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Nanosystems in Pharmaceutical Technology
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Nanosystems in Pharmaceutical Technology

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Nanochemistry".

Deadline for manuscript submissions: closed (31 July 2021) | Viewed by 36226

Special Issue Editors

Prof. Dr. Valentina Venuti

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Guest Editor
Università degli Studi di Messina, Messina, Italy
Interests: drug delivery systems; polymeric materials; FTIR-ATR spectroscopy; Raman spectroscopy; neutron techniques; materials characterization
Prof. Dr. Rosanna Stancanelli

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Guest Editor
Università degli Studi di Messina, Messina, Italy
Interests: cyclodextrins; inclusion complex; pharmaceutical development; nanotechnology in drug delivery
Prof. Dr. Silvana Tommasini

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Guest Editor
Università degli Studi di Messina, Messina, Italy
Interests: cyclodextrins; inclusion complex; pharmaceutical development; nanotechnology in drug delivery
Prof. Dr. Cinzia Anna Ventura

E-Mail Website
Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
Interests: drug delivery; drug/cyclodextrin inclusion complexes; polymeric nanoparticles; cancer diseases; antimicrobial drugs; Alzheimer’s disease
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Vincenza Crupi

E-Mail Website
Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy
Interests: drug delivery systems; polymeric materials; FTIR-ATR spectroscopy; Raman spectroscopy; neutron techniques; materials characterization
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Domenico Majolino

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Guest Editor
Università degli Studi di Messina, Messina, Italy
Interests: drug delivery systems; polymeric materials; FTIR-ATR spectroscopy; Raman spectroscopy; neutron techniques; materials characterization

Special Issue Information

Dear Colleagues,

The development of new therapeutic products is not very often adequate to properly enhance those properties that usually limit their biological applications, such as water solubility, circulation time, and pharmacokinetic profile. Furthermore, new potentially therapeutic molecules fail to permeate the cell membrane, thus requiring a high dose to obtain a good bioavailability with consequent toxicity and undesired side effects. In this scenario, nanotechnology, through the employment of materials in the nanoscale range, is currently being developed and looks particularly promising in revolutionizing targeted drug delivery, gene therapy, diagnostics, and many related areas of research.

The aim of this Special Issue is to go deep inside the challenges in “Nanosystems in Pharmaceutical Technology”, presenting recent innovations in nanomaterials for biomedical applications. As Guest Editors, we cordially invite you to contribute a research paper or comprehensive review on any aspect related to this topic.

Prof. Dr. Valentina Venuti
Prof. Dr. Rosanna Stancanelli
Prof. Dr. Silvana Tommasini
Prof. Dr. Cinzia Anna Ventura
Prof. Dr. Vincenza Crupi
Prof. Dr. Domenico Majolino
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. Molecules 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 2700 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

  • Nanopharmaceuticals
  • Nanodiagnostics
  • Nanotherapeutics
  • Nanosized targeted drug delivery
  • Biomedical applications
  • Nanomedicine

Published Papers (9 papers)

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Research

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17 pages, 2548 KiB  
Article
Development of New Targeted Inulin Complex Nanoaggregates for siRNA Delivery in Antitumor Therapy
by Gennara Cavallaro, Carla Sardo, Emanuela Fabiola Craparo and Gaetano Giammona
Molecules 2021, 26(6), 1713; https://doi.org/10.3390/molecules26061713 - 19 Mar 2021
Cited by 6 | Viewed by 1755
Abstract
Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized [...] Read more.
Here, a novel strategy of formulating efficient polymeric carriers based on the already described INU-IMI-DETA for gene material whose structural, functional, and biological properties can be modulated and improved was successfully investigated. In particular, two novel derivatives of INU-IMI-DETA graft copolymer were synthesized by chemical functionalisation with epidermal growth factor (EGF) or polyethylenglycol (PEG), named INU-IMI-DETA-EGF and INU-IMI-DETA-PEG, respectively, in order to improve the performance of already described “inulin complex nanoaggregates” (ICONs). The latter were thus prepared by appropriately mixing the two copolymers, by varying each component from 0 to 100 wt% on the total mixture, named EP-ICONs. It was seen that the ability of the INU-IMI-DETA-EGF/INU-IMI-DETA-PEG polymeric mixture to complex siGL3 increases with the increase in the EGF-based component in the EP-ICONs and, for each sample, with the increase in the copolymer:siRNA weight ratio (R). On the other hand, the susceptibility of loaded siRNA towards RNase decreases with the increase in the pegylated component in the polymeric mixture. At all R values, the average size and the zeta potential values are suitable for escaping from the RES system and suitable for prolonged intravenous circulation. By means of biological characterisation, it was shown that MCF-7 cells are able to internalize mainly the siRNA-loaded into EGF-decorated complexes, with a significant difference from ICONs, confirming its targeting function. The targeting effect of EGF on EP-ICONs was further demonstrated by a competitive cell uptake study, i.e., after cell pre-treatment with EGF. Finally, it was shown that the complexes containing both EGF and PEG are capable of promoting the internalisation and therefore the transfection of siSUR, a siRNA acting against surviving mRNA, and to increase the sensitivity to an anticancer agent, such as doxorubicin. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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18 pages, 3522 KiB  
Article
Formulation of Cannabidiol in Colloidal Lipid Carriers
by Nadine Monika Francke, Frederic Schneider, Knut Baumann and Heike Bunjes
Molecules 2021, 26(5), 1469; https://doi.org/10.3390/molecules26051469 - 08 Mar 2021
Cited by 21 | Viewed by 4299
Abstract
In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option [...] Read more.
In this study, the general processability of cannabidiol (CBD) in colloidal lipid carriers was investigated. Due to its many pharmacological effects, the pharmaceutical use of this poorly water-soluble drug is currently under intensive research and colloidal lipid emulsions are a well-established formulation option for such lipophilic substances. To obtain a better understanding of the formulability of CBD in lipid emulsions, different aspects of CBD loading and its interaction with the emulsion droplets were investigated. Very high drug loads (>40% related to lipid content) could be achieved in emulsions of medium chain triglycerides, rapeseed oil, soybean oil and trimyristin. The maximum CBD load depended on the type of lipid matrix. CBD loading increased the particle size and the density of the lipid matrix. The loading capacity of a trimyristin emulsion for CBD was superior to that of a suspension of solid lipid nanoparticles based on trimyristin (69% vs. 30% related to the lipid matrix). In addition to its localization within the lipid core of the emulsion droplets, cannabidiol was associated with the droplet interface to a remarkable extent. According to a stress test, CBD destabilized the emulsions, with phospholipid-stabilized emulsions being more stable than poloxamer-stabilized ones. Furthermore, it was possible to produce emulsions with pure CBD as the dispersed phase, since CBD demonstrated such a pronounced supercooling tendency that it did not recrystallize, even if cooled to −60 °C. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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16 pages, 2464 KiB  
Article
Rutin-Loaded Solid Lipid Nanoparticles: Characterization and In Vitro Evaluation
by Federica De Gaetano, Maria Chiara Cristiano, Valentina Venuti, Vincenza Crupi, Domenico Majolino, Giuseppe Paladini, Giuseppe Acri, Barbara Testagrossa, Alessia Irrera, Donatella Paolino, Silvana Tommasini, Cinzia Anna Ventura and Rosanna Stancanelli
Molecules 2021, 26(4), 1039; https://doi.org/10.3390/molecules26041039 - 16 Feb 2021
Cited by 20 | Viewed by 2820
Abstract
This study was aimed at preparing and characterizing solid lipid nanoparticles loading rutin (RT-SLNs) for the treatment of oxidative stress-induced diseases. Phospholipon 80H® as a solid lipid and Polysorbate 80 as surfactant were used for the SLNs preparation, using the solvent emulsification/diffusion [...] Read more.
This study was aimed at preparing and characterizing solid lipid nanoparticles loading rutin (RT-SLNs) for the treatment of oxidative stress-induced diseases. Phospholipon 80H® as a solid lipid and Polysorbate 80 as surfactant were used for the SLNs preparation, using the solvent emulsification/diffusion method. We obtained spherical RT-SLNs with low sizes, ranging from 40 to 60 nm (hydrodynamic radius) for the SLNs prepared starting from 2% and 5% (w/w) theoretical amount. All prepared formulations showed negative zeta-potential values. RT was efficiently encapsulated within SLNs, obtaining high encapsulation efficiency and drug content percentages, particularly for SLNs prepared with a 5% theoretical amount of RT. In vitro release profiles and analysis of the obtained data applying different kinetic models revealed Fickian diffusion as the main mechanism of RT release from the SLNs. The morphology of RT-SLNs was characterized by scanning electron microscopy (SEM), whereas the interactions between RT and the lipid matrix were investigated by Raman spectroscopy, evidencing spectral modifications of characteristic bands of RT due to the establishment of new interactions. Finally, antioxidant activity assay on human glioblastoma astrocytoma (U373) culture cells showed a dose-dependent activity for RT-SLNs, particularly at the highest assayed dose (50 μM), whereas the free drug showed the lesser activity. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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13 pages, 7534 KiB  
Article
Lyophilized Drug-Loaded Solid Lipid Nanoparticles Formulated with Beeswax and Theobroma Oil
by Hilda Amekyeh and Nashiru Billa
Molecules 2021, 26(4), 908; https://doi.org/10.3390/molecules26040908 - 09 Feb 2021
Cited by 11 | Viewed by 3261
Abstract
Solid lipid nanoparticles (SLNs) have the potential to enhance the systemic availability of an active pharmaceutical ingredient (API) or reduce its toxicity through uptake of the SLNs from the gastrointestinal tract or controlled release of the API, respectively. In both aspects, the responses [...] Read more.
Solid lipid nanoparticles (SLNs) have the potential to enhance the systemic availability of an active pharmaceutical ingredient (API) or reduce its toxicity through uptake of the SLNs from the gastrointestinal tract or controlled release of the API, respectively. In both aspects, the responses of the lipid matrix to external challenges is crucial. Here, we evaluate the effects of lyophilization on key responses of 1:1 beeswax–theobroma oil matrix SLNs using three model drugs: amphotericin B (AMB), paracetamol (PAR), and sulfasalazine (SSZ). Fresh SLNs were stable with sizes ranging between 206.5–236.9 nm. Lyophilization and storage for 24 months (4–8 °C) caused a 1.6- and 1.5-fold increase in size, respectively, in all three SLNs. Zeta potential was >60 mV in fresh, stored, and lyophilized SLNs, indicating good colloidal stability. Drug release was not significantly affected by lyophilization up to 8 h. Drug release percentages at end time were 11.8 ± 0.4, 65.9 ± 0.04, and 31.4 ± 1.95% from fresh AMB-SLNs, PAR-SLNs, and SSZ-SLNs, respectively, and 11.4 ± 0.4, 76.04 ± 0.21, and 31.6 ± 0.33% from lyophilized SLNs, respectively. Thus, rate of release is dependent on API solubility (AMB < SSZ < PAR). Drug release from each matrix followed the Higuchi model and was not affected by lyophilization. The above SLNs show potential for use in delivering hydrophilic and lipophilic drugs. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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11 pages, 1200 KiB  
Communication
An Underestimated Factor: The Extent of Cross-Reactions Modifying APIs in Surface-Modified Liposomal Preparations Caused by Comprised Activated Lipids
by Max Sauter, Jürgen Burhenne, Walter E. Haefeli and Philipp Uhl
Molecules 2020, 25(19), 4436; https://doi.org/10.3390/molecules25194436 - 27 Sep 2020
Cited by 2 | Viewed by 3048
Abstract
Despite the nowadays available plentitude of strategies to selectively introduce functional surface modification of liposomes, in preclinical research this process is still primarily performed after liposomal preparation utilizing comprised activated phospholipids with functionalized head groups. However, because these activated lipids are present during [...] Read more.
Despite the nowadays available plentitude of strategies to selectively introduce functional surface modification of liposomes, in preclinical research this process is still primarily performed after liposomal preparation utilizing comprised activated phospholipids with functionalized head groups. However, because these activated lipids are present during the liposomal preparation process, they can cross-react with incorporated drugs, especially the particularly often utilized active esters and maleimide groups. Macromolecular drugs, being composed of amino acids, are particularly prone to such cross-reactions due to their often multiple reactive functionalities such as amino and disulfide groups. To demonstrate this impact on the formulation in liposomal surface modification, we assessed the extent of cross-reaction during the liposomal preparation of two activated phospholipids with typically used head group functionalized phospholipids, with the two peptide drugs vancomycin and insulin comprising disulfide and amino functionalities. Both drugs revealed a considerable fraction of covalent modification (estimated 2 to 12%) generated during the liposome preparation process with comprised activated lipids. Modification of the active pharmaceutical ingredients (APIs) was determined by high-resolution mass spectrometric analysis. These findings clearly demonstrate the non-negligibility of potential cross reactions using the post preparation liposomal surface modification strategy in preclinical research. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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21 pages, 5037 KiB  
Article
The Rheolaser Master™ and Kinexus Rotational Rheometer® to Evaluate the Influence of Topical Drug Delivery Systems on Rheological Features of Topical Poloxamer Gel
by Maria Chiara Cristiano, Francesca Froiio, Antonia Mancuso, Federica De Gaetano, Cinzia Anna Ventura, Massimo Fresta and Donatella Paolino
Molecules 2020, 25(8), 1979; https://doi.org/10.3390/molecules25081979 - 23 Apr 2020
Cited by 26 | Viewed by 4257
Abstract
Poloxamer 407 copolymer is a versatile and widely used thermo-reversible material. Its use has many advantages, such as bio-adhesion, enhanced solubilization of poorly water-soluble drugs and many applications fields like oral, rectal, topical, nasal drug administration. Hydrogels made up of Poloxamer 407 are [...] Read more.
Poloxamer 407 copolymer is a versatile and widely used thermo-reversible material. Its use has many advantages, such as bio-adhesion, enhanced solubilization of poorly water-soluble drugs and many applications fields like oral, rectal, topical, nasal drug administration. Hydrogels made up of Poloxamer 407 are characterized by specific rheological features, which are affected by temperature, concentration and presence of other compounds. A strategic approach in topical therapeutic treatments may be the inclusion of drug delivery systems, such as ethosomes, transfersomes and niosomes, into hydrogel poloxamer formulation. The evaluation of the interaction between colloidal carriers and the Poloxamer 407 hydrogel network is essential for a suitable design of an innovative topical dosage form. For this reason, the Rheolaser Master™, based on diffusing wave spectroscopy, and a Kinexus Rotational Rheometer were used to evaluate the influence of nanocarriers on the microrheological features of hydrogels. The advantages of the Rheolaser Master™ analyzer are: (i) its ability to determine viscoelastic parameter, without altering or destroying the sample and at rest (zero shear); (ii) possibility of aging analysis on the same sample. This study provide evidence that vesicular systems do not influence the rheological features of the gel, supporting the possibility to encapsulate an innovative system into a three-dimensional network. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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7 pages, 222 KiB  
Article
The Use of Different Commercial Mineral Water Brands to Produce Oil-In-Water Nanoemulsions
by Pedro A Rocha-Filho, Antonio D. Monteiro, Luciana C. Agostinho and Marina P. A. Oliveira
Molecules 2020, 25(3), 603; https://doi.org/10.3390/molecules25030603 - 30 Jan 2020
Cited by 1 | Viewed by 2680
Abstract
Nanoemulsions are submicron-size colloidal systems that have the ability to encapsulate, protect, and deliver active ingredients. They have been used in the pharmaceutical, cosmetics, and food industries to improve the absorption of drugs by the skin or via the gastrointestinal tract, aide in [...] Read more.
Nanoemulsions are submicron-size colloidal systems that have the ability to encapsulate, protect, and deliver active ingredients. They have been used in the pharmaceutical, cosmetics, and food industries to improve the absorption of drugs by the skin or via the gastrointestinal tract, aide in food conservation, and treat skin problems. To proper formulate a nanoemulsion, it is important to know the characteristics of its components (aqueous and oil phases, surfactants and additives), as well as the influence on the production method that will be used. This study investigates the influence of aqueous phase composition, stability and particle size in an oil-and-water nanoemulsion formation. By using a low energy method, the purified water was exchanged for different commercial mineral water and saline solutions, and the results of stability, particle size, pH and conductivity tests, were compared. These results show that the minerals present in commercial waters may alter the particle size, pH and conductivity values of nanoemulsions, as well as their stability. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)

Review

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30 pages, 2538 KiB  
Review
Influence of Materials Properties on Bio-Physical Features and Effectiveness of 3D-Scaffolds for Periodontal Regeneration
by Nicola d’Avanzo, Maria Chiara Bruno, Amerigo Giudice, Antonia Mancuso, Federica De Gaetano, Maria Chiara Cristiano, Donatella Paolino and Massimo Fresta
Molecules 2021, 26(6), 1643; https://doi.org/10.3390/molecules26061643 - 15 Mar 2021
Cited by 21 | Viewed by 3988
Abstract
Periodontal diseases are multifactorial disorders, mainly due to severe infections and inflammation which affect the tissues (i.e., gum and dental bone) that support and surround the teeth. These pathologies are characterized by bleeding gums, pain, bad breath and, in more severe forms, can [...] Read more.
Periodontal diseases are multifactorial disorders, mainly due to severe infections and inflammation which affect the tissues (i.e., gum and dental bone) that support and surround the teeth. These pathologies are characterized by bleeding gums, pain, bad breath and, in more severe forms, can lead to the detachment of gum from teeth, causing their loss. To date it is estimated that severe periodontal diseases affect around 10% of the population worldwide thus making necessary the development of effective treatments able to both reduce the infections and inflammation in injured sites and improve the regeneration of damaged tissues. In this scenario, the use of 3D scaffolds can play a pivotal role by providing an effective platform for drugs, nanosystems, growth factors, stem cells, etc., improving the effectiveness of therapies and reducing their systemic side effects. The aim of this review is to describe the recent progress in periodontal regeneration, highlighting the influence of materials’ properties used to realize three-dimensional (3D)-scaffolds, their bio-physical characteristics and their ability to provide a biocompatible platform able to embed nanosystems. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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29 pages, 2356 KiB  
Review
Chitosan Nanoparticles-Insight into Properties, Functionalization and Applications in Drug Delivery and Theranostics
by Jhanvi Jhaveri, Zarna Raichura, Tabassum Khan, Munira Momin and Abdelwahab Omri
Molecules 2021, 26(2), 272; https://doi.org/10.3390/molecules26020272 - 07 Jan 2021
Cited by 135 | Viewed by 8966
Abstract
Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug [...] Read more.
Nanotechnology-based development of drug delivery systems is an attractive area of research in formulation driven R&D laboratories that makes administration of new and complex drugs feasible. It plays a significant role in the design of novel dosage forms by attributing target specific drug delivery, controlled drug release, improved, patient friendly drug regimen and lower side effects. Polysaccharides, especially chitosan, occupy an important place and are widely used in nano drug delivery systems owing to their biocompatibility and biodegradability. This review focuses on chitosan nanoparticles and envisages to provide an insight into the chemistry, properties, drug release mechanisms, preparation techniques and the vast evolving landscape of diverse applications across disease categories leading to development of better therapeutics and superior clinical outcomes. It summarizes recent advancement in the development and utility of functionalized chitosan in anticancer therapeutics, cancer immunotherapy, theranostics and multistage delivery systems. Full article
(This article belongs to the Special Issue Nanosystems in Pharmaceutical Technology)
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