₂: Ce, Gd, Nd NPs are ideally suited for in vivo fluorescence imaging. In addition, the presence of Gd³⁺ makes the NPs intrinsically monitorable by magnetic resonance imaging (MRI). Moreover, next to fluorescence and MR imaging, our results show that CaF₂: Ce, Gd, Nd NPs can be used as imaging probes for photoacoustic imaging (PAI) in vitro. Therefore, due to their biocompatibility and suitability as multimodal imaging probes, CaF₂: Ce, Gd, Nd NPs exhibit great potential as a traceable imaging agent in biomedical applications. Full article

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

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16 pages, 6101 KiB

Open AccessArticle

Toxicity Assessment of Mesoporous Silica Nanoparticles upon Intravenous Injection in Mice: Implications for Drug Delivery

by William M. MacCuaig, Abhilash Samykutty, Jeremy Foote, Wenyi Luo, Alexander Filatenkov, Min Li, Courtney Houchen, William E. Grizzle and Lacey R. McNally

Pharmaceutics 2022, 14(5), 969; https://doi.org/10.3390/pharmaceutics14050969 - 30 Apr 2022

Cited by 9 | Viewed by 2402

Abstract

Nanoparticles are popular tools utilized to selectively deliver drugs and contrast agents for identification and treatment of disease. To determine the usefulness and translational potential of mesoporous silica nanoparticles (MSNs), further evaluations of toxicity are required. MSNs are among the most utilized nano-delivery systems due to ease of synthesis, pore structure, and functionalization. This study aims to elucidate toxicity as a result of intravenous injection of 25 nm MSNs coated with chitosan (C) or polyethylene glycol (PEG) in mice. Following acute and chronic injections, blood was evaluated for standard blood chemistry and complete blood count analyses. Blood chemistry results primarily indicated that no abnormalities were present following acute or chronic injections of MSNs, or C/PEG-coated MSNs. After four weekly administered treatments, vital organs showed minor exacerbation of pre-existing lesions in the 35KPEG-MSN and moderate exacerbation of pre-existing lesions in uncoated MSN and 2KPEG-MSN treatment groups. In contrast, C-MSN treatment groups had minimal changes compared to controls. This study suggests 25 nm MSNs coated with chitosan should elicit minimal toxicity when administered as either single or multiple intravenous injections, but MSNs coated with PEG, especially 2KPEG may exacerbate pre-existing vascular conditions. Further studies should evaluate varying sizes and types of nanoparticles to provide a better overall understanding on the relation between nanoparticles and in vivo toxicity. Full article

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

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