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Pharmaceutics
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Nanoformulation of Drug Delivery Systems for Natural Products
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Nanoformulation of Drug Delivery Systems for Natural Products

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

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 22847

Special Issue Editors

Prof. Dr. Jyrki Heinämäki

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Guest Editor
Institute of Pharmacy, Faculty of Medicine, University of Tartu, Nooruse 1, EE-50411 Tartu, Estonia
Interests: pharmaceutical nanotechnology; nanofibers; electrospinning; liposomes; oral drug delivery; poorly water-soluble drugs; nanoformulation of natural products; polymer coatings; process analytical technology (PAT); pharmaceutical 3D printing; wound healing systems
Prof. Dr. Ain Raal

E-Mail Website
Guest Editor
Institute of Pharmacy, Faculty of Medicine, University of Tartu, 50411 Tartu, Estonia
Interests: pharmacy; pharmacognosy; phytochemistry; phytotherapy; ethnomedicine; ethnobotany; history of pharmacy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pharmaceutical nanotechnology is an emerging area of science that combines nanotechnology with pharmaceutical and biomedical sciences and focuses on improved medicines through the design, formulation and characterisation of nanotechnology-based drug delivery systems (DDSs). Today, the interest in applying novel nanotechnology strategies for the formulation of natural products (i.e., for the active ingredients or extracts originating from plants, minerals or animals) is steadily increasing due to the well-documented benefits associated with the use of such DDSs. It is evident that new nanotechnology-based DDSs provide, for example, improvements in the therapeutic efficiency of native-origin active ingredients, the reduction of dose and adverse effects, and improvements in the stability of the final product. The aim of the present Special Issue is to provide a publication platform for research works presenting the recent advancements in the integration of pharmaceutical nanotechnology with natural products in developing modern DDSs. The advanced pharmaceutical nanocarrier systems integrated with natural products could be (but are not limited to) polymeric nanoparticles, solid lipid nanoparticles, liposomes, nanocrystals, nanofibers, polymersomes, exosomes, nanomicelles, dendrimers, quantum dots, and carbon nanotubes. Such nanotechnology-based DDSs could be designed for gastrointestinal delivery, topical skin (wound) and transdermal delivery, parenteral delivery, ocular delivery, pulmonary delivery, rectal delivery and theranostics applications, among others.

Prof. Dr. Jyrki Heinämäki
Prof. Dr. Ain Raal
Guest Editors

Manuscript Submission Information

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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

  • pharmaceutical nanotechnology
  • nanoformulation
  • natural products
  • medicinal plant products
  • herbal extracts
  • native-origin actives
  • actives of animal origin
  • drug delivery systems
  • nanoparticulate systems
  • biological activity

Published Papers (9 papers)

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Research

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17 pages, 4752 KiB  
Article
Investigating the Effectiveness of Different Porous Nanoparticles as Drug Carriers for Retaining the Photostability of Pinosylvin Derivative
by Fadak Howaili, Atefeh Saadabadi, Ermei Mäkilä, Ekaterina Korotkova, Patrik C. Eklund, Outi M. H. Salo-Ahen and Jessica M. Rosenholm
Pharmaceutics 2024, 16(2), 276; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics16020276 - 15 Feb 2024
Viewed by 889
Abstract
Pinosylvin monomethyl ether (PsMME) is a natural compound known for its valuable bioactive properties, including antioxidant and anti-inflammatory effects. However, PsMME’s susceptibility to photodegradation upon exposure to ultraviolet (UV) radiation poses a significant limitation to its applications in the pharmaceutical field. This study, [...] Read more.
Pinosylvin monomethyl ether (PsMME) is a natural compound known for its valuable bioactive properties, including antioxidant and anti-inflammatory effects. However, PsMME’s susceptibility to photodegradation upon exposure to ultraviolet (UV) radiation poses a significant limitation to its applications in the pharmaceutical field. This study, for the first time, introduces a strategy to enhance the photostability of PsMME by employing various nanoformulations. We utilized mesoporous silica nanoparticles (MSNs) coated with polydopamine via a poly(ethylene imine) layer (PDA–PEI–MSNs), thermally carbonized porous silicon nanoparticles (TCPSi), and pure mesoporous polydopamine nanoparticles (MPDA). All these nanocarriers exhibit unique characteristics, including the potential for shielding the drug from UV light, which makes them promising for enhancing the photostability of loaded drugs. Here, these three nanoparticles were synthesized and their morphological and physicochemical properties, including size and ζ-potential, were characterized. They were subsequently loaded with PsMME, and the release profiles and kinetics of all three nanoformulations were determined. To assess their photoprotection ability, we employed gas chromatography with a flame ionization detector (GC-FID) and gas chromatography–mass spectrometry (GC-MS) to assess the recovery percentage of loaded PsMME before and after UV exposure for each nanoformulation. Our findings reveal that MPDA exhibits the highest protection ability, with a remarkable 90% protection against UV light on average. This positions MPDA as an ideal carrier for PsMME, and by extension, potentially for other photolabile drugs as well. As a final confirmation of its suitability as a drug nanocarrier, we conducted cytotoxicity evaluations of PsMME-loaded MPDA, demonstrating dose-dependent drug toxicity for this formulation. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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13 pages, 2431 KiB  
Article
In Vitro and In Vivo Evaluation of Inhalable Ciprofloxacin Sustained Release Formulations
by Changzhi Shi, Kewei Guo, Li Zhang, Yi Guo, Yu Feng, Sandra Cvijić, Dongmei Cun and Mingshi Yang
Pharmaceutics 2023, 15(9), 2287; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15092287 - 06 Sep 2023
Cited by 1 | Viewed by 1007
Abstract
Respiratory antibiotics delivery has been appreciated for its high local concentration at the infection sites. Certain formulation strategies are required to improve pulmonary drug exposure and to achieve effective antimicrobial activity, especially for highly permeable antibiotics. This study aimed to investigate lung exposure [...] Read more.
Respiratory antibiotics delivery has been appreciated for its high local concentration at the infection sites. Certain formulation strategies are required to improve pulmonary drug exposure and to achieve effective antimicrobial activity, especially for highly permeable antibiotics. This study aimed to investigate lung exposure to various inhalable ciprofloxacin (CIP) formulations with different drug release rates in a rat model. Four formulations were prepared, i.e., CIP-loaded PLGA micro-particles (CHPM), CIP microcrystalline dry powder (CMDP), CIP nanocrystalline dry powder (CNDP), and CIP spray-dried powder (CHDP), which served as a reference. The physicochemical properties, drug dissolution rate, and aerosolization performance of these powders were characterized in vitro. Pharmacokinetic profiles were evaluated in rats. All formulations were suitable for inhalation (mass median aerodynamic diameter < 5 µm). CIP in CHPM and CHDP was amorphous, whereas the drug in CMDP and CNDP remained predominantly crystalline. CHDP exhibited the fastest drug release rate, while CMDP and CNDP exhibited much slower drug release. In addition, CMDP and CNDP exhibited significantly higher in vivo lung exposure to CIP compared with CHDP and CHPM. This study suggests that lung exposure to inhaled drugs with high permeability is governed by drug release rate, implying that lung exposure of inhaled antibiotics could be improved by a sustained-release formulation strategy. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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16 pages, 2782 KiB  
Article
New Approach for Preparing Solid Lipid Nanoparticles with Volatile Oil-Loaded Quercetin Using the Phase-Inversion Temperature Method
by Yotsanan Weerapol, Suwisit Manmuan, Nattaya Chaothanaphat, Sontaya Limmatvapirat, Jitnapa Sirirak, Poomipat Tamdee and Sukannika Tubtimsri
Pharmaceutics 2022, 14(10), 1984; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14101984 - 20 Sep 2022
Cited by 9 | Viewed by 2218
Abstract
Quercetin (QCT), a natural flavonoid, is of research interest owing to its pharmacological properties. However, its pharmacokinetic limitations could hinder its widespread therapeutic use. Nanocarriers, especially solid lipid nanoparticles (SLNs), might overcome this constraint. This study aimed to investigate QCT-loaded SLNs prepared via [...] Read more.
Quercetin (QCT), a natural flavonoid, is of research interest owing to its pharmacological properties. However, its pharmacokinetic limitations could hinder its widespread therapeutic use. Nanocarriers, especially solid lipid nanoparticles (SLNs), might overcome this constraint. This study aimed to investigate QCT-loaded SLNs prepared via a new approach using a volatile oil. The phase-inversion temperature method was used to incorporate rosemary oil (RMO) into SLNs prepared using solid lipids possessing different chemical structures. Among the solid lipids used in the formulations, trilaurin (TLR) exhibited the smallest particle size and good stability after a temperature cycling test. SLNs prepared with a ratio of RMO to TLR of 1:3 could load QCT with an entrapment efficiency of >60% and drug loading of ~2% w/w. The smallest particle size was achieved using the polyoxyethylene-hydrogenated castor oil RH40, and the particle size depended on the concentration. The drug-release profile of QCT_TLR exhibited prolonged biphasic release for >24 h. QCT_TLR was a safe formulation, as indicated by a cell viability percentage of >75% at <2% v/v. In a computer simulation, the system with RMO enabled smaller sized SLNs than those without RMO. This new discovery shows great promise for producing SLNs via the phase-inversion temperature method with incorporation of volatile oil, particularly for delivering compounds with limited water solubility. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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19 pages, 7666 KiB  
Article
Reparative Efficacy of Liposome-Encapsulated Oleanolic Acid against Liver Inflammation Induced by Fine Ambient Particulate Matter and Alcohol in Mice
by Ching-Ting Wei, Yu-Wen Wang, Yu-Chiuan Wu, Li-Wei Lin, Chia-Chi Chen, Chun-Yin Chen and Shyh-Ming Kuo
Pharmaceutics 2022, 14(5), 1108; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14051108 - 23 May 2022
Cited by 3 | Viewed by 2351
Abstract
Airborne fine particulate matter (PM2.5) is a severe problem and is associated with health issues including liver diseases. Workers performing manual labor tend to be alcohol consumers during work, where they are also exposed to PM2.5. Long-term PM2.5 [...] Read more.
Airborne fine particulate matter (PM2.5) is a severe problem and is associated with health issues including liver diseases. Workers performing manual labor tend to be alcohol consumers during work, where they are also exposed to PM2.5. Long-term PM2.5 exposure can increase oxidative stress, leading to inflammation. Whether long-term exposure to air pollution and alcohol synergistically increases liver fibrosis risk warrants investigation. Oleanolic acid (OA)—a triterpenoid—has antioxidant and anti-inflammatory activities, but its low water solubility and cytotoxicity impair its potential applications. In this study, we fabricated liposomal OA nanoparticles (Lipo-OAs); then, we evaluated the anti-inflammatory effect on exposed cells and the ameliorative effect of Lipo-OAs on PM2.5 and alcohol-induced liver fibrosis in mice. The half maximal inhibitory concentration of PM2.5 for hepatic stellate cells was 900 μg/mL; at a concentration of ≥600 μg/mL, PM2.5 significantly increased interleukin-6 and tumor necrosis factor-α production. OA encapsulation in Lipo-OAs, 353 ± 140 nm in diameter with 79% encapsulation efficiency, significantly reduced OA cytotoxicity. Lipo-OAs treatment significantly reduced alanine aminotransferase, aspartate aminotransferase, and γ-glutamyltransferase levels; histologically, it alleviated steatosis and improved Ishak’s modified HAI score. In conclusion, Lipo-OAs have potential anti-inflammatory and reparative effects for PM2.5 and alcohol-induced liver injury treatment. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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15 pages, 3377 KiB  
Article
The Binding of Alpinia galanga Oil and Its Nanoemulsion to Mammal GABAA Receptors Using Rat Cortical Membranes and an In Silico Modeling Platform
by Nattakanwadee Khumpirapang, Krit Suknuntha, Pathomwat Wongrattanakamon, Supat Jiranusornkul, Songyot Anuchapreeda, Petrine Wellendorph, Anette Müllertz, Thomas Rades and Siriporn Okonogi
Pharmaceutics 2022, 14(3), 650; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14030650 - 16 Mar 2022
Cited by 1 | Viewed by 1812
Abstract
The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its pathway in mammals is limited. In the present study, the binding of AGO and its key compounds, methyl eugenol, 1,8-cineole, and 4-allylphenyl acetate, to gamma-aminobutyric acid type A [...] Read more.
The anesthetic effect of Alpinia galanga oil (AGO) has been reported. However, knowledge of its pathway in mammals is limited. In the present study, the binding of AGO and its key compounds, methyl eugenol, 1,8-cineole, and 4-allylphenyl acetate, to gamma-aminobutyric acid type A (GABAA) receptors in rat cortical membranes, was investigated using a [3H]muscimol binding assay and an in silico modeling platform. The results showed that only AGO and methyl eugenol displayed a positive modulation at the highest concentrations, whereas 1,8-cineole and 4-allylphenyl acetate were inactive. The result of AGO correlated well to the amount of methyl eugenol in AGO. Computational docking and dynamics simulations into the GABAA receptor complex model (PDB: 6X3T) showed the stable structure of the GABAA receptor–methyl eugenol complex with the lowest binding energy of −22.16 kcal/mol. This result shows that the anesthetic activity of AGO and methyl eugenol in mammals is associated with GABAA receptor modulation. An oil-in-water nanoemulsion containing 20% w/w AGO (NE-AGO) was formulated. NE-AGO showed a significant increase in specific [3H]muscimol binding, to 179% of the control, with an EC50 of 391 µg/mL. Intracellular studies show that normal human cells are highly tolerant to AGO and the nanoemulsion, indicating that NE-AGO may be useful for human anesthesia. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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Review

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39 pages, 6116 KiB  
Review
More Than Pigments: The Potential of Astaxanthin and Bacterioruberin-Based Nanomedicines
by Maria Jose Morilla, Kajal Ghosal and Eder Lilia Romero
Pharmaceutics 2023, 15(7), 1828; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15071828 - 26 Jun 2023
Cited by 9 | Viewed by 2107
Abstract
Carotenoids are natural products regulated by the food sector, currently used as feed dyes and as antioxidants in dietary supplements and composing functional foods for human consumption. Of the nearly one thousand carotenoids described to date, only retinoids, derived from beta carotene, have [...] Read more.
Carotenoids are natural products regulated by the food sector, currently used as feed dyes and as antioxidants in dietary supplements and composing functional foods for human consumption. Of the nearly one thousand carotenoids described to date, only retinoids, derived from beta carotene, have the status of a drug and are regulated by the pharmaceutical sector. In this review, we address a novel field: the transformation of xanthophylls, particularly the highly marketed astaxanthin and the practically unknown bacterioruberin, in therapeutic agents by altering their pharmacokinetics, biodistribution, and pharmacodynamics through their formulation as nanomedicines. The antioxidant activity of xanthophylls is mediated by routes different from those of the classical oral anti-inflammatory drugs such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAIDs): remarkably, xanthophylls lack therapeutic activity but also lack toxicity. Formulated as nanomedicines, xanthophylls gain therapeutic activity by mechanisms other than increased bioavailability. Loaded into ad hoc tailored nanoparticles to protect their structure throughout storage and during gastrointestinal transit or skin penetration, xanthophylls can be targeted and delivered to selected inflamed cell groups, achieving a massive intracellular concentration after endocytosis of small doses of formulation. Most first reports showing the activities of oral and topical anti-inflammatory xanthophyll-based nanomedicines against chronic diseases such as inflammatory bowel disease, psoriasis, atopic dermatitis, and dry eye disease emerged between 2020 and 2023. Here we discuss in detail their preclinical performance, mostly targeted vesicular and polymeric nanoparticles, on cellular models and in vivo. The results, although preliminary, are auspicious enough to speculate upon their potential use for oral or topical administration in the treatment of chronic inflammatory diseases. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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20 pages, 2585 KiB  
Review
Naringin: Nanotechnological Strategies for Potential Pharmaceutical Applications
by Soledad Ravetti, Ariel G. Garro, Agustina Gaitán, Mariano Murature, Mariela Galiano, Sofía G. Brignone and Santiago D. Palma
Pharmaceutics 2023, 15(3), 863; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics15030863 - 07 Mar 2023
Cited by 10 | Viewed by 2734
Abstract
Polyphenols comprise a number of natural substances, such as flavonoids, that show interesting biological effects. Among these substances is naringin, a naturally occurring flavanone glycoside found in citrus fruits and Chinese medicinal herbs. Several studies have shown that naringin has numerous biological properties, [...] Read more.
Polyphenols comprise a number of natural substances, such as flavonoids, that show interesting biological effects. Among these substances is naringin, a naturally occurring flavanone glycoside found in citrus fruits and Chinese medicinal herbs. Several studies have shown that naringin has numerous biological properties, including cardioprotective, cholesterol-lowering, anti-Alzheimer’s, nephroprotective, antiageing, antihyperglycemic, antiosteoporotic and gastroprotective, anti-inflammatory, antioxidant, antiapoptotic, anticancer and antiulcer effects. Despite its multiple benefits, the clinical application of naringin is severely restricted due to its susceptibility to oxidation, poor water solubility, and dissolution rate. In addition, naringin shows instability at acidic pH, is enzymatically metabolized by β-glycosidase in the stomach and is degraded in the bloodstream when administered intravenously. These limitations, however, have been overcome thanks to the development of naringin nanoformulations. This review summarizes recent research carried out on strategies designed to improve naringin’s bioactivity for potential therapeutic applications. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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24 pages, 1487 KiB  
Review
Essential Oil—Loaded Nanofibers for Pharmaceutical and Biomedical Applications: A Systematic Mini-Review
by Ioannis Partheniadis, Georgios Stathakis, Dimitra Tsalavouti, Jyrki Heinämäki and Ioannis Nikolakakis
Pharmaceutics 2022, 14(9), 1799; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14091799 - 26 Aug 2022
Cited by 11 | Viewed by 2223
Abstract
Essential oils (EOs) have been widely exploited for their biological properties (mainly as antimicrobials) in the food industry. Encapsulation of EOs has opened the way to the utilization of EOs in the pharmaceutical and biomedical fields. Electrospinning (ES) has proved a convenient and [...] Read more.
Essential oils (EOs) have been widely exploited for their biological properties (mainly as antimicrobials) in the food industry. Encapsulation of EOs has opened the way to the utilization of EOs in the pharmaceutical and biomedical fields. Electrospinning (ES) has proved a convenient and versatile method for the encapsulation of EOs into multifunctional nanofibers. Within the last five years (2017–2022), many research articles have been published reporting the use of ES for the fabrication of essential oil—loaded nanofibers (EONFs). The objective of the present mini-review article is to elucidate the potential of EONFs in the pharmaceutical and biomedical fields and to highlight their advantages over traditional polymeric films. An overview of the conventional ES and coaxial ES technologies for the preparation of EONFs is also included. Even though EONFs are promising systems for the delivery of EOs, gaps in the literature can be recognized (e.g., stability studies) emphasizing that more research work is needed in this field to fully unravel the potential of EONFs. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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27 pages, 6784 KiB  
Review
Bioactive Loaded Novel Nano-Formulations for Targeted Drug Delivery and Their Therapeutic Potential
by Sapna Kumari, Anju Goyal, Eda Sönmez Gürer, Evren Algın Yapar, Madhukar Garg, Meenakshi Sood and Rakesh K. Sindhu
Pharmaceutics 2022, 14(5), 1091; https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics14051091 - 19 May 2022
Cited by 33 | Viewed by 5596
Abstract
Plant-based medicines have received a lot of attention in recent years. Such medicines have been employed to treat medical conditions since ancient times, and in those times only the observed symptoms were used to determine dose accuracy, dose efficacy, and therapy. Rather than [...] Read more.
Plant-based medicines have received a lot of attention in recent years. Such medicines have been employed to treat medical conditions since ancient times, and in those times only the observed symptoms were used to determine dose accuracy, dose efficacy, and therapy. Rather than novel formulations, the current research work on plant-based medicines has mostly concentrated on medicinal active phytoconstituents. In the past recent decades, however, researchers have made significant progress in developing “new drug delivery systems” (NDDS) to enhance therapeutic efficacy and reduce unwanted effects of bioactive compounds. Nanocapsules, polymer micelles, liposomes, nanogels, phytosomes, nano-emulsions, transferosomes, microspheres, ethosomes, injectable hydrogels, polymeric nanoparticles, dendrimers, and other innovative therapeutic formulations have all been created using bioactive compounds and plant extracts. The novel formulations can improve solubility, therapeutic efficacy, bioavailability, stability, tissue distribution, protection from physical and chemical damage, and prolonged and targeted administration, to name a few. The current study summarizes existing research and the development of new formulations, with a focus on herbal bioactive components. Full article
(This article belongs to the Special Issue Nanoformulation of Drug Delivery Systems for Natural Products)
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