Research

Jump to: Review

11 pages, 1862 KiB

Open AccessArticle

Sustained Release of Minor-Groove-Binding Antibiotic Netropsin from Calcium-Coated Groove-Rich DNA Particles

by Hyunsu Jeon, Hyangsu Nam and Jong Bum Lee

Pharmaceutics 2019, 11(8), 387; https://doi.org/10.3390/pharmaceutics11080387 - 02 Aug 2019

Cited by 11 | Viewed by 3527

Control of the release properties of drugs has been considered a key factor in the development of drug delivery systems (DDSs). However, drug delivery has limitations including cytotoxicity, low loading efficiency, and burst release. To overcome these challenges, nano or micro-particles have been [...] Read more.

Control of the release properties of drugs has been considered a key factor in the development of drug delivery systems (DDSs). However, drug delivery has limitations including cytotoxicity, low loading efficiency, and burst release. To overcome these challenges, nano or micro-particles have been suggested as carrier systems to deliver chemical drugs. Herein, nano-sized DNA particles (DNAp) were manufactured to deliver netropsin, which is known to bind to DNA minor grooves. The rationally designed particles with exposed rich minor grooves were prepared by DNAp synthesis via rolling circle amplification (RCA). DNAp could load large quantities of netropsin in its minor grooves. An analytical method was also developed for the quantification of netropsin binding to DNAp by UV–visible spectrometry. Moreover, controlled release of netropsin was achieved by forming a layer of Ca²⁺ on the DNAp (CaDNAp). As a proof of concept, the sustained release of netropsin by CaDNAp highlights the potential of the DNAp-based delivery approach. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Graphical abstract

14 pages, 2615 KiB

Open AccessArticle

Everolimus Nanoformulation in Biological Nanoparticles Increases Drug Responsiveness in Resistant and Low-Responsive Breast Cancer Cell Lines

by Arianna Bonizzi, Marta Truffi, Marta Sevieri, Raffaele Allevi, Leopoldo Sitia, Roberta Ottria, Luca Sorrentino, Cristina Sottani, Sara Negri, Elena Grignani, Serena Mazzucchelli and Fabio Corsi

Pharmaceutics 2019, 11(8), 384; https://doi.org/10.3390/pharmaceutics11080384 - 02 Aug 2019

Cited by 18 | Viewed by 3429

Abstract

Everolimus (Eve) is an FDA approved drug that inhibits mammalian target of rapamycin (mTOR). It is employed in breast cancer treatment even if its responsiveness is controversial. In an attempt to increase Eve effectiveness, we have developed a novel Eve nanoformulation exploiting H-ferritin [...] Read more.

Everolimus (Eve) is an FDA approved drug that inhibits mammalian target of rapamycin (mTOR). It is employed in breast cancer treatment even if its responsiveness is controversial. In an attempt to increase Eve effectiveness, we have developed a novel Eve nanoformulation exploiting H-ferritin nanocages (HEve) to improve its subcellular delivery. We took advantage of the natural tumor targeting of H-Ferritin, which is mediated by the transferrin receptor-1 (TfR1). Breast cancer cells overexpressing TfR-1 were successfully recognized by H-Ferritin, displaying quick nanocage internalization. HEve has been tested and compared to Eve for in vitro efficacy in sensitive and resistant breast cancer cells. Nanoformulated Eve induced remarkable antiproliferative activity in vitro, making even resistant cell lines sensitive to Eve. Moreover, the antiproliferative activity of HEve is fully in accordance with cytotoxicity observed by cell death assay. Furthermore, the significant increase in anticancer efficacy displayed in HEve-treated samples is due to the improved drug accumulation, as demonstrated by UHPLC-MS/MS quantifications. Our findings suggest that optimizing Eve subcellular delivery, thanks to nanoformulation, determines its improved antitumor activity in a panel of Eve-sensitive or resistant breast cancer cell lines. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Graphical abstract

18 pages, 4118 KiB

Open AccessArticle

Development of Bioinspired Gelatin and Gelatin/Chitosan Bilayer Hydrofilms for Wound Healing

by Itxaso Garcia-Orue, Edorta Santos-Vizcaino, Alaitz Etxabide, Jone Uranga, Ardeshir Bayat, Pedro Guerrero, Manoli Igartua, Koro de la Caba and Rosa Maria Hernandez

Pharmaceutics 2019, 11(7), 314; https://doi.org/10.3390/pharmaceutics11070314 - 04 Jul 2019

Cited by 41 | Viewed by 4727

Abstract

In the current study, we developed a novel gelatin-based bilayer wound dressing. We used different crosslinking agents to confer unique properties to each layer, obtaining a bioinspired multifunctional hydrofilm suitable for wound healing. First, we produced a resistant and non-degradable upper layer by [...] Read more.

In the current study, we developed a novel gelatin-based bilayer wound dressing. We used different crosslinking agents to confer unique properties to each layer, obtaining a bioinspired multifunctional hydrofilm suitable for wound healing. First, we produced a resistant and non-degradable upper layer by lactose-mediated crosslinking of gelatin, which provided mechanical support and protection to overall design. For the lower layer, we crosslinked gelatin with citric acid, resulting in a porous matrix with a great swelling ability. In addition, we incorporated chitosan into the lower layer to harness its wound healing ability. FTIR and SEM analyses showed that lactose addition changed the secondary structure of gelatin, leading to a more compact and smoother structure than that obtained with citric acid. The hydrofilm was able to swell 384.2 ± 57.2% of its dry weight while maintaining mechanical integrity. Besides, its water vapour transmission rate was in the range of commercial dressings (1381.5 ± 108.6 g/m²·day). In vitro, cytotoxicity assays revealed excellent biocompatibility. Finally, the hydrofilm was analysed through an ex vivo wound healing assay in human skin. It achieved similar results to the control in terms of biocompatibility and wound healing, showing suitable characteristics to be used as a wound dressing. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Graphical abstract

21 pages, 1484 KiB

Open AccessArticle

Phytosomes with Persimmon (Diospyros kaki L.) Extract: Preparation and Preliminary Demonstration of In Vivo Tolerability

by Rosa Direito, Catarina Reis, Luís Roque, Margarida Gonçalves, Ana Sanches-Silva, Maria Manuela Gaspar, Rui Pinto, João Rocha, Bruno Sepodes, Maria Rosário Bronze and Maria Eduardo Figueira

Pharmaceutics 2019, 11(6), 296; https://doi.org/10.3390/pharmaceutics11060296 - 22 Jun 2019

Cited by 29 | Viewed by 4988

Abstract

Persimmon (Diospyros kaki L.), a fruit rich in phenolic compounds (PCs), has been considered effective in mitigating oxidative damage induced by an excess of reactive oxygen species. Due to large molecular weight and intrinsic instability in some physiological fluids, PCs’ passage through [...] Read more.

Persimmon (Diospyros kaki L.), a fruit rich in phenolic compounds (PCs), has been considered effective in mitigating oxidative damage induced by an excess of reactive oxygen species. Due to large molecular weight and intrinsic instability in some physiological fluids, PCs’ passage through biological membranes is very limited. Carriers like phytosomes are promising systems to optimize oral absorption of encapsulated extracts. This work prepared and fully characterized phytosomes containing bioactive phenolic extracts from persimmon in terms of size, surface charge, encapsulation efficiency and stability over six months. These phytosomes were orally dosed to Wistar rats during a 15-day period. Afterwards, haematological and biochemical analyses were performed. Monodisperse phytosomes were successfully prepared, with size less than 300nm (PI < 0.3) and high encapsulation efficiency (97.4%) of PCs. In contrast to free extract, extract-loaded phytosomes had higher antioxidant activity after 6 months storage. Oral administration of extract-loaded phytosomes and free extract did not lead to lipidic profile changes and were within referenced normal ranges, as well as glycaemia levels and urine parameters. The results highlighted the potential of persimmon PCs as food supplements or pharmacological tools, suggesting a promising and safe phytosomal formulation containing bioactive agents of persimmon that could lead to health benefits. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Graphical abstract

14 pages, 2522 KiB

Open AccessArticle

Rotavirus VP6 as an Adjuvant for Bivalent Norovirus Vaccine Produced in Nicotiana benthamiana

by Maria Malm, André Diessner, Kirsi Tamminen, Markus Liebscher, Timo Vesikari and Vesna Blazevic

Pharmaceutics 2019, 11(5), 229; https://doi.org/10.3390/pharmaceutics11050229 - 11 May 2019

Cited by 19 | Viewed by 4313

Abstract

Rotaviruses (RVs) and noroviruses (NoVs) are major causes of childhood acute gastroenteritis. During development of a combination vaccine based on NoV virus-like particles (VLP) and RV VP6 produced in baculovirus expression system in insect cells, a dual role of VP6 as a vaccine [...] Read more.

Rotaviruses (RVs) and noroviruses (NoVs) are major causes of childhood acute gastroenteritis. During development of a combination vaccine based on NoV virus-like particles (VLP) and RV VP6 produced in baculovirus expression system in insect cells, a dual role of VP6 as a vaccine antigen and an adjuvant for NoV-specific immune responses was discovered. Here the VP6 adjuvant effect on bivalent GI.4 and GII.4-2006a NoV VLPs produced in Nicotiana benthamiana was investigated. BALB/c mice were immunized intradermally with suboptimal (0.3 µg) dose of each NoV VLP alone or combined with 10 µg of VP6, or equal doses of NoV VLPs and VP6 (1 µg/antigen). NoV-specific serum IgG antibodies and their blocking activity were analyzed using vaccine-homologous and heterologous NoV VLPs. Immunization with 0.3 µg NoV VLPs alone was insufficient to induce NoV-specific immune responses, but with co-administration of 10 µg of VP6, antibodies against vaccine-derived and heterologous NoV genotypes were generated. Furthermore, corresponding adjuvant effect of VP6 was observed with 1 µg dose. Efficient uptake and presentation of VP6 by dendritic cells was demonstrated in vitro. These results show that adjuvant effect of VP6 on bivalent NoV VLP vaccine is independent of the cell source used for vaccine production. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Figure 1

12 pages, 2024 KiB

Open AccessArticle

Mono- and Bi-Phasic Cellulose Acetate Micro-Vectors for Anti-Inflammatory Drug Delivery

by Vincenzo Guarino, Rosaria Altobelli, Tania Caputo, Luigi Ambrosio, Sergio Caserta, Paola Calcagnile and Christian Demitri

Pharmaceutics 2019, 11(2), 87; https://doi.org/10.3390/pharmaceutics11020087 - 18 Feb 2019

Cited by 11 | Viewed by 3213

Abstract

In recent years, different processing technologies have been engineered to fabricate capsules or particles with peculiar properties (e.g., swelling, pH-sensitive response) at the micro and sub-micrometric size scale, to be used as carriers for controlled drug and molecular release. Herein, the development of [...] Read more.

In recent years, different processing technologies have been engineered to fabricate capsules or particles with peculiar properties (e.g., swelling, pH-sensitive response) at the micro and sub-micrometric size scale, to be used as carriers for controlled drug and molecular release. Herein, the development of cellulose acetate (CA) micro-carriers with mono- (MC) or bi-phasic (BC) composition is proposed, fabricated via electrohydrodynamic atomization (EHDA)—an electro-dropping technology able to micro-size polymer solution by the application of high voltage electrostatic forces. Image analysis allows identification of the process parameters to optimize morphology, in terms of size distribution and shape. Meanwhile, an accurate rheological study has enabled investigating the interface between CA solutions with different viscosities to optimize BC systems. Release tests have confirmed that BC carriers can retain the drug more efficiently in acidic conditions, also providing a more gradual and sustained release until six days, with respect to MC carriers. Hence, all these results have proven that biphasic architecture significantly improves the capability of CA microcarriers to release ketoprofen lysinate, thus suggesting a new route to design core/shell systems for the retarded oral administration of anti-inflammatory drugs. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Graphical abstract

Review

Jump to: Research

38 pages, 1663 KiB

Open AccessReview

Breaking Barriers: Bioinspired Strategies for Targeted Neuronal Delivery to the Central Nervous System

by Ana P. Spencer, Marília Torrado, Beatriz Custódio, Sara C. Silva-Reis, Sofia D. Santos, Victoria Leiro and Ana P. Pêgo

Pharmaceutics 2020, 12(2), 192; https://doi.org/10.3390/pharmaceutics12020192 - 23 Feb 2020

Cited by 15 | Viewed by 4890

Abstract

Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective [...] Read more.

Central nervous system (CNS) disorders encompass a vast spectrum of pathological conditions and represent a growing concern worldwide. Despite the high social and clinical interest in trying to solve these pathologies, there are many challenges to bridge in order to achieve an effective therapy. One of the main obstacles to advancements in this field that has hampered many of the therapeutic strategies proposed to date is the presence of the CNS barriers that restrict the access to the brain. However, adequate brain biodistribution and neuronal cells specific accumulation in the targeted site also represent major hurdles to the attainment of a successful CNS treatment. Over the last few years, nanotechnology has taken a step forward towards the development of therapeutics in neurologic diseases and different approaches have been developed to surpass these obstacles. The versatility of the designed nanocarriers in terms of physical and chemical properties, and the possibility to functionalize them with specific moieties, have resulted in improved neurotargeted delivery profiles. With the concomitant progress in biology research, many of these strategies have been inspired by nature and have taken advantage of physiological processes to achieve brain delivery. Here, the different nanosystems and targeting moieties used to achieve a neuronal delivery reported in the open literature are comprehensively reviewed and critically discussed, with emphasis on the most recent bioinspired advances in the field. Finally, we express our view on the paramount challenges in targeted neuronal delivery that need to be overcome for these promising therapeutics to move from the bench to the bedside. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Graphical abstract

24 pages, 1340 KiB

Open AccessReview

Hydrogels Based Drug Delivery Synthesis, Characterization and Administration

by Anca Onaciu, Raluca Andrada Munteanu, Alin Iulian Moldovan, Cristian Silviu Moldovan and Ioana Berindan-Neagoe

Pharmaceutics 2019, 11(9), 432; https://doi.org/10.3390/pharmaceutics11090432 - 23 Aug 2019

Cited by 68 | Viewed by 9356

Abstract

Hydrogels represent 3D polymeric networks specially designed for various medical applications. Due to their porous structure, they are able to swollen and to entrap large amounts of therapeutic agents and other molecules. In addition, their biocompatibility and biodegradability properties, together with a controlled [...] Read more.

Hydrogels represent 3D polymeric networks specially designed for various medical applications. Due to their porous structure, they are able to swollen and to entrap large amounts of therapeutic agents and other molecules. In addition, their biocompatibility and biodegradability properties, together with a controlled release profile, make hydrogels a potential drug delivery system. In vivo studies have demonstrated their effectiveness as curing platforms for various diseases and affections. In addition, the results of the clinical trials are very encouraging and promising for the use of hydrogels as future target therapy strategies. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Figure 1

23 pages, 4449 KiB

Open AccessReview

Chemistry Routes for Copolymer Synthesis Containing PEG for Targeting, Imaging, and Drug Delivery Purposes

by Kamil Rahme and Nazih Dagher

Pharmaceutics 2019, 11(7), 327; https://doi.org/10.3390/pharmaceutics11070327 - 11 Jul 2019

Cited by 42 | Viewed by 9235

Abstract

Polyethylene glycol (PEG) is one of the most frequently used polymers for coating nanocarriers to enhance their biocompatibility, hydrophilicity, stability, and biodegradability. PEG is now considered to be among the best biocompatible polymers. It offers sterical hindrance against other nanoparticles and blood components [...] Read more.

Polyethylene glycol (PEG) is one of the most frequently used polymers for coating nanocarriers to enhance their biocompatibility, hydrophilicity, stability, and biodegradability. PEG is now considered to be among the best biocompatible polymers. It offers sterical hindrance against other nanoparticles and blood components such as opsonin, preventing their macrophage phagocytosis and resulting in a prolonged circulation time in blood stream, consequently a ‘stealth character’ in vivo. Therefore, PEG has a very promising future for the development of current therapeutics and biomedical applications. Moreover, the vast number of molecules that PEG can conjugate with might enhance its ability to have an optimistic perspective for the future. This review will present an update on the chemistry used in the modern conjugation methods for a variety of PEG conjugates, such methods include, but are not limited to, the synthesis of targeting PEG conjugates (i.e., Peptides, Folate, Biotin, Mannose etc.), imaging PEG conjugates (i.e., Coumarin, Near Infrared dyes etc.) and delivery PEG conjugates (i.e., doxorubicin, paclitaxel, and other hydrophobic low molecular weight drugs). Furthermore, the type of nanoparticles carrying those conjugates, along with their biomedical uses, will be briefly discussed. Full article

(This article belongs to the Special Issue Bioinspired Design in Drug Delivery)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Bioinspired Design in Drug Delivery

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI