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Pharmaceutics
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Bioactive Materials in Drug-Delivery Systems
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Bioactive Materials in Drug-Delivery Systems

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

Deadline for manuscript submissions: closed (20 September 2022) | Viewed by 15170

Special Issue Editors

Prof. Dr. Ping-Shan Lai

E-Mail Website
Guest Editor
Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan
Interests: biomaterials; drug delivery; nanomedicine; cancer therapy; smart materials
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Martin Hsiu-Chu Lin

E-Mail Website
Guest Editor
Department of Neurosurgery, Chang Gung Memorial Hospital Chia-Yi, Chia-Yi 61363, Taiwan
Interests: cancer nanomedicine; neuroprotection; phototherapy

Special Issue Information

Dear Colleagues,

Research into the pharmacologic applications of nanotechnology-based drug-delivery systems has expanded in the past decade.  With increasing sophistication in design and functionalities, newer target-specific and individualized treatments are now possible.  The selection of either natural or synthetic materials for drug-delivery systems is no longer just a passive delivery vehicle, but displays biophysicochemical dimensions that interact with the biologic microenvironment. These include the optimization of circulation kinetics and tissue distribution, targeted drug delivery, environment-responsive controlled-release, and anti-inflammatory or immunomodulatory properties.

The scope of this Special Issue is to gather the latest research on the field of bioactive materials and functionalization strategies in drug-delivery systems using nanotechnology for pharmaceutic applications. Authors are invited to submit original research articles and reviews in this rapidly expanding research field.

Prof. Dr. Ping-Shan Lai
Prof. Dr. Martin Hsiu-Chu Lin
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

  • controlled drug release
  • drug delivery system
  • nanomedicine
  • targeted drug delivery
  • bioconjugates

Published Papers (7 papers)

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Research

14 pages, 3430 KiB  
Article
Curcumin-Loaded Oil-Free Self-Assembled Micelles Inhibit the Influenza A Virus Activity and the Solidification of Curcumin-Loaded Micelles for Pharmaceutical Applications
by Cun-Zhao Li, Hui-Min Chang, Wei-Li Hsu, Parthiban Venkatesan, Martin Hsiu-Chu Lin and Ping-Shan Lai
Pharmaceutics 2022, 14(11), 2422; https://doi.org/10.3390/pharmaceutics14112422 - 09 Nov 2022
Cited by 4 | Viewed by 1427
Abstract
Curcumin, a well-known natural lipophilic phenolic compound, plays a vital role in inhibiting the influenza infection. Currently, many kinds of formulations for the enhancement of a water dispersion of curcumin have been developed; however, the anti-influenza abilities of formulated curcumin have been much [...] Read more.
Curcumin, a well-known natural lipophilic phenolic compound, plays a vital role in inhibiting the influenza infection. Currently, many kinds of formulations for the enhancement of a water dispersion of curcumin have been developed; however, the anti-influenza abilities of formulated curcumin have been much less investigated. In this study, the optimized self-assembled micelles of RH 40/Tween 80 loaded with curcumin (Cur-M) in an oil-free-based system were spherical with a hydrodynamic size at 13.55 nm ± 0.208 and polydispersity at 0.144 characterized by atomic force microscopy and dynamic light scattering, respectively. Additionally, Cur-M significantly increased the bioactivity/stability of curcumin and effectively inhibited the influenza A virus infection and its replication after viral entry, indicating the alteration of the inhibition mechanisms of curcumin against virus infection via RH 40/Tween 80 micelle formulation. Furthermore, a solid formulation (Cur-SM) of Cur-M was successfully developed by a one-pot physical adsorption method using a small amount of adsorbent and ~50% of curcumin/Cur-M that could be burst released from Cur-SM in 1 h, facilitating the fast-releasing applications. Ultimately, all of the results show that Cur-SM acts as a good nano-formulation of curcumin with improved solubility/dispersity in aqueous solutions and demonstrate new anti-influenza mechanisms of curcumin for pharmaceutical development. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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14 pages, 5341 KiB  
Article
Retention Time Extended by Nanoparticles Improves the Eradication of Highly Antibiotic-Resistant Helicobacter pylori
by Cheng-Jung Yao, Shu-Jyuan Yang, Chung-Huan Huang, Yuan-Ting Chang, Chung-Hao Wang, Ming-Jium Shieh and Tai-Horng Young
Pharmaceutics 2022, 14(10), 2117; https://doi.org/10.3390/pharmaceutics14102117 - 05 Oct 2022
Cited by 1 | Viewed by 1558
Abstract
Helicobacter pylori infection usually causes gastrointestinal complications, including gastrointestinal bleeding or perforation, and serious infections may lead to gastric cancer. Amoxicillin is used to treat numerous bacterial infections but is easily decomposed in the gastric acid environment via the hydrolyzation of the β-lactam [...] Read more.
Helicobacter pylori infection usually causes gastrointestinal complications, including gastrointestinal bleeding or perforation, and serious infections may lead to gastric cancer. Amoxicillin is used to treat numerous bacterial infections but is easily decomposed in the gastric acid environment via the hydrolyzation of the β-lactam ring. In this study, we develop chitosan-based nanoparticles loaded with amoxicillin (CAANs) as an H. pylori eradication platform. The CAANs were biocompatible and could retain the antibiotic activity of amoxicillin against H. pylori growth. The mucoadhesive property of chitosan and alginate enabled the CAANs to adhere to the mucus layers and penetrate through these to release amoxicillin in the space between the layers and the gastric epithelium. The use of this nanoparticle could prolong the retention time and preserve the antibiotic activity of amoxicillin in the stomach and help enhance the eradication rate of H. pylori and reduce treatment time. These CAANs, therefore, show potential for the effective treatment of highly antibiotic-resistant H. pylori infection using amoxicillin. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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17 pages, 5496 KiB  
Article
Evaluation of Topical and Subconjunctival Injection of Hyaluronic Acid-Coated Nanoparticles for Drug Delivery to Posterior Eye
by Cheng-Han Tsai, Le Ngoc Hoang, Chun Che Lin, Liang-Chen Pan, Chiao-Li Wu, I-Chan Lin, Peng-Yuan Wang and Ching-Li Tseng
Pharmaceutics 2022, 14(6), 1253; https://doi.org/10.3390/pharmaceutics14061253 - 13 Jun 2022
Cited by 9 | Viewed by 2706
Abstract
Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an [...] Read more.
Posterior eye diseases, such as age-related macular degeneration and diabetic retinopathy, are difficult to treat due to ineffective drug delivery to affected areas. Intravitreal injection is the primary method for posterior eye drug delivery; however, it is usually accompanied by complications. Therefore, an effective and non-invasive method is required. Self-assembling nanoparticles (NPs) made from gelatin-epigallocatechin gallate (EGCG) were synthesized (GE) and surface-decorated with hyaluronic acid (HA) for drug delivery to the retinal/choroidal area. Different HA concentrations were used to prepare NPs with negative (GEH−) or positive (GEH+) surface charges. The size/zeta potential and morphology of the NPs were characterized by a dynamic light scattering (DLS) system and transmission electron microscope (TEM). The size/zeta potential of GEH+ NPs was 253.4 nm and 9.2 mV. The GEH− NPs were 390.0 nm and −35.9 mV, respectively. The cytotoxicity was tested by adult human retinal pigment epithelial cells (ARPE-19), with the results revealing that variant NPs were non-toxicity at 0.2–50 µg/mL of EGCG, and that the highest amount of GEH+ NPs was accumulated in cells examined by flowcytometry. Topical delivery (eye drops) and subconjunctival injection (SCI) methods were used to evaluate the efficiency of NP delivery to the posterior eyes in a mouse model. Whole eyeball cryosections were used to trace the location of fluorescent NPs in the eyes. The area of fluorescent signal obtained in the posterior eyes treated with GEH+ NPs in both methods (eye drops: 6.89% and SCI: 14.55%) was the greatest when compared with other groups, especially higher than free dye solution (2.79%). In summary, GEH+ NPs can be transported to the retina by eye drops and SCI; in particular, eye drops are a noninvasive method. Furthermore, GEH+ NPs, characterized by a positive surface and HA decoration, could facilitate drug delivery to the posterior eye as a useful drug carrier. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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19 pages, 3988 KiB  
Article
D-Alpha-Tocopheryl Poly(ethylene Glycol 1000) Succinate-Coated Manganese-Zinc Ferrite Nanomaterials for a Dual-Mode Magnetic Resonance Imaging Contrast Agent and Hyperthermia Treatments
by Lin Wang, Syu-Ming Lai, Cun-Zhao Li, Hsiu-Ping Yu, Parthiban Venkatesan and Ping-Shan Lai
Pharmaceutics 2022, 14(5), 1000; https://doi.org/10.3390/pharmaceutics14051000 - 06 May 2022
Cited by 7 | Viewed by 2069
Abstract
Manganese-zinc ferrite (MZF) is known as high-performance magnetic material and has been used in many fields and development. In the biomedical applications, the biocompatible MZF formulation attracted much attention. In this study, water-soluble amphiphilic vitamin E (TPGS, d-alpha-tocopheryl poly(ethylene glycol 1000) succinate) formulated [...] Read more.
Manganese-zinc ferrite (MZF) is known as high-performance magnetic material and has been used in many fields and development. In the biomedical applications, the biocompatible MZF formulation attracted much attention. In this study, water-soluble amphiphilic vitamin E (TPGS, d-alpha-tocopheryl poly(ethylene glycol 1000) succinate) formulated MZF nanoparticles were synthesized to serve as both a magnetic resonance imaging (MRI) contrast agent and a vehicle for creating magnetically induced hyperthermia against cancer. The MZF nanoparticles were synthesized from a metallic acetylacetonate in an organic phase and further modified with TPGS using an emulsion and solvent-evaporation method. The resulting TPGS-modified MZF nanoparticles exhibited a dual-contrast ability, with a longitudinal relaxivity (35.22 s−1 mM Fe−1) and transverse relaxivity (237.94 s−1 mM Fe−1) that were both higher than Resovist®. Furthermore, the TPGS-assisted MZF formulation can be used for hyperthermia treatment to successfully suppress cell viability and tumor growth after applying an alternating current (AC) electromagnetic field at lower amplitude. Thus, the TPGS-assisted MZF theranostics can not only be applied as a potential contrast agent for MRI but also has potential for use in hyperthermia treatments. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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16 pages, 2865 KiB  
Article
Improving Tirapazamine (TPZ) to Target and Eradicate Hypoxia Tumors by Gold Nanoparticle Carriers
by Giimel Ajnai, Chun-Chia Cheng, Tzu-Chun Kan, Jeng-Wei Lu, Sri Rahayu, Amy Chiu and Jungshan Chang
Pharmaceutics 2022, 14(4), 847; https://doi.org/10.3390/pharmaceutics14040847 - 12 Apr 2022
Cited by 8 | Viewed by 2583
Abstract
Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we [...] Read more.
Tumor hypoxia is a hallmark of solid tumors and emerged as the therapeutic target for cancer treatments, such as a prodrug Tirapazamine (TPZ) activated in hypoxia. To increase tumor accumulation, gold nanoparticles (GNPs) were selected to conjugate with TPZ. In this study, we successfully formulated and assessed the biochemical and therapeutic roles of the conjugated gold nanoparticles–Tirapazamine (GNPs–TPZ) on therapeutic assessments of MKN45-induced xenograft animal model. The results indicated that GNPs–TPZ was a potential nanomedicine for selectively targeting hypoxia tumors coupled with decreased side effects on healthy tissue or organs. TPZ significantly reduced cell viability of hypoxic gastric cancer MKN45 cells, but not in cells incubated in normoxia condition. For improving tumor targeting efficiency, furthermore, the GNPs drug carrier was conjugated to TPZ via biding mediator bovine serum albumin (BSA), and we demonstrated that this conjugated GNPs–TPZ retained the unique characteristics of hypoxic toxin and possessed the adequate feature of systemic bio-distributions in animals. GNPs–TPZ nanoparticles revealed their superior affinity to hypoxia tumors in the MKN45 xenograft. Moreover, GNPs–TPZ treatments did not significantly alter the biochemical parameters of blood samples acquired from animals. Taken together, TPZ, a prodrug activated by hypoxia, was conjugated with GNPs, whereas BSA severed as an excellent binding agent for preparing the conjugated GNPs–TPZ nanomedicines. We demonstrated that GNPs–TPZ enhanced tumor targeting, resulting in higher therapeutic efficacy compared to TPZ. We suggest that it may sever as an adjuvant treatment or combined therapy with other chemotherapeutics for the treatment of cancer patients in the future. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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26 pages, 6958 KiB  
Article
Preclinical Therapeutic Assessment of a New Chemotherapeutics [Dichloro(4,4’-Bis(2,2,3,3-Tetrafluoropropoxy) Methyl)-2,2’-Bipryridine) Platinum] in an Orthotopic Patient-Derived Xenograft Model of Triple-Negative Breast Cancers
by Tzu-Chun Kan, Mei-Hsiang Lin, Chun-Chia Cheng, Jeng-Wei Lu, Ming-Thau Sheu, Yuan-Soon Ho, Sri Rahayu and Jungshan Chang
Pharmaceutics 2022, 14(4), 839; https://doi.org/10.3390/pharmaceutics14040839 - 11 Apr 2022
Cited by 2 | Viewed by 2294
Abstract
Cisplatin is one of the most common therapeutics used in treatments of several types of cancers. To enhance cisplatin lipophilicity and reduce resistance and side effects, a polyfluorinated bipyridine-modified cisplatin analogue, dichloro[4,4’-bis(2,2,3,3-tetrafluoropropoxy)methyl)-2,2’-bipryridine] platinum (TFBPC), was synthesized and therapeutic assessments were performed. TFBPC displayed [...] Read more.
Cisplatin is one of the most common therapeutics used in treatments of several types of cancers. To enhance cisplatin lipophilicity and reduce resistance and side effects, a polyfluorinated bipyridine-modified cisplatin analogue, dichloro[4,4’-bis(2,2,3,3-tetrafluoropropoxy)methyl)-2,2’-bipryridine] platinum (TFBPC), was synthesized and therapeutic assessments were performed. TFBPC displayed superior effects in inhibiting the proliferation of several cisplatin-resistant human cancer cell lines, including MDA-MB-231 breast cancers, COLO205 colon cancers and SK-OV-3 ovarian cancers. TFBPC bound to DNA and formed DNA crosslinks that resulted in DNA degradation, triggering the cell death program through the PARP/Bax/Bcl-2 apoptosis and LC3-related autophagy pathway. Moreover, TFBPC significantly inhibited tumor growth in both animal models which include a cell line-derived xenograft model (CDX) of cisplatin-resistant MDA-MB-231, and a patient-derived xenograft (PDX) model of triple-negative breast cancers (TNBCs). Furthermore, the biopsy specimen from TFBPC-treated xenografts revealed decreased expressions of P53, Ki-67 and PD-L1 coupled with higher expression of cleaved caspase 3, suggesting TFBPC treatment was effective and resulted in good prognostic indications. No significant pathological changes were observed in hematological and biochemistry tests in blood and histological examinations from the specimen of major organs. Therefore, TFBPC is a potential candidate for treatments of patients suffering from TNBCs as well as other cisplatin-resistant cancers. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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15 pages, 11006 KiB  
Article
Dual-Functional Polymeric Micelles Co-Loaded with Antineoplastic Drugs and Tyrosine Kinase Inhibitor for Combination Therapy in Colorectal Cancer
by Ying-Hsia Shih, Cheng-Liang Peng, Ping-Fang Chiang and Ming-Jium Shieh
Pharmaceutics 2022, 14(4), 768; https://doi.org/10.3390/pharmaceutics14040768 - 31 Mar 2022
Cited by 3 | Viewed by 1741
Abstract
The aim of this research was to evaluate the receptor tyrosine kinase inhibitor Sunitinib combined with SN-38 in polymeric micelles for antitumor efficacy in colorectal cancer. First, SN-38 and Sunitinib co-loaded micelles were developed and characterized. We studied cell viability and cellular uptake [...] Read more.
The aim of this research was to evaluate the receptor tyrosine kinase inhibitor Sunitinib combined with SN-38 in polymeric micelles for antitumor efficacy in colorectal cancer. First, SN-38 and Sunitinib co-loaded micelles were developed and characterized. We studied cell viability and cellular uptake in HCT-116 cells. Then, subcutaneous HCT-116 xenograft tumors were used for ex vivo biodistribution, antitumor efficacy, and histochemical analysis studies. Results of cellular uptake and ex vivo biodistribution of SN-38/Sunitinib micelles showed the highest accumulation in tumors compared with other normal organs. In the antitumor effect studies, mice bearing HCT-116 tumors were smallest at day 28 after injection of SN-38/Sunitinib micelles, compared with other experiment groups (p < 0.01). As demonstrated by the results of inhibition on multi-receptors by Sunitinib, we confirmed that SN-38/Sunitinib co-loaded micelles to be a treatment modality that could inhibit VEGF and PDGF receptors and enhance the antitumor effect of SN-38 (p < 0.05). In summary, we consider that this micelle is a potential formulation for the combination of SN-38 and Sunitinib in the treatment of colorectal cancer. Full article
(This article belongs to the Special Issue Bioactive Materials in Drug-Delivery Systems)
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