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1.
Oral delivery of therapeutic peptides and proteins: Technology landscape of lipid-based nanocarriers.
Haddadzadegan, S, Dorkoosh, F, Bernkop-Schnürch, A
Advanced drug delivery reviews. 2022;:114097
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Abstract
The oral administration of therapeutic peptides and proteins is favoured from a patient and commercial point of view. In order to reach the systemic circulation after oral administration, these drugs have to overcome numerous barriers including the enzymatic, sulfhydryl, mucus and epithelial barrier. The development of oral formulations for therapeutic peptides and proteins is therefore necessary. Among the most promising formulation approaches are lipid-based nanocarriers such as oil-in-water nanoemulsions, self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC), liposomes and micelles. As the lipophilic character of therapeutic peptides and proteins can be tremendously increased such as by the formation of hydrophobic ion pairs (HIP) with hydrophobic counter ions, they can be incorporated in the lipophilic phase of these carriers. Since gastrointestinal (GI) peptidases as well as sulfhydryl compounds such as glutathione and dietary proteins are too hydrophilic to enter the lipophilic phase of these carriers, the incorporated therapeutic peptide or protein is protected towards enzymatic degradation as well as unintended thiol/disulfide exchange reactions. Stability of lipid-based nanocarriers towards lipases can be provided by the use to excipients that are not or just poorly degraded by these enzymes. Nanocarriers with a size <200 nm and a mucoinert surface such as PEG or zwitterionic surfaces exhibit high mucus permeating properties. Having reached the underlying absorption membrane, lipid-based nanocarriers enable paracellular and lymphatic drug uptake, induce endocytosis and transcytosis or simply fuse with the cell membrane releasing their payload into the systemic circulation. Numerous in vivo studies provide evidence for the potential of these delivery systems. Within this review we provide an overview about the different barriers for oral peptide and protein delivery, highlight the progress made on lipid-based nanocarriers in order to overcome them and discuss strengths and weaknesses of these delivery systems in comparison to other technologies.
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Solid-in-Oil-in-Water Emulsion: An Innovative Paradigm to Improve Drug Stability and Biological Activity.
Sawant, A, Kamath, S, Kg, H, Kulyadi, GP
AAPS PharmSciTech. 2021;(5):199
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Abstract
An emulsion is a biphasic dosage form comprising of dispersed phase containing droplets that are uniformly distributed into a surrounding liquid which forms the continuous phase. An emulsifier is added at the interface of two immiscible liquids to stabilize the thermodynamically unstable emulsion. Various types of emulsions such as water-in-oil (w-o), oil-in-water (o-w), microemulsions, and multiple emulsions are used for delivering certain drugs in the body. Water (aqueous) phase is commonly used for encapsulating proteins and several other drugs in water-in-oil-in-water (w-o-w) emulsion technique. But this method has posed certain problems such as decreased stability, burst release, and low entrapment efficiency. Thus, a novel "solid-in-oil-in-water" (s-o-w) emulsion system was developed for formulating certain drugs, probiotics, proteins, antibodies, and tannins to overcome these issues. In this method, the active ingredient is encapsulated as a solid and added to an oil phase, which formed a solid-oil dispersion. This dispersion was then mixed with water to form a continuous phase for enhancing the drug absorption. This article focuses on the various studies done to investigate the effectiveness of formulations prepared as solid-oil-water emulsions in comparison to conventional water-oil-water emulsions. A summary of the results obtained in each study is presented in this article. The s-o-w emulsion technique may become beneficial in near future as it has shown to improve the stability and efficacy of the entrapped active ingredient.
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Nano-Derived Therapeutic Formulations with Curcumin in Inflammation-Related Diseases.
Quispe, C, Cruz-Martins, N, Manca, ML, Manconi, M, Sytar, O, Hudz, N, Shanaida, M, Kumar, M, Taheri, Y, Martorell, M, et al
Oxidative medicine and cellular longevity. 2021;:3149223
Abstract
Due to its vast therapeutic potential, the plant-derived polyphenol curcumin is utilized in an ever-growing number of health-related applications. Here, we report the extraction methodologies, therapeutic properties, advantages and disadvantages linked to curcumin employment, and the new strategies addressed to improve its effectiveness by employing advanced nanocarriers. The emerging nanotechnology applications used to enhance CUR bioavailability and its targeted delivery in specific pathological conditions are collected and discussed. In particular, new aspects concerning the main strategic nanocarriers employed for treating inflammation and oxidative stress-related diseases are reported and discussed, with specific emphasis on those topically employed in conditions such as wounds, arthritis, or psoriasis and others used in pathologies such as bowel (colitis), neurodegenerative (Alzheimer's or dementia), cardiovascular (atherosclerosis), and lung (asthma and chronic obstructive pulmonary disease) diseases. A brief overview of the relevant clinical trials is also included. We believe the review can provide the readers with an overview of the nanostrategies currently employed to improve CUR therapeutic applications in the highlighted pathological conditions.
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Development of Lipid Nanoparticles for the Delivery of Macromolecules Based on the Molecular Design of pH-Sensitive Cationic Lipids.
Sato, Y
Chemical & pharmaceutical bulletin. 2021;(12):1141-1159
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Abstract
Considerable efforts have been made on the development of lipid nanoparticles (LNPs) for delivering of nucleic acids in LNP-based medicines, including a first-ever short interfering RNA (siRNA) medicine, Onpattro, and the mRNA vaccines against the coronavirus disease 2019 (COVID-19), which have been approved and are currently in use worldwide. The successful rational design of ionizable cationic lipids was a major breakthrough that dramatically increased delivery efficiency in this field. The LNPs would be expected to be useful as a platform technology for the delivery of various therapeutic modalities for genome editing and even for undiscovered therapeutic mechanisms. In this review, the current progress of my research, including the molecular design of pH-sensitive cationic lipids, their applications for various tissues and cell types, and for delivering various macromolecules, including siRNA, antisense oligonucleotide, mRNA, and the clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system will be described. Mechanistic studies regarding relationships between the physicochemical properties of LNPs, drug delivery, and biosafety are also summarized. Furthermore, current issues that need to be addressed for next generation drug delivery systems are discussed.
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Recent Advances in Nanotechnology for the Treatment of Melanoma.
Cassano, R, Cuconato, M, Calviello, G, Serini, S, Trombino, S
Molecules (Basel, Switzerland). 2021;(4)
Abstract
Melanoma is one of the most aggressive forms of skin cancer, with few possibilities for therapeutic approaches, due to its multi-drug resistance and, consequently, low survival rate for patients. Conventional therapies for treatment melanoma include radiotherapy, chemotherapy, targeted therapy, and immunotherapy, which have various side effects. For this reason, in recent years, pharmaceutical and biomedical research has focused on new sito-specific alternative therapeutic strategies. In this regard, nanotechnology offers numerous benefits which could improve the life expectancy of melanoma patients with very low adverse effects. This review aims to examine the latest advances in nanotechnology as an innovative strategy for treating melanoma. In particular, the use of different types of nanoparticles, such as vesicles, polymers, metal-based, carbon nanotubes, dendrimers, solid lipid, microneedles, and their combination with immunotherapies and vaccines will be discussed.
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Natural products and phytochemical nanoformulations targeting mitochondria in oncotherapy: an updated review on resveratrol.
Ashrafizadeh, M, Javanmardi, S, Moradi-Ozarlou, M, Mohammadinejad, R, Farkhondeh, T, Samarghandian, S, Garg, M
Bioscience reports. 2020;(4)
Abstract
Mitochondria are intracellular organelles with two distinct membranes, known as an outer mitochondrial membrane and inner cell membrane. Originally, mitochondria have been derived from bacteria. The main function of mitochondria is the production of ATP. However, this important organelle indirectly protects cells by consuming oxygen in the route of energy generation. It has been found that mitochondria are actively involved in the induction of the intrinsic pathways of apoptosis. So, there have been efforts to sustain mitochondrial homeostasis and inhibit its dysfunction. Notably, due to the potential role of mitochondria in the stimulation of apoptosis, this organelle is a promising target in cancer therapy. Resveratrol is a non-flavonoid polyphenol that exhibits significant pharmacological effects such as antioxidant, anti-diabetic, anti-inflammatory and anti-tumor. The anti-tumor activity of resveratrol may be a consequence of its effect on mitochondria. Multiple studies have investigated the relationship between resveratrol and mitochondria, and it has been demonstrated that resveratrol is able to significantly enhance the concentration of reactive oxygen species, leading to the mitochondrial dysfunction and consequently, apoptosis induction. A number of signaling pathways such as sirtuin and NF-κB may contribute to the mitochondrial-mediated apoptosis by resveratrol. Besides, resveratrol shifts cellular metabolism from glycolysis into mitochondrial respiration to induce cellular death in cancer cells. In the present review, we discuss the possible interactions between resveratrol and mitochondria, and its potential application in cancer therapy.
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Food-Derived Nanoscopic Drug Delivery Systems for Treatment of Rheumatoid Arthritis.
Han, D, Chen, Q, Chen, H
Molecules (Basel, Switzerland). 2020;(15)
Abstract
Rheumatoid arthritis (RA) is a severe systemic inflammatory disease with no cure at present. Recent developments in the understanding of inflammation and nanomaterial science have led to increased applications of nanostructured drug delivery systems in the treatment of RA. The present review summarizes novel fabrications of nanoscale drug carriers using food components as either the delivered drugs or carrier structures, in order to achieve safe, effective and convenient drug administration. Polyphenols and flavonoids are among the most frequently carried anti-RA therapeutics in the nanosystems. Fatty substances, polysaccharides, and peptides/proteins can function as structuring agents of the nanocarriers. Frequently used nanostructures include nanoemulsions, nanocapsules, liposomes, and various nanoparticles. Using these nanostructures has improved drug solubility, absorption, biodistribution, stability, targeted accumulation, and release. Joint vectorization, i.e., using a combination of bioactive molecules, can bring elevated therapeutic outcomes. Utilization of anti-arthritic chemicals that can self-assemble into nanostructures is a promising research orientation in this field.
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Review of Curcumin Physicochemical Targeting Delivery System.
Li, L, Zhang, X, Pi, C, Yang, H, Zheng, X, Zhao, L, Wei, Y
International journal of nanomedicine. 2020;:9799-9821
Abstract
Curcumin (CUR), as a traditional Chinese medicine monomer extracted from the rhizomes of some plants in Ginkgo and Araceae, has shown a wide range of therapeutic and pharmacological activities such as anti-tumor, anti-inflammatory, anti-oxidation, anti-virus, anti-liver fibrosis, anti-atherosclerosis, and anti-Alzheimer's disease. However, some issues significantly affect its biological activity, such as low aqueous solubility, physico-chemical instability, poor bioavailability, and low targeting efficacy. In order to further improve its curative effect, numerous efficient drug delivery systems have been carried out. Among them, physicochemical targeting preparations could improve the properties, targeting ability, and biological activity of CUR. Therefore, in this review, CUR carrier systems are discussed that are driven by physicochemical characteristics of the microenvironment (eg, pH variation of tumorous tissues), affected by external influences like magnetic fields and vehicles formulated with thermo-sensitive materials.
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Oral Nano Drug Delivery Systems for the Treatment of Type 2 Diabetes Mellitus: An Available Administration Strategy for Antidiabetic Phytocompounds.
Nie, X, Chen, Z, Pang, L, Wang, L, Jiang, H, Chen, Y, Zhang, Z, Fu, C, Ren, B, Zhang, J
International journal of nanomedicine. 2020;:10215-10240
Abstract
In view of the worldwide serious health threat of type 2 diabetes mellitus (T2DM), natural sources of chemotherapies have been corroborated as the promising alternatives, with the excellent antidiabetic activities, bio-safety, and more cost-effective properties. However, their clinical application is somewhat limited, because of the poor solubility, instability in the gastrointestinal tract (GIT), low bioavailability, and so on. Nowadays, to develop nanoscaled systems has become a prominent strategy to improve the drug delivery of phytochemicals. In this review, we primarily summarized the intervention mechanisms of phytocompounds against T2DM and presented the recent advances in various nanosystems of antidiabetic phytocompounds. Selected nanosystems were grouped depending on their classification and structures, including polymeric NPs, lipid-based nanosystems, vesicular systems, inorganic nanocarriers, and so on. Based on this review, the state-of-the-art nanosystems for phytocompounds in T2DM treatment have been presented, suggesting the preponderance and potential of nanotechnologies.
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Topical Administration of Terpenes Encapsulated in Nanostructured Lipid-Based Systems.
Lasoń, E
Molecules (Basel, Switzerland). 2020;(23)
Abstract
Terpenes are a group of phytocompounds that have been used in medicine for decades owing to their significant role in human health. So far, they have been examined for therapeutic purposes as antibacterial, anti-inflammatory, antitumoral agents, and the clinical potential of this class of compounds has been increasing continuously as a source of pharmacologically interesting agents also in relation to topical administration. Major difficulties in achieving sustained delivery of terpenes to the skin are connected with their low solubility and stability, as well as poor cell penetration. In order to overcome these disadvantages, new delivery technologies based on nanostructures are proposed to improve bioavailability and allow controlled release. This review highlights the potential properties of terpenes loaded in several types of lipid-based nanocarriers (liposomes, solid lipid nanoparticles, and nanostructured lipid carriers) used to overcome free terpenes' form limitations and potentiate their therapeutic properties for topical administration.