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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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Polysaccharide/mesoporous silica nanoparticle-based drug delivery systems: A review.
Kuang, Y, Zhai, J, Xiao, Q, Zhao, S, Li, C
International journal of biological macromolecules. 2021;(Pt A):457-473
Abstract
Mesoporous silica nanoparticles (MSNs) have been well-researched in the design and fabrication of advanced drug delivery systems (DDSs) due to their advantages such as good biocompatibility, large specific surface area and pore volume for drug loading, easily surface modification, adjusted size and good thermal/chemical stability. For MSN-based DDSs, gate materials are also necessary. And natural polysaccharides, one kind of the most abundant natural resource, have been widely applied as the "gatekeepers" in MSN-based DDSs. Polysaccharides are cheap and rich in sources with good biocompatibility, and some of them have important biological functions. In this review article, polysaccharides including chitosan, hyaluronic acid, sodium alginate and dextran, et al. are briefly introduced. And the preparation processes and properties such as controlled drug release, cancer targeting and disease diagnosis of functional polysaccharide/MSN-based DDSs are discussed.
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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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Lactoferrin coated or conjugated nanomaterials as an active targeting approach in nanomedicine.
Agwa, MM, Sabra, S
International journal of biological macromolecules. 2021;:1527-1543
Abstract
A successful drug delivery to a specific site relies on two essential factors including; efficient entrapment of the drug within the carrier and successful delivery of drug- loaded nanocarrier to the target site without opsonisation or drug release in the circulation before reaching the organ of interest. Lactoferrin (LF) is a glycoprotein belonging to the transferrin (TF) family which can bind to TF receptors (TFRs) and LF membrane internalization receptors (LFRs) highly expressed on the cell surface of both highly proliferating cancer cells and blood brain barrier (BBB), which in turn can facilitate its accessibility to the cell nucleus. This merit could be exploited to develop actively targeted drug delivery systems that can easily cross the BBB or internalize into tumor cells. In this review, the most recent advances of utilizing LF as an active targeting ligand for different types of nanocarriers including: inorganic nanoparticles, dendrimers, synthetic biodegradable polymers, lipid nanocarriers, natural polymers, and nanoemulstions will be highlighted. Collectively, LF seems to be a promising targeting ligand in the field of nanomedicine.
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Oral Drug Delivery: Conventional to Long Acting New-Age Designs.
Bhutani, U, Basu, T, Majumdar, S
European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V. 2021;:23-42
Abstract
The Oral route of administration forms the heartwood of the ever-growing tree of drug delivery technology. It is one of the most preferred dosage forms among patients and controlled release community. Despite the high patient compliance, the deliveries of anti-cancerous drugs, vaccines, proteins, etc. via the oral route are limited and have recorded a very low bioavailability. The oral administration must overcome the physiological barriers (low solubility, permeation and early degradation) to achieve efficient and sustained delivery. This review aims at highlighting the conventional and modern-age strategies that address some of these physiological barriers. The modern age designs include the 3D printed devices and formulations. The superiority of 3D dosage forms over conventional cargos is summarized with a focus on long-acting designs. The innovations in Pharmaceutical organizations (Lyndra, Assertio and Intec) that have taken giant steps towards commercialization of long-acting vehicles are discussed. The recent advancements made in the arena of oral peptide delivery are also highlighted. The review represents a comprehensive journey from Nano-formulations to micro-fabricated oral implants aiming at specific patient-centric designs.
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The importance of co-delivery of nanoparticle-siRNA and anticancer agents in cancer therapy.
Khelghati, N, Soleimanpour Mokhtarvand, J, Mir, M, Alemi, F, Asemi, Z, Sadeghpour, A, Maleki, M, Samadi Kafil, H, Jadidi-Niaragh, F, Majidinia, M, et al
Chemical biology & drug design. 2021;(4):997-1015
Abstract
According to global statistics, cancer is the second leading cause of death worldwide. Because of the heterogeneity of cancer, single-drug therapy has many limitations due to low efficacy. Therefore, combination therapy with two or more therapeutic agents is being arisen. One of the most important approaches in cancer therapy is the shot down of key genes involved in apoptotic processes and cell cycle. In this regard, siRNA is a good candidate, a highly attractive method to suppressing tumor growth and invasion. Combination therapy with siRNAs and chemotherapeutic agents can overcome the multidrug resistance and increase apoptosis. The efficient delivery of siRNA to the target cell/tissue/organ has been a challenge. To overcome these challenges, the presence of suitable delivery systems by using nanoparticles is interesting. In this review, we discuss the current challenges for successful RNA interference. Also, we suggested proper a strategy for delivering siRNA that can be useful in targeting therapy. Finally, the combination of a variety of anticancer drugs and siRNA through acceptable delivery systems and their effects on cell cycle and apoptosis will be evaluated.
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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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Polymer - Metal Nanocomplexes Based Delivery System: A Boon for Agriculture Revolution.
Kaur, P, Choudhary, R, Pal, A, Mony, C, Adholeya, A
Current topics in medicinal chemistry. 2020;(11):1009-1028
Abstract
Metal nanoparticles are well known for their antimicrobial properties. The use of metalbased nanoparticles in the agricultural field has considerably increased globally by both direct and indirect means for the management of plant diseases. In this context, the development of controlled delivery systems for slow and sustained release of metal nanoparticles is crucial for prolonged antimicrobial activity. Polymers have emerged as a valuable carrier for controlled delivery of metal nanoparticles as agrochemicals because of their distinctive properties. The most significant benefits of encapsulating metal nanoparticles in a polymer matrix include the ability to function as a protector of metal nanoparticles and their controlled release with prolonged efficacy. This review focuses on loading strategies and releasing behavior of metal nanoparticles in the polymer matrix as antimicrobial agents for plant diseases. The Polymer-metal nanocomplexes (PMNs) comprise a biocompatible polymeric matrix and metal nanoparticles as active components of an antimicrobial agent, pesticides and plant growth regulators used to enhance the crop productivity.