Recent Advancements in Polymer/Liposome Assembly for Drug Delivery: From Surface Modifications to Hybrid Vesicles

Liposomes are consolidated and attractive biomimetic nanocarriers widely used in the field of drug delivery. The structural versatility of liposomes has been exploited for the development of various carriers for the topical or systemic delivery of drugs and bioactive molecules, with the possibility of increasing their bioavailability and stability, and modulating and directing their release, while limiting the side effects at the same time. Nevertheless, first-generation vesicles suffer from some limitations including physical instability, short in vivo circulation lifetime, reduced payload, uncontrolled release properties, and low targeting abilities. Therefore, liposome preparation technology soon took advantage of the possibility of improving vesicle performance using both natural and synthetic polymers. Polymers can easily be synthesized in a controlled manner over a wide range of molecular weights and in a low dispersity range. Their properties are widely tunable and therefore allow the low chemical versatility typical of lipids to be overcome. Moreover, depending on their structure, polymers can be used to create a simple covering on the liposome surface or to intercalate in the phospholipid bilayer to give rise to real hybrid structures. This review illustrates the main strategies implemented in the field of polymer/liposome assembly for drug delivery, with a look at the most recent publications without neglecting basic concepts for a simple and complete understanding by the reader.

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Chitosan Nanoparticles at the Biological Interface: Implications for Drug Delivery

Pharmaceutics ◽

10.3390/pharmaceutics13101686 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1686

Author(s):

Noorjahan Aibani ◽

Raj Rai ◽

Parth Patel ◽

Grace Cuddihy ◽

Ellen K. Wasan

Keyword(s):

Drug Delivery ◽

Cellular Uptake ◽

Chitosan Nanoparticles ◽

Chemical Properties ◽

Protein Corona ◽

Systemic Circulation ◽

Systemic Delivery ◽

Toxicological Evaluation ◽

Wide Range

The unique properties of chitosan make it a useful choice for various nanoparticulate drug delivery applications. Although chitosan is biocompatible and enables cellular uptake, its interactions at cellular and systemic levels need to be studied in more depth. This review focuses on the various physical and chemical properties of chitosan that affect its performance in biological systems. We aim to analyze recent research studying interactions of chitosan nanoparticles (NPs) upon their cellular uptake and their journey through the various compartments of the cell. The positive charge of chitosan enables it to efficiently attach to cells, increasing the probability of cellular uptake. Chitosan NPs are taken up by cells via different pathways and escape endosomal degradation due to the proton sponge effect. Furthermore, we have reviewed the interaction of chitosan NPs upon in vivo administration. Chitosan NPs are immediately surrounded by a serum protein corona in systemic circulation upon intravenous administration, and their biodistribution is mainly to the liver and spleen indicating RES uptake. However, the evasion of RES system as well as the targeting ability and bioavailability of chitosan NPs can be improved by utilizing specific routes of administration and covalent modifications of surface properties. Ongoing clinical trials of chitosan formulations for therapeutic applications are paving the way for the introduction of chitosan into the pharmaceutical market and for their toxicological evaluation. Chitosan provides specific biophysical properties for effective and tunable cellular uptake and systemic delivery for a wide range of applications.

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Degradation of Drug Delivery Nanocarriers and Payload Release: A Review of Physical Methods for Tracing Nanocarrier Biological Fate

Pharmaceutics ◽

10.3390/pharmaceutics13060770 ◽

2021 ◽

Vol 13 (6) ◽

pp. 770

Author(s):

Patrick M. Perrigue ◽

Richard A. Murray ◽

Angelika Mielcarek ◽

Agata Henschke ◽

Sergio E. Moya

Keyword(s):

Drug Delivery ◽

Laser Scanning ◽

Single Photon ◽

Photon Emission ◽

Correlation Spectroscopy ◽

Laser Scanning Microscopy ◽

Confocal Laser ◽

Emission Computed Tomography ◽

Systemic Delivery

Nanoformulations offer multiple advantages over conventional drug delivery, enhancing solubility, biocompatibility, and bioavailability of drugs. Nanocarriers can be engineered with targeting ligands for reaching specific tissue or cells, thus reducing the side effects of payloads. Following systemic delivery, nanocarriers must deliver encapsulated drugs, usually through nanocarrier degradation. A premature degradation, or the loss of the nanocarrier coating, may prevent the drug’s delivery to the targeted tissue. Despite their importance, stability and degradation of nanocarriers in biological environments are largely not studied in the literature. Here we review techniques for tracing the fate of nanocarriers, focusing on nanocarrier degradation and drug release both intracellularly and in vivo. Intracellularly, we will discuss different fluorescence techniques: confocal laser scanning microscopy, fluorescence correlation spectroscopy, lifetime imaging, flow cytometry, etc. We also consider confocal Raman microscopy as a label-free technique to trace colocalization of nanocarriers and drugs. In vivo we will consider fluorescence and nuclear imaging for tracing nanocarriers. Positron emission tomography and single-photon emission computed tomography are used for a quantitative assessment of nanocarrier and payload biodistribution. Strategies for dual radiolabelling of the nanocarriers and the payload for tracing carrier degradation, as well as the efficacy of the payload delivery in vivo, are also discussed.

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Mesoporous Silica Nanoparticles and Mesoporous Bioactive Glasses for Wound Management: From Skin Regeneration to Cancer Therapy

Materials ◽

10.3390/ma14123337 ◽

2021 ◽

Vol 14 (12) ◽

pp. 3337

Author(s):

Sara Hooshmand ◽

Sahar Mollazadeh ◽

Negar Akrami ◽

Mehrnoosh Ghanad ◽

Ahmed El-Fiqi ◽

...

Keyword(s):

Mesoporous Silica ◽

Silica Nanoparticles ◽

Mesoporous Silica Nanoparticles ◽

Skin Regeneration ◽

Bioactive Molecules ◽

Wound Management ◽

Bioactive Glasses ◽

Wide Range

Exploring new therapies for managing skin wounds is under progress and, in this regard, mesoporous silica nanoparticles (MSNs) and mesoporous bioactive glasses (MBGs) offer great opportunities in treating acute, chronic, and malignant wounds. In general, therapeutic effectiveness of both MSNs and MBGs in different formulations (fine powder, fibers, composites etc.) has been proved over all the four stages of normal wound healing including hemostasis, inflammation, proliferation, and remodeling. The main merits of these porous substances can be summarized as their excellent biocompatibility and the ability of loading and delivering a wide range of both hydrophobic and hydrophilic bioactive molecules and chemicals. In addition, doping with inorganic elements (e.g., Cu, Ga, and Ta) into MSNs and MBGs structure is a feasible and practical approach to prepare customized materials for improved skin regeneration. Nowadays, MSNs and MBGs could be utilized in the concept of targeted therapy of skin malignancies (e.g., melanoma) by grafting of specific ligands. Since potential effects of various parameters including the chemical composition, particle size/morphology, textural properties, and surface chemistry should be comprehensively determined via cellular in vitro and in vivo assays, it seems still too early to draw a conclusion on ultimate efficacy of MSNs and MBGs in skin regeneration. In this regard, there are some concerns over the final fate of MSNs and MBGs in the wound site plus optimal dosages for achieving the best outcomes that deserve careful investigation in the future.

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Exosomes containing miRNAs targeting HER2 synthesis and engineered to adhere to HER2 on tumor cells surface exhibit enhanced antitumor activity

10.21203/rs.3.rs-39552/v2 ◽

2020 ◽

Author(s):

Lei Wang ◽

Xusha Zhou ◽

Weixuan Zou ◽

Yinglin Wu ◽

Jing Zhao ◽

...

Keyword(s):

Drug Delivery ◽

Epidermal Growth Factor Receptor ◽

Growth Factor ◽

Epidermal Growth Factor ◽

Cancer Cells ◽

Tumor Cells ◽

Growth Factor Receptor ◽

Wide Range ◽

Epidermal Growth

Abstract Background: Exosomes are small, cellular membrane-derived vesicles with a diameter of 50-150 nm. Exosomes are considered ideal drug delivery systems with a wide range of applications in various diseases, including cancer. However, nonspecific delivery of therapeutic agents by exosomes in vivo remains challenging. H uman epidermal growth factor receptor 2 (HER2) is an epidermal growth factor receptor tyrosine kinase, and its overexpression is usually associated with cell survival and tumor progression in various cancers. In this study, we aim to develop novel exosomes with dual HER2-targeting ability as a nanoparticle delivery vehicle to enhance antitumor efficacy in vivo . Results: Here, we report the generation of two kinds of exosomes carrying miRNAs designed to block HER2 synthesis and consequently kill tumor cells. 293-miR-HER2 exosomes package and deliver designed miRNAs to cells to block HER2 synthesis. These exosomes kill cancer cells dependent on HER2 for survival but do not affect cells that lack HER2 or that are engineered to express HER2 but are not dependent on it for survival. In contrast, 293-miR-XS-HER2 exosomes carry an additional peptide, which enables them to adhere to HER2 on the surface of cancer cells. Consequently, these exosomes preferentially enter and kill cells with surface expression of HER2. 293-miR-XS-HER2 exosomes are significantly more effective than the 293-miR-HER2 exosomes in shrinking HER2-positive tumors implanted in mice. Conclusions: Collectively, as novel antitumor drug delivery vehicles, HER2 dual-targeting exosomes exhibit increased target-specific delivery efficiency and can be further utilized to develop new nanoparticle-based targeted therapies.

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A Review on Application of Novel Solid Nanostructures in Drug Delivery

Journal of Nano Research ◽

10.4028/www.scientific.net/jnanor.53.22 ◽

2018 ◽

Vol 53 ◽

pp. 22-36 ◽

Cited By ~ 4

Author(s):

Habibollah Faraji ◽

Reza Nedaeinia ◽

Esmaeil Nourmohammadi ◽

Bizan Malaekeh-Nikouei ◽

Hamid Reza Sadeghnia ◽

...

Keyword(s):

Drug Delivery ◽

Drug Therapy ◽

Biomedical Applications ◽

Imaging Biomarkers ◽

Cellular Functions ◽

Scientific Innovation ◽

Wide Range ◽

Targeted Drug

Nanotechnology as a multidisciplinary and scientific innovation plays an important role in numerous biomedical applications, such as molecular imaging, biomarkers and biosensors and also drug delivery. A wide range of studies have been conducted on using of nanoparticles for early diagnosis and targeted drug therapy of various diseases. In fact, the small size, customized surface, upgraded solubility, or multi-functionality of nanoparticles enabled them to interact with complex cellular functions in new ways which opened many doors and created new biomedical applications. These studies demonstrated that nanotechnology vehicles can formulate biological products effectively, and this nano-formulated products with a potent ability against different diseases, were represented to have better biocompatibility, bioaccessibility and efficacy, under in vitro and in vivo conditions.

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Erythrocytes as Carriers: From Drug Delivery to Biosensors

Pharmaceutics ◽

10.3390/pharmaceutics12030276 ◽

2020 ◽

Vol 12 (3) ◽

pp. 276 ◽

Cited By ~ 7

Author(s):

Larisa Koleva ◽

Elizaveta Bovt ◽

Fazoil Ataullakhanov ◽

Elena Sinauridze

Keyword(s):

Drug Delivery ◽

Targeted Drug Delivery ◽

Reticuloendothelial System ◽

In Vivo Studies ◽

Bioactive Substances ◽

Target Organs ◽

Wide Range ◽

Opening Up ◽

Gradual Release

Drug delivery using natural biological carriers, especially erythrocytes, is a rapidly developing field. Such erythrocytes can act as carriers that prolong the drug’s action due to its gradual release from the carrier; as bioreactors with encapsulated enzymes performing the necessary reactions, while remaining inaccessible to the immune system and plasma proteases; or as a tool for targeted drug delivery to target organs, primarily to cells of the reticuloendothelial system, liver and spleen. To date, erythrocytes have been studied as carriers for a wide range of drugs, such as enzymes, antibiotics, anti-inflammatory, antiviral drugs, etc., and for diagnostic purposes (e.g., magnetic resonance imaging). The review focuses only on drugs loaded inside erythrocytes, defines the main lines of research for erythrocytes with bioactive substances, as well as the advantages and limitations of their application. Particular attention is paid to in vivo studies, opening-up the potential for the clinical use of drugs encapsulated into erythrocytes.

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Albumin coated liposomes: a novel platform for macrophage specific drug delivery

Nanotechnology Development ◽

10.4081/nd.2011.e2 ◽

2011 ◽

Vol 1 (1) ◽

pp. 2 ◽

Cited By ~ 5

Author(s):

Clément Vuarchey ◽

Sushil Kumar ◽

Reto Schwendener

Keyword(s):

Drug Delivery ◽

Drug Carrier ◽

Cell Types ◽

Specific Drug ◽

Splenic Macrophages ◽

Peg Liposomes ◽

Short Time ◽

Liposome Surface

Here we report a new and efficient approach of macrophage specific drug delivery by coating liposomes with albumin. Activated albumin was reacted with liposomes containing polyethylene glycol (PEG) as hydrophilic spacers to create a flexible layer of covalently bound albumin molecules on the liposome surface. Albumin coated liposomes were taken up faster and more efficiently than uncoated liposomes by murine macrophages. Liposome uptake was significantly higher in macropha - ges as compared to other cell types tested (endothelial cells, fibroblasts, tumor cells), suggesting specificity for macrophages. In vivo, splenic macrophages phagocytosed BSA coated liposomes (BSA-L) at faster rates compared to conventional liposomes (L) and PEG liposomes (PEG-L). To prove the effectiveness of this new macrophage specific drug carrier, the bisphosphonates clodronate and zoledronate were encapsulated in BSA-L and compared with conventional liposomes. <em>In vitro</em>, treatment of macrophages with clodronate or zoledronate in BSA-L led to cytotoxic activity within a very short time and to up to 50-fold reduced IC50 concentrations. <em>In vivo</em>, clodronate encapsulated in BSA-L depleted splenic macrophages at a 5-fold lower concentration as conventional clodronate-liposomes. Our results highlight the pharmaceutical benefits of albumin-coated liposomes for macrophage specific drug delivery.

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Nutraceutical Activity in Osteoarthritis Biology: A Focus on the Nutrigenomic Role

Cells ◽

10.3390/cells9051232 ◽

2020 ◽

Vol 9 (5) ◽

pp. 1232

Author(s):

Stefania D’Adamo ◽

Silvia Cetrullo ◽

Veronica Panichi ◽

Erminia Mariani ◽

Flavio Flamigni ◽

...

Keyword(s):

Signaling Pathways ◽

Antioxidant Activities ◽

Synergistic Effects ◽

National Health System ◽

Bioactive Molecules ◽

Joint Disease ◽

In Vivo Studies ◽

Wide Range

Osteoarthritis (OA) is a disease associated to age or conditions that precipitate aging of articular cartilage, a post-mitotic tissue that remains functional until the failure of major homeostatic mechanisms. OA severely impacts the national health system costs and patients’ quality of life because of pain and disability. It is a whole-joint disease sustained by inflammatory and oxidative signaling pathways and marked epigenetic changes responsible for catabolism of the cartilage extracellular matrix. OA usually progresses until its severity requires joint arthroplasty. To delay this progression and to improve symptoms, a wide range of naturally derived compounds have been proposed and are summarized in this review. Preclinical in vitro and in vivo studies have provided proof of principle that many of these nutraceuticals are able to exert pleiotropic and synergistic effects and effectively counteract OA pathogenesis by exerting both anti-inflammatory and antioxidant activities and by tuning major OA-related signaling pathways. The latter are the basis for the nutrigenomic role played by some of these compounds, given the marked changes in the transcriptome, miRNome, and methylome. Ongoing and future clinical trials will hopefully confirm the disease-modifying ability of these bioactive molecules in OA patients.

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Elastic and Ultradeformable Liposomes for Transdermal Delivery of Active Pharmaceutical Ingredients (APIs)

International Journal of Molecular Sciences ◽

10.3390/ijms22189743 ◽

2021 ◽

Vol 22 (18) ◽

pp. 9743

Author(s):

Eliana B. Souto ◽

Ana S. Macedo ◽

João Dias-Ferreira ◽

Amanda Cano ◽

Aleksandra Zielińska ◽

...

Keyword(s):

Drug Delivery ◽

Transdermal Delivery ◽

Transdermal Drug Delivery ◽

Drug Delivery Systems ◽

First Generation ◽

Delivery Systems ◽

Topical Drug Delivery ◽

Active Pharmaceutical Ingredients ◽

Pharmaceutical Ingredients

Administration of active pharmaceutical ingredients (APIs) through the skin, by means of topical drug delivery systems, is an advanced therapeutic approach. As the skin is the largest organ of the human body, primarily acting as a natural protective barrier against permeation of xenobiotics, specific strategies to overcome this barrier are needed. Liposomes are nanometric-sized delivery systems composed of phospholipids, which are key components of cell membranes, making liposomes well tolerated and devoid of toxicity. As their lipid compositions are similar to those of the skin, liposomes are used as topical, dermal, and transdermal delivery systems. However, permeation of the first generation of liposomes through the skin posed some limitations; thus, a second generation of liposomes has emerged, overcoming permeability problems. Various mechanisms of permeation/penetration of elastic/ultra-deformable liposomes into the skin have been proposed; however, debate continues on their extent/mechanisms of permeation/penetration. In vivo bioavailability of an API administered in the form of ultra-deformable liposomes is similar to the bioavailability achieved when the same API is administered in the form of a solution by subcutaneous or epi-cutaneous injection, which demonstrates their applicability in transdermal drug delivery.

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Physicochemical characterization, toxicity and in vivo biodistribution studies of a discoidal, lipid-based drug delivery vehicle: Lipodisq nanoparticles containing doxorubicin

10.1101/2020.06.18.159087 ◽

2020 ◽

Author(s):

Maria Lyngaas Torgersen ◽

Peter J. Judge ◽

Juan F. Bada Juarez ◽

Abhilash D. Pandya ◽

Markus Fusser ◽

...

Keyword(s):

Drug Delivery ◽

Physicochemical Characterization ◽

Phospholipid Bilayer ◽

Drug Delivery Vehicles ◽

Carboxylate Groups ◽

Biodistribution Studies ◽

Aqueous Environments ◽

Delivery Vehicles ◽

Doxorubicin Release

AbstractMany promising pharmaceutically active compounds have low solubility in aqueous environments and their encapsulation into efficient drug delivery vehicles is crucial to increase their bioavailability. Lipodisq nanoparticles are approximately 10 nm in diameter and consist of a circular phospholipid bilayer, stabilized by an annulus of SMA (a hydrolysed copolymer of styrene and maleic anhydride). SMA is used extensively in structural biology to extract and stabilize integral membrane proteins for biophysical studies. Here, we assess the potential of these nanoparticles as drug delivery vehicles, determining their cytotoxicity and the in vivo excretion pathways of their polymer and lipid components. Doxorubicin-loaded Lipodisqs were cytotoxic across a panel of cancer cell lines, whereas nanoparticles without the drug had no effect on cell proliferation. Intracellular doxorubicin release from Lipodisqs in HeLa cells occurred in the low-pH environment of the endolysosomal system, consistent with the breakdown of the discoidal structure as the carboxylate groups of the SMA polymer become protonated. Biodistribution studies in mice showed that, unlike other nanoparticles injected intravenously, most of the Lipodisq components were recovered in the colon, consistent with rapid uptake by hepatocytes and excretion into bile. These data suggest that Lipodisqs have the potential to act as delivery vehicles for drugs and contrast agents.

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