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Nanoencapsulation Strategies for Active Compounds Delivery

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A special issue of Nanomaterials (ISSN 2079-4991). This special issue belongs to the section "Biology and Medicines".

Deadline for manuscript submissions: closed (8 October 2021) | Viewed by 39863

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Prof. Dr. Claudia Carbone

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1. Department of Drug and Health Sciences, University of Catania, Catania, Italy
2. NANOMED-Research Centre on Nanomedicine and Pharmaceutical Nanotechnology, University of Catania, Catania, Italy
Interests: drug delivery; nanomedicine; nutraceuticals; pharmaceutical technology; natural compounds
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Carla Caddeo

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Guest Editor

Department di Scienze della Vita e dell’Ambiente, University of Cagliari, 09124 Cagliari, Italy
Interests: drug delivery nanosystems for pharmaceutical, cosmetic, and nutraceutical applications: design, optimization, preparation, and characterization; dermal/transdermal drug delivery; intestinal drug delivery; oral drug delivery; delivery of bioactive natural compounds
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Teresa Musumeci

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Guest Editor

Department of Drug Sciences, Università degli Studi di Catania, 95131 Catania, Italy
Interests: drug delivery systems for pharmaceutical, cosmetic and agro-food applications: design, optimization, preparation and characterization; nose to brain delivery; ophthalmic drug delivery; new biodegradable polymers for drug delivery systems; nanomedicine for cancer diagnosis and therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Nanoencapsulation strategies represent a hot topic of great interest, since they provide increasing drug therapeutic effectiveness (overcoming solubility, stability and bioavailability problems) of low soluble drugs (BCS class II and IV) and non-Lipinski compounds. Nanoencapsulation promotes drug repurposing (a cost-effective and timesaving identification of novel pharmacological effects of conventional drugs) and the use of natural compounds, a promising reservoir for human health.

The interest in the nanoencapsulation of active molecules also continues due to the need to account for several drawbacks, in particular those related to customization, patient compliance, impact on human health and environment, fields of application (pharmaceutical, cosmetic, agro-food).

This Special Issue invites manuscripts concerning the nanoencapsulation of synthetic drugs, peptides, proteins and natural compounds, with a particular emphasis on their applications in targeted and controlled delivery. Original articles on nanoencapsulation strategies will be considered, including the use of different structures (nanoparticles, vesicles, supramolecular drug delivery systems), materials (lipids, polymers, hybrid nanoparticles, etc), combining drugs encapsulation strategies (dual delivery) and the use of different coating materials. In vitro and in vivo studies are recommended.

Prof. Dr. Claudia Carbone
Prof. Dr. Claudia Carbone
Prof. Dr. Teresa Musumeci
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. Nanomaterials is an international peer-reviewed open access semimonthly 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

nanoparticles
nanocarriers
drug delivery systems
hybrid nanoparticles
coating strategies
liposomes
dual delivery
synthetic drugs
natural compounds

Published Papers (11 papers)

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Editorial

Jump to: Research, Review

2 pages, 158 KiB

Open AccessEditorial

Nanoencapsulation Strategies for Active Compounds Delivery

by Claudia Carbone, Carla Caddeo and Teresa Musumeci

Nanomaterials 2022, 12(8), 1319; https://doi.org/10.3390/nano12081319 - 12 Apr 2022

Cited by 1 | Viewed by 1068

Abstract

Nanoencapsulation strategies, including the possibility to deliver natural compounds, synthetic molecules, or other actives (viruses) for the treatment of different human diseases, represent a hot topic of great interest [...] Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

Research

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18 pages, 8931 KiB

Open AccessArticle

Challenges in Coopted Hydrophilic and Lipophilic Herbal Bioactives in the Same Nanostructured Carriers for Effective Bioavailability and Anti-Inflammatory Action

by Teodora-Alexandra Iordache, Nicoleta Badea, Mirela Mihaila, Simona Crisan, Anca Lucia Pop and Ioana Lacatusu

Nanomaterials 2021, 11(11), 3035; https://doi.org/10.3390/nano11113035 - 12 Nov 2021

Cited by 4 | Viewed by 1712

Abstract

There is ongoing research on various herbal bioactives and delivery systems which indicates that both lipid nanocarriers and herbal medicines will be fine tunned and integrated for future bio-medical applications. The current study was undertaken to systematically develop NLC-DSG-yam extract for the improved efficacy of herbal Diosgenin (DSG) in the management of anti-inflammatory disorders. NLCs were characterized regarding the mean size of the particles, morphological characteristics, physical stability in time, thermal behaviour, and entrapment efficiency of the herbal bioactive. Encapsulation efficiency and in vitro antioxidant activity measured the differences between the individual and dual co-loaded-NLC, the co-loaded one assuring a prolonged controlled release of DSG and a more emphasized ability of capturing short-life reactive oxygen species (ROS). NLCs safety properties were monitored following the in vitro MTS ((3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium reduction assay) and RTCA (Real-Time Cell Analysis) assays. Concentrations less than 50 μg/mL showed no cytotoxic effects during in vitro cytotoxicity assays. Besides, the NLC-DSG-yam extract revealed a great anti-inflammatory effect, as the production of pro-inflammatory cytokines (TNF-alpha, IL-6) was significantly inhibited at 50 μg/mL NLC (e.g., 98.2% ± 1.07 inhibition of TNF-α, while for IL-6 the inhibition percentage was of 62% ± 1.07). Concluding, using appropriate lipid nanocarriers, the most desirable properties of herbal bioactives could be improved. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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22 pages, 7734 KiB

Open AccessArticle

Mono- and Dicationic DABCO/Quinuclidine Composed Nanomaterials for the Loading of Steroidal Drug: 3² Factorial Design and Physicochemical Characterization

by Ana R. Fernandes, Elena Sanchez-Lopez, Antonello Santini, Tiago dos Santos, Maria L. Garcia, Amélia M. Silva and Eliana B. Souto

Nanomaterials 2021, 11(10), 2758; https://doi.org/10.3390/nano11102758 - 18 Oct 2021

Cited by 9 | Viewed by 2077

Abstract

Oil-in-water nanoemulsions (NEs) are considered a suitable nanotechnological approach to improve the eye-related bioavailability of lipophilic drugs. The potential of cationic NEs is prominent due to the electrostatic interaction that occurs between the positively charged droplets with the negatively charged mucins present in the tear film. This interaction offers prolonged NEs residence at the ocular surface, increasing the drug absorption. Triamcinolone acetonide (TA) is one of the first pharmacologic strategies applied as an intravitreal injection in the treatment of age-related macular degeneration (AMD). Newly synthesized quaternary derivatives of 1,4-diazabicyclo[2.2.2]octane (DABCO) and quinuclidine surfactants have been screened with the purpose to select the best compound to formulate long-term stable NEs that combine the best physicochemical properties for the loading of TA intended for ocular administration. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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16 pages, 2695 KiB

Open AccessArticle

Improvement of Ferulic Acid Antioxidant Activity by Multiple Emulsions: In Vitro and In Vivo Evaluation

by Antonia Mancuso, Maria Chiara Cristiano, Rosanthony Pandolfo, Manfredi Greco, Massimo Fresta and Donatella Paolino

Nanomaterials 2021, 11(2), 425; https://doi.org/10.3390/nano11020425 - 08 Feb 2021

Cited by 19 | Viewed by 3088

Abstract

Ferulic acid is a derivative of cinnamic acid showing efficacious anti-oxidant activity. It catalyzes the stable phenoxy radical formation, upon absorption of ultraviolet light, giving the strength to ferulic acid for terminating free radical chain reactions. Ultraviolet rays are one of the most dangerous factors that daily assault the skin, causing excessive generation of reactive oxygen species (ROS), which are regarded to be important contributors to a variety of cutaneous alterations. The skin possesses endogenous antioxidant defense systems, but the excess of ROS leads to an oxidant–antioxidant imbalance. Although ferulic acid is daily introduced in human organism with the diet, its bioavailability after oral administration is poor, particularly in the skin. The aim of this investigation was to evaluate three types of emulsions (W/O/W multiple emulsions and two simple emulsions) as suitable formulations for topical application of the active compound. In vitro studies were performed to investigate the stability and release profiles of these systems. Multiple emulsions showed great stability and the best ability to carry and release ferulic acid. In vivo evaluations highlighted their best capability to treat UV-B-induced erythema. These findings suggested multiple emulsions as an innovative and more efficient vehicle for topical application of ferulic acid. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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17 pages, 3181 KiB

Open AccessArticle

Astaxanthin-Loaded Stealth Lipid Nanoparticles (AST-SSLN) as Potential Carriers for the Treatment of Alzheimer’s Disease: Formulation Development and Optimization

by Debora Santonocito, Giuseppina Raciti, Agata Campisi, Giovanni Sposito, Annamaria Panico, Edy Angela Siciliano, Maria Grazia Sarpietro, Elisabetta Damiani and Carmelo Puglia

Nanomaterials 2021, 11(2), 391; https://doi.org/10.3390/nano11020391 - 03 Feb 2021

Cited by 35 | Viewed by 3028 | Correction

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder associated with marked oxidative stress at the level of the brain. Recent studies indicate that increasing the antioxidant capacity could represent a very promising therapeutic strategy for AD treatment. Astaxanthin (AST), a powerful natural antioxidant, could be a good candidate for AD treatment, although its use in clinical practice is compromised by its high instability. In order to overcome this limit, our attention focused on the development of innovative AST-loaded stealth lipid nanoparticles (AST-SSLNs) able to improve AST bioavailability in the brain. AST-SSLNs prepared by solvent-diffusion technique showed technological parameters suitable for parenteral administration (<200 nm). Formulated nanosystems were characterized by calorimetric studies, while their toxicological profile was evaluated by the MTT assay on the stem cell line OECs (Olfactory Ensheathing Cells). Furthemore, the protective effect of the nanocarriers was assessed by a long-term stability study and a UV stability assay confirming that the lipid shell of the nanocarriers was able to preserve AST concentration in the formulation. SSLNs were also capable of preserving AST’s antioxidant capacity as demonstrated in the oxygen radical absorbance capacity (ORAC) assay. In conclusion, these preliminary studies outline that SSLNs could be regarded as promising carriers for systemic administration of compounds such as AST aimed at AD treatment. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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21 pages, 2031 KiB

Open AccessFeature PaperArticle

Curcumin Loaded Polymeric vs. Lipid Nanoparticles: Antioxidant Effect on Normal and Hypoxic Olfactory Ensheathing Cells

by Angela Bonaccorso, Rosalia Pellitteri, Barbara Ruozi, Carmelo Puglia, Debora Santonocito, Rosario Pignatello and Teresa Musumeci

Nanomaterials 2021, 11(1), 159; https://doi.org/10.3390/nano11010159 - 10 Jan 2021

Cited by 17 | Viewed by 2810

Abstract

Background: Curcumin (Cur) shows anti-inflammatory and antioxidant effects on central nervous system diseases. The aim of this study was to develop Cur-loaded polymeric and lipid nanoparticles for intranasal delivery to enhance its stability and increase antioxidant effect on olfactory ensheathing cells (OECs). Methods: The nanosuspensions were subjected to physico-chemical and technological evaluation through photon correlation spectroscopy (PCS), differential scanning calorimetry (DSC) and UV-spectrophotometry. The cytotoxicity studies of nanosuspensions were carried out on OECs. A viability test was performed after 24 h of exposure of OECs to unloaded and curcumin-loaded nanosuspensions. The potential protective effect of Cur was assessed on hypoxic OECs cells. Uptake studies were performed on the same cell cultures. Thermal analysis was performed to evaluate potential interaction of Cur with a 1,2-Dimyristoyl-sn-glycero-3-phosphocholine (DMPC) biomembrane model. Results: PCS analysis indicated that lipid and polymeric nanosuspensions showed a mean size of 127.10 and 338.20 nm, respectively, high homogeneity and negative zeta potential. Incorporation of Cur into both nanocarriers increased drug stability up to 135 days in cryoprotected freeze-dried nanosuspensions. Cell viability was improved when hypoxic OECs were treated with Cur-loaded polymeric and lipid nanosuspensions compared with the control. Conclusions: Both nanocarriers could improve the stability of Cur as demonstrated by technological studies. Biological studies revealed that both nanocarriers could be used to deliver Cur by intranasal administration for brain targeting. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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20 pages, 4826 KiB

Open AccessArticle

Development of a New Hyaluronic Acid Based Redox-Responsive Nanohydrogel for the Encapsulation of Oncolytic Viruses for Cancer Immunotherapy

by Siyuan Deng, Alessandra Iscaro, Giorgia Zambito, Yimin Mijiti, Marco Minicucci, Magnus Essand, Clemens Lowik, Munitta Muthana, Roberta Censi, Laura Mezzanotte and Piera Di Martino

Nanomaterials 2021, 11(1), 144; https://doi.org/10.3390/nano11010144 - 08 Jan 2021

Cited by 25 | Viewed by 4216

Abstract

Oncolytic viruses (OVs) are emerging as promising and potential anti-cancer therapeutic agents, not only able to kill cancer cells directly by selective intracellular viral replication, but also to promote an immune response against tumor. Unfortunately, the bioavailability under systemic administration of OVs is limited because of undesired inactivation caused by host immune system and neutralizing antibodies in the bloodstream. To address this issue, a novel hyaluronic acid based redox responsive nanohydrogel was developed in this study as delivery system for OVs, with the aim to protect the OVs following systemic administration. The nanohydrogel was formulated by water in oil (W/O) nanoemulsion method and cross-linked by disulfide bonds derived from the thiol groups of synthesized thiolated hyaluronic acid. One DNA OV Ad[I/PPT-E1A] and one RNA OV Rigvir^® ECHO-7 were encapsulated into the developed nanohydrogel, respectively, in view of their potential of immunovirotherapy to treat cancers. The nanohydrogels showed particle size of approximately 300–400 nm and negative zeta potential of around −13 mV by dynamic light scattering (DLS). A uniform spherical shape of the nanohydrogel was observed under the scanning electron microscope (SEM) and transmission electron microscope (TEM), especially, the successfully loading of OV into nanohydrogel was revealed by TEM. The crosslinking between the hyaluronic acid chains was confirmed by the appearance of new peak assigned to disulfide bond in Raman spectrum. Furthermore, the redox responsive ability of the nanohydrogel was determined by incubating the nanohydrogel into phosphate buffered saline (PBS) pH 7.4 with 10 μM or 10 mM glutathione at 37 °C which stimulate the normal physiological environment (extracellular) or reductive environment (intracellular or tumoral). The relative turbidity of the sample was real time monitored by DLS which indicated that the nanohydrogel could rapidly degrade within 10 h in the reductive environment due to the cleavage of disulfide bonds, while maintaining the stability in the normal physiological environment after 5 days. Additionally, in vitro cytotoxicity assays demonstrated a good oncolytic activity of OVs-loaded nanohydrogel against the specific cancer cell lines. Overall, the results indicated that the developed nanohydrogel is a delivery system appropriate for viral drugs, due to its hydrophilic and porous nature, and also thanks to its capacity to maintain the stability and activity of encapsulated viruses. Thus, nanohydrogel can be considered as a promising candidate carrier for systemic administration of oncolytic immunovirotherapy. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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9 pages, 971 KiB

Open AccessArticle

Liposome-Mediated Inhibition of Inflammation by Hydroxycitrate

by Antonio Vassallo, Valentina Santoro, Ilaria Pappalardo, Anna Santarsiero, Paolo Convertini, Maria De Luca, Giuseppe Martelli, Vittoria Infantino and Carla Caddeo

Nanomaterials 2020, 10(10), 2080; https://doi.org/10.3390/nano10102080 - 21 Oct 2020

Cited by 17 | Viewed by 2988

Abstract

Hydroxycitrate (HCA), a main organic acid component of the fruit rind of Garcinia cambogia, is a natural citrate analog that can inhibit the ATP citrate lyase (ACLY) enzyme with a consequent reduction of inflammatory mediators (i.e., nitric oxide (NO), reactive oxygen species (ROS), and prostaglandin E₂ (PGE₂)) levels. Therefore, HCA has been proposed as a novel means to prevent, treat, and ameliorate conditions involving inflammation. However, HCA presents a low membrane permeability, and a large quantity is required to have a biological effect. To overcome this problem, HCA was formulated in liposomes in this work, and the enhancement of HCA cell availability along with the reduction in the amount required to downregulate NO, ROS, and PGE₂ in macrophages were assessed. The liposomes were small in size (~60 nm), monodispersed, negatively charged (−50 mV), and stable on storage. The in vitro results showed that the liposomal encapsulation increased by approximately 4 times the intracellular accumulation of HCA in macrophages, and reduced by 10 times the amount of HCA required to abolish LPS-induced NO, ROS, and PGE₂ increase. This suggests that liposomal HCA can be exploited to target the citrate pathway involved in inflammatory processes. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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18 pages, 2920 KiB

Open AccessArticle

Ferulic Acid-NLC with Lavandula Essential Oil: A Possible Strategy for Wound-Healing?

by Claudia Carbone, Carla Caddeo, Maria Aurora Grimaudo, Daniela Erminia Manno, Antonio Serra and Teresa Musumeci

Nanomaterials 2020, 10(5), 898; https://doi.org/10.3390/nano10050898 - 08 May 2020

Cited by 30 | Viewed by 3473

Abstract

Nowadays, an increasing interest in combinatorial drug delivery systems is emerging, highlighting the possibility of exploiting essential oils (EO) for topical applications. This work aimed at developing nanostructured lipid carriers (NLC) for the combined delivery of ferulic acid and Lavandula EO, whose beneficial effects in wound-healing processes have been widely reported. Homogeneous (polydispersity index, PDI < 0.2) nanoparticles with a small size (<150 nm) and a high encapsulation efficiency (>85%) were obtained. The co-presence of ferulic acid and Lavandula EO, as compared to synthetic isopropyl myristate-based NLC, increased nanoparticles’ stability, due to higher ordering chains, as confirmed by morphological and physicochemical studies. An enhanced cytocompatibility was observed when combining ferulic acid and Lavandula EO, as confirmed by in vitro studies on fibroblasts. Furthermore, the combined delivery of ferulic acid and Lavandula EO significantly promoted cell migration with higher effectiveness in respect to the free drug solution and the carrier without the EO. Taken all together, our results suggest a potential combined effect of the antioxidant ferulic acid and Lavandula EO co-delivered in lipid nanoparticles in promoting cell proliferation and migration, representing a promising strategy in the treatment of wounds. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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11 pages, 1784 KiB

Open AccessArticle

Ocular Formulation Based on Palmitoylethanolamide-Loaded Nanostructured Lipid Carriers: Technological and Pharmacological Profile

by Carmelo Puglia, Debora Santonocito, Carmine Ostacolo, Eduardo Maria Sommella, Pietro Campiglia, Claudia Carbone, Filippo Drago, Rosario Pignatello and Claudio Bucolo

Nanomaterials 2020, 10(2), 287; https://doi.org/10.3390/nano10020287 - 08 Feb 2020

Cited by 35 | Viewed by 3245

Abstract

The present work was aimed for the preparation of a stable nanostructured lipid carrier (NLC) system for the delivery of N-palmitoylethanolamide (PEA) to the back of the eye. PEA is an interesting natural compound showing anti-inflammatory and neuroprotective activities. The limits of PEA (poor solubility and high instability) justify its nanoencapsulation into drug delivery systems. Two different well-known techniques were compared to formulate NLC: the high shear homogenization technique (HSH) and the method based on a combination of HSH technique and ultrasonication (HSH/US). Nanoparticles were evaluated in relation to mean size, homogeneity, surface charge, and physical stability by Turbiscan technology. Retinal distribution of PEA was carried out in a rat eye after single instillation of PEA-NLC ophthalmic formulation. The novel formulation delivered remarkable levels of PEA to the retina. Lastly, topical administration of PEA-NLC ophthalmic formulation was able to significantly inhibits retinal tumor necrosis factor-α (TNF-α) levels in streptozotocin-induced diabetic rats. The present findings suggest that the novel ophthalmic formulation may be useful for the treatment of retinal diseases such as diabetic retinopathy. Clinical studies are in progress to evaluate this possibility. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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Review

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36 pages, 1972 KiB

Open AccessReview

Polymeric Nanocapsules as Nanotechnological Alternative for Drug Delivery System: Current Status, Challenges and Opportunities

by Siyuan Deng, Maria Rosa Gigliobianco, Roberta Censi and Piera Di Martino

Nanomaterials 2020, 10(5), 847; https://doi.org/10.3390/nano10050847 - 28 Apr 2020

Cited by 160 | Viewed by 10817

Abstract

Polymer-based nanocapsules have been widely studied as a potential drug delivery system in recent years. Nanocapsules—as one of kind nanoparticle—provide a unique nanostructure, consisting of a liquid/solid core with a polymeric shell. This is of increasing interest in drug delivery applications. In this review, nanocapsules delivery systems studied in last decade are reviewed, along with nanocapsule formulation, characterizations of physical/chemical/biologic properties and applications. Furthermore, the challenges and opportunities of nanocapsules applications are also proposed. Full article

(This article belongs to the Special Issue Nanoencapsulation Strategies for Active Compounds Delivery)

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