Editorial

3 pages, 165 KiB

Open AccessEditorial

Smart Nanovesicles for Drug Targeting and Delivery

by Carlotta Marianecci and Maria Carafa

Pharmaceutics 2019, 11(4), 147; https://doi.org/10.3390/pharmaceutics11040147 - 29 Mar 2019

Cited by 11 | Viewed by 2928

Nanovesicles are highly-promising and versatile systems for the delivery and/or targeting of drugs, biomolecules and contrast agents [...] Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

Research

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12 pages, 2434 KiB

Open AccessArticle

Long-Lasting, Antinociceptive Effects of pH-Sensitive Niosomes Loaded with Ibuprofen in Acute and Chronic Models of Pain

by Francesca Marzoli, Carlotta Marianecci, Federica Rinaldi, Daniele Passeri, Marco Rossi, Paola Minosi, Maria Carafa and Stefano Pieretti

Pharmaceutics 2019, 11(2), 62; https://doi.org/10.3390/pharmaceutics11020062 - 01 Feb 2019

Cited by 15 | Viewed by 3351

Abstract

Ibuprofen is one of the non-steroidal anti-inflammatory drugs (NSAIDs) widely used to treat pain conditions. NSAIDs encounter several obstacles to passing across biological membranes. To overcome these constraints, we decided to study the effects of a new pH-sensitive formulation of niosomes containing Polysorbate [...] Read more.

Ibuprofen is one of the non-steroidal anti-inflammatory drugs (NSAIDs) widely used to treat pain conditions. NSAIDs encounter several obstacles to passing across biological membranes. To overcome these constraints, we decided to study the effects of a new pH-sensitive formulation of niosomes containing Polysorbate 20 derivatized by Glycine and loaded with ibuprofen (NioIbu) in several animal models of pain in mice. We performed two tests commonly used to study acute antinociceptive activity, namely the writhing test and the capsaicin test. Our results demonstrated that NioIbu, administered 2 h before testing, reduced nociception, whereas the free form of ibuprofen was ineffective. In a model of inflammatory pain, hyperalgesia induced by zymosan, NioIbu induced a long-lasting reduction in hyperalgesia in treated mice. In a model of neuropathic pain induced by sciatic nerve chronic constriction, NioIbu reduced both neuropathy-induced allodynia and hyperalgesia. The results obtained in our experiments suggest that pH-sensitive niosomes containing Polysorbate 20 derivatized by Glycine is an effective model for NSAIDs delivery, providing durable antinociceptive effects and reducing the incidence of side effects. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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13 pages, 4120 KiB

Open AccessArticle

In Vitro Anticancer Activity of Extracellular Vesicles (EVs) Secreted by Gingival Mesenchymal Stromal Cells Primed with Paclitaxel

by Valentina Coccè, Silvia Franzè, Anna Teresa Brini, Aldo Bruno Giannì, Luisa Pascucci, Emilio Ciusani, Giulio Alessandri, Giampietro Farronato, Loredana Cavicchini, Valeria Sordi, Rita Paroni, Michele Dei Cas, Francesco Cilurzo and Augusto Pessina

Pharmaceutics 2019, 11(2), 61; https://doi.org/10.3390/pharmaceutics11020061 - 01 Feb 2019

Cited by 45 | Viewed by 4137

Abstract

Interdental papilla are an interesting source of mesenchymal stromal cells (GinPaMSCs), which are easy to isolate and expand in vitro. In our laboratory, GinPaMSCs were isolated, expanded, and characterized by studying their secretome before and after priming with paclitaxel (PTX). The secretome of [...] Read more.

Interdental papilla are an interesting source of mesenchymal stromal cells (GinPaMSCs), which are easy to isolate and expand in vitro. In our laboratory, GinPaMSCs were isolated, expanded, and characterized by studying their secretome before and after priming with paclitaxel (PTX). The secretome of GinPaMSCs did not affect the growth of cancer cell lines tested in vitro, whereas the secretome of GinPaMSCs primed with paclitaxel (GinPaMSCs/PTX) exerted a significant anticancer effect. GinPaMSCs were able to uptake and then release paclitaxel in amounts pharmacologically effective against cancer cells, as demonstrated in vitro by the direct activity of GinPaMSCs/PTX and their secretome against both human pancreatic carcinoma and squamous carcinoma cells. PTX was associated with extracellular vesicles (EVs) secreted by cells (EVs/PTX), suggesting that PTX is incorporated into exosomes during their biogenesis. The isolation of mesenchymal stromal cells (MSCs) from gingiva is less invasive than that from other tissues (such as bone marrow and fat), and GinPaMSCs provide an optimal substrate for drug-priming to obtain EVs/PTX having anticancer activity. This research may contribute to develop new strategies of cell-mediated drug delivery by EVs that are easy to store without losing function, and could have a superior safety profile in therapy. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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15 pages, 3779 KiB

Open AccessArticle

Stable, Monodisperse, and Highly Cell-Permeating Nanocochleates from Natural Soy Lecithin Liposomes

by Martina Asprea, Francesca Tatini, Vieri Piazzini, Francesca Rossi, Maria Camilla Bergonzi and Anna Rita Bilia

Pharmaceutics 2019, 11(1), 34; https://doi.org/10.3390/pharmaceutics11010034 - 16 Jan 2019

Cited by 36 | Viewed by 5320

Abstract

(1) Background: Andrographolide (AN), the main diterpenoid constituent of Andrographis paniculata, has a wide spectrum of biological activities. The aim of this study was the development of nanocochleates (NCs) loaded with AN and based on phosphatidylserine (PS) or phosphatidylcholine (PC), cholesterol and [...] Read more.

(1) Background: Andrographolide (AN), the main diterpenoid constituent of Andrographis paniculata, has a wide spectrum of biological activities. The aim of this study was the development of nanocochleates (NCs) loaded with AN and based on phosphatidylserine (PS) or phosphatidylcholine (PC), cholesterol and calcium ions in order to overcome AN low water solubility, its instability under alkaline conditions and its rapid metabolism in the intestine. (2) Methods: The AN-loaded NCs (AN–NCs) were physically and chemically characterised. The in vitro gastrointestinal stability and biocompatibility of AN–NCs in J77A.1 macrophage and 3T3 fibroblasts cell lines were also investigated. Finally, the uptake of nanocarriers in macrophage cells was studied. (3) Results: AN–NCs obtained from PC nanoliposomes were suitable nanocarriers in terms of size and homogeneity. They had an extraordinary stability after lyophilisation without the use of lyoprotectants and after storage at room temperature. The encapsulation efficiency was 71%, while approximately 95% of AN was released in PBS after 24 h, with kinetics according to the Hixson–Crowell model. The in vitro gastrointestinal stability and safety of NCs, both in macrophages and 3T3 fibroblasts, were also assessed. Additionally, NCs had extraordinary uptake properties in macrophages. (4) Conclusions: NCs developed in this study could be suitable for both AN oral and parental administration, amplifying its therapeutic value. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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12 pages, 4071 KiB

Open AccessArticle

Protein Corona Fingerprints of Liposomes: New Opportunities for Targeted Drug Delivery and Early Detection in Pancreatic Cancer

by Sara Palchetti, Damiano Caputo, Luca Digiacomo, Anna Laura Capriotti, Roberto Coppola, Daniela Pozzi and Giulio Caracciolo

Pharmaceutics 2019, 11(1), 31; https://doi.org/10.3390/pharmaceutics11010031 - 15 Jan 2019

Cited by 40 | Viewed by 5551

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related mortality in the Western world and is envisaged to become the second cause by 2030. Although our knowledge about the molecular biology of PDAC is continuously increasing, this progress has not been translated [...] Read more.

Pancreatic ductal adenocarcinoma (PDAC) is the fourth cause of cancer-related mortality in the Western world and is envisaged to become the second cause by 2030. Although our knowledge about the molecular biology of PDAC is continuously increasing, this progress has not been translated into better patients’ outcome. Liposomes have been used to circumvent concerns associated with the low efficiency of anticancer drugs such as severe side effects and damage of healthy tissues, but they have not resulted in improved efficacy as yet. Recently, the concept is emerging that the limited success of liposomal drugs in clinical practice is due to our poor knowledge of the nano–bio interactions experienced by liposomes in vivo. After systemic administration, lipid vesicles are covered by plasma proteins forming a biomolecular coating, referred to as the protein corona (PC). Recent studies have clarified that just a minor fraction of the hundreds of bound plasma proteins, referred to as “PC fingerprints” (PCFs), enhance liposome association with cancer cells, triggering efficient particle internalization. In this study, we synthesized a library of 10 liposomal formulations with systematic changes in lipid composition and exposed them to human plasma (HP). Size, zeta-potential, and corona composition of the resulting liposome–protein complexes were thoroughly characterized by dynamic light scattering (DLS), micro-electrophoresis, and nano-liquid chromatography tandem mass spectrometry (nano-LC MS/MS). According to the recent literature, enrichment in PCFs was used to predict the targeting ability of synthesized liposomal formulations. Here we show that the predicted targeting capability of liposome–protein complexes clearly correlate with cellular uptake in pancreatic adenocarcinoma (PANC-1) and insulinoma (INS-1) cells as quantified by flow-assisted cell sorting (FACS). Of note, cellular uptake of the liposomal formulation with the highest abundance of PCFs was much larger than that of Onivyde^®, an Irinotecan liposomal drug approved by the Food and Drug Administration in 2015 for the treatment of metastatic PDAC. Given the urgent need of efficient nanocarriers for the treatment of PDAC, we envision that our results will pave the way for the development of more efficient PC-based targeted nanomaterials. Here we also show that some BCs are enriched with plasma proteins that are associated with the onset and progression of PDAC (e.g., sex hormone-binding globulin, Ficolin-3, plasma protease C1 inhibitor, etc.). This could open the intriguing possibility to identify novel biomarkers. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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19 pages, 4214 KiB

Open AccessArticle

Development of Multifunctional Liposomes Containing Magnetic/Plasmonic MnFe₂O₄/Au Core/Shell Nanoparticles

by Ana Rita O. Rodrigues, Joana O. G. Matos, Armando M. Nova Dias, Bernardo G. Almeida, Ana Pires, André M. Pereira, João P. Araújo, Maria-João R. P. Queiroz, Elisabete M. S. Castanheira and Paulo J. G. Coutinho

Pharmaceutics 2019, 11(1), 10; https://doi.org/10.3390/pharmaceutics11010010 - 31 Dec 2018

Cited by 27 | Viewed by 5006

Abstract

Multifunctional liposomes containing manganese ferrite/gold core/shell nanoparticles were developed. These magnetic/plasmonic nanoparticles were covered by a lipid bilayer or entrapped in liposomes, which form solid or aqueous magnetoliposomes as nanocarriers for simultaneous chemotherapy and phototherapy. The core/shell nanoparticles were characterized by UV/Visible absorption, [...] Read more.

Multifunctional liposomes containing manganese ferrite/gold core/shell nanoparticles were developed. These magnetic/plasmonic nanoparticles were covered by a lipid bilayer or entrapped in liposomes, which form solid or aqueous magnetoliposomes as nanocarriers for simultaneous chemotherapy and phototherapy. The core/shell nanoparticles were characterized by UV/Visible absorption, X-Ray Diffraction (XRD), Transmission Electron Microscopy (TEM), and Superconducting Quantum Interference Device (SQUID). The magnetoliposomes were characterized by Dynamic Light Scattering (DLS) and TEM. Fluorescence-based techniques (FRET, steady-state emission, and anisotropy) investigated the incorporation of a potential anti-tumor drug (a thienopyridine derivative) in these nanosystems. The core/shell nanoparticles exhibit sizes of 25 ± 2 nm (from TEM), a plasmonic absorption band (λ_max = 550 nm), and keep magnetic character. XRD measurements allowed for the estimation of 13.3 nm diameter for manganese ferrite core and 11.7 nm due to the gold shell. Aqueous magnetoliposomes, with hydrodynamic diameters of 152 ± 18 nm, interact with model membranes by fusion and are able to transport the anti-tumor compound in the lipid membrane, with a high encapsulation efficiency (EE (%) = 98.4 ± 0.8). Solid magnetoliposomes exhibit hydrodynamic diameters around 140 nm and also carry successfully the anticancer drug (with EE (%) = 91.2 ± 5.2), while also being promising as agents for phototherapy. The developed multifunctional liposomes can be promising as therapeutic agents for combined chemo/phototherapy. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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17 pages, 2216 KiB

Open AccessArticle

SPC Liposomes as Possible Delivery Systems for Improving Bioavailability of the Natural Sesquiterpene β-Caryophyllene: Lamellarity and Drug-Loading as Key Features for a Rational Drug Delivery Design

by Antonella Di Sotto, Patrizia Paolicelli, Martina Nardoni, Lorena Abete, Stefania Garzoli, Silvia Di Giacomo, Gabriela Mazzanti, Maria Antonietta Casadei and Stefania Petralito

Pharmaceutics 2018, 10(4), 274; https://doi.org/10.3390/pharmaceutics10040274 - 13 Dec 2018

Cited by 33 | Viewed by 3645

Abstract

The natural sesquiterpene β-caryophyllene (CRY) has been highlighted to possess interesting pharmacological potentials, particularly due to its chemopreventive and analgesic properties. However, the poor solubility of this sesquiterpene in aqueous fluids can hinder its uptake into cells, resulting in inconstant responses of biological [...] Read more.

The natural sesquiterpene β-caryophyllene (CRY) has been highlighted to possess interesting pharmacological potentials, particularly due to its chemopreventive and analgesic properties. However, the poor solubility of this sesquiterpene in aqueous fluids can hinder its uptake into cells, resulting in inconstant responses of biological systems, thus limiting its application. Therefore, identifying a suitable pharmaceutical form for increasing CRY bioavailability represents an important requirement for exploiting its pharmacological potential. In the present study, the ability of soybean phosphatidylcholine (SPC) liposomes to improve bioavailability and absorption of CRY in cancer cells has been evaluated. Liposomal formulations of CRY, differing for lamellarity (i.e., unilamellar and multilamellar vesicles or ULV and MLV) and for the drug loading (i.e., 1:0.1, 1:0.3 and 1:0.5 mol/mol between SPC and CRY) were designed with the aim of maximizing CRY amount in the liposome bilayer, while avoiding its leakage during storage. The low-loaded formulations significantly potentiated the antiproliferative activity of CRY in both HepG2 and MDA-MB-468 cells, reaching a maximum IC₅₀ lowering (from two to five folds) with 1:0.3 and 1:0.1 SPC/CRY MLV. Conversely, increasing liposome drug-loading reduced the ability for CRY release, likely due to a possible interaction between SPC and CRY that affects the membrane properties, as confirmed by physical measures. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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15 pages, 3686 KiB

Open AccessArticle

Development of Parvifloron D-Loaded Smart Nanoparticles to Target Pancreatic Cancer

by Ana Santos-Rebelo, Catarina Garcia, Carla Eleutério, Ana Bastos, Sílvia Castro Coelho, Manuel A. N. Coelho, Jesús Molpeceres, Ana S. Viana, Lia Ascensão, João F. Pinto, Maria M. Gaspar, Patrícia Rijo and Catarina P. Reis

Pharmaceutics 2018, 10(4), 216; https://doi.org/10.3390/pharmaceutics10040216 - 04 Nov 2018

Cited by 24 | Viewed by 4165

Abstract

Pancreatic cancer is the eighth leading cause of cancer death worldwide. For this reason, the development of more effective therapies is a major concern for the scientific community. Accordingly, plants belonging to Plectranthus genus and their isolated compounds, such as Parvifloron D, were [...] Read more.

Pancreatic cancer is the eighth leading cause of cancer death worldwide. For this reason, the development of more effective therapies is a major concern for the scientific community. Accordingly, plants belonging to Plectranthus genus and their isolated compounds, such as Parvifloron D, were found to have cytotoxic and antiproliferative activities. However, Parvifloron D is a very low water-soluble compound. Thus, nanotechnology can be a promising delivery system to enhance drug solubility and targeted delivery. The extraction of Parvifloron D from P. ecklonii was optimized through an acetone ultrasound-assisted method and isolated by Flash-Dry Column Chromatography. Then, its antiproliferative effect was selectivity evaluated against different cell lines (IC₅₀ of 0.15 ± 0.05 μM, 11.9 ± 0.7 μM, 21.6 ± 0.5, 34.3 ± 4.1 μM, 35.1 ± 2.2 μM and 32.1 ± 4.3 μM for BxPC3, PANC-1, Ins1-E, MCF-7, HaCat and Caco-2, respectively). To obtain an optimized stable Parvifloron D pharmaceutical dosage form, albumin nanoparticles were produced through a desolvation method (yield of encapsulation of 91.2%) and characterized in terms of size (165 nm; PI 0.11), zeta potential (−7.88 mV) and morphology. In conclusion, Parvifloron D can be efficiently obtained from P. ecklonii and it has shown selective cytotoxicity to pancreatic cell lines. Parvifloron D nanoencapsulation can be considered as a possible efficient alternative approach in the treatment of pancreatic cancer. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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19 pages, 2265 KiB

Open AccessArticle

Stealth and Cationic Nanoliposomes as Drug Delivery Systems to Increase Andrographolide BBB Permeability

by Vieri Piazzini, Elisa Landucci, Giulia Graverini, Domenico E. Pellegrini-Giampietro, Anna Rita Bilia and Maria Camilla Bergonzi

Pharmaceutics 2018, 10(3), 128; https://doi.org/10.3390/pharmaceutics10030128 - 13 Aug 2018

Cited by 55 | Viewed by 4844

Abstract

(1) Background: Andrographolide (AG) is a natural compound effective for the treatment of inflammation-mediated neurodegenerative disorders. The aim of this investigation was the preparation of liposomes to enhance the penetration into the brain of AG, by modifying the surface of the liposomes by [...] Read more.

(1) Background: Andrographolide (AG) is a natural compound effective for the treatment of inflammation-mediated neurodegenerative disorders. The aim of this investigation was the preparation of liposomes to enhance the penetration into the brain of AG, by modifying the surface of the liposomes by adding Tween 80 (LPs-AG) alone or in combination with Didecyldimethylammonium bromide (DDAB) (CLPs-AG). (2) Methods: LPs-AG and CLPs-AG were physically and chemically characterized. The ability of liposomes to increase the permeability of AG was evaluated by artificial membranes (PAMPA) and hCMEC/D3 cells. (3) Results: Based on obtained results in terms of size, homogeneity, ζ-potential and EE%. both liposomes are suitable for parenteral administration. The systems showed excellent stability during a month of storage as suspensions or freeze-dried products. Glucose resulted the best cryoprotectant agent. PAMPA and hCMEC/D3 transport studies revealed that LPs-AG and CLPs-AG increased the permeability of AG, about an order of magnitude, compared to free AG without alterations in cell viability. The caveolae-mediated endocytosis resulted the main mechanism of up-take for both formulations. The presence of positive charge increased the cellular internalization of nanoparticles. (4) Conclusions: This study shows that developed liposomes might be ideal candidates for brain delivery of AG. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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13 pages, 1955 KiB

Open AccessArticle

Buspirone Nanovesicular Nasal System for Non-Hormonal Hot Flushes Treatment

by Elka Touitou, Hiba Natsheh and Shaher Duchi

Pharmaceutics 2018, 10(3), 82; https://doi.org/10.3390/pharmaceutics10030082 - 03 Jul 2018

Cited by 9 | Viewed by 4974

Abstract

The aim of this work was to design and characterize a new nanovesicular nasal delivery system (NDS) containing buspirone, and investigate its efficiency in an animal model for the treatment of hot flushes. The presence of multilamellar vesicles with a mean size distribution [...] Read more.

The aim of this work was to design and characterize a new nanovesicular nasal delivery system (NDS) containing buspirone, and investigate its efficiency in an animal model for the treatment of hot flushes. The presence of multilamellar vesicles with a mean size distribution of 370 nm was evidenced by transition electron microscopy (TEM), cryo-scanning electron microscopy (Cryo-SEM), and dynamic light scattering (DLS) tests. Pharmacodynamic evaluation of the nasal treatment efficacy with the new system was carried out in ovariectomized (OVX) rat—an animal model for hot flushes—and compared with other treatments. We found that the nasal administration of a buspirone NDS resulted in a significant reduction in tail skin temperature (TST). This effect was not observed in the control buspirone-treated groups. Buspirone levels in the plasma and brain of nasally-treated normal rats were quantified and compared with those of rats that had received oral administration by a LC-MS/MS assay. A significantly higher bioavailability was achieved with the new treatment relative to an oral administration of the same drug dose. No pathological changes in the nasal cavity were observed following sub-chronic nasal administration of buspirone NDS. In conclusion, the data of our investigation show that buspirone in the new nanovesicular nasal carrier could be considered for further studies for the development of a treatment for the hot flushes ailment. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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Review

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49 pages, 3702 KiB

Open AccessReview

Mesoporous Silica Nanoparticles: A Comprehensive Review on Synthesis and Recent Advances

by Reema Narayan, Usha Y. Nayak, Ashok M. Raichur and Sanjay Garg

Pharmaceutics 2018, 10(3), 118; https://doi.org/10.3390/pharmaceutics10030118 - 06 Aug 2018

Cited by 572 | Viewed by 26665

Abstract

Recent advancements in drug delivery technologies utilizing a variety of carriers have resulted in a path-breaking revolution in the approach towards diagnosis and therapy alike in the current times. Need for materials with high thermal, chemical and mechanical properties have led to the [...] Read more.

Recent advancements in drug delivery technologies utilizing a variety of carriers have resulted in a path-breaking revolution in the approach towards diagnosis and therapy alike in the current times. Need for materials with high thermal, chemical and mechanical properties have led to the development of mesoporous silica nanoparticles (MSNs). These ordered porous materials have garnered immense attention as drug carriers owing to their distinctive features over the others. They can be synthesized using a relatively simple process, thus making it cost effective. Moreover, by controlling the parameters during the synthesis; the morphology, pore size and volume and particle size can be transformed accordingly. Over the last few years, a rapid increase in research on MSNs as drug carriers for the treatment of various diseases has been observed indicating its potential benefits in drug delivery. Their widespread application for the loading of small molecules as well as macromolecules such as proteins, siRNA and so forth, has made it a versatile carrier. In the recent times, researchers have sorted to several modifications in the framework of MSNs to explore its potential in drug resistant chemotherapy, antimicrobial therapy. In this review, we have discussed the synthesis of these multitalented nanoparticles and the factors influencing the size and morphology of this wonder carrier. The second part of this review emphasizes on the applications and the advances made in the MSNs to broaden the spectrum of its use especially in the field of biomedicine. We have also touched upon the lacunae in the thorough understanding of its interaction with a biological system which poses a major hurdle in the passage of this carrier to the clinical level. In the final part of this review, we have discussed some of the major patents filed in the field of MSNs for therapeutic purpose. Full article

(This article belongs to the Special Issue Smart Nanovesicles for Drug Targeting and Delivery)

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