| 1. |
- Cerrato, Carmine Pasquale, et al.
(författare)
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An update on cell-penetrating peptides with intracellular organelle targeting
- 2022
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Ingår i: Expert Opinion on Drug Delivery. - : Informa UK Limited. - 1742-5247 .- 1744-7593. ; 19:2, s. 133-146
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Forskningsöversikt (refereegranskat)abstract
- Introduction Cell-penetrating peptide (CPP) technologies represent an important strategy to address drug delivery to specific intracellular compartments by covalent conjugation to targeting sequences, potentially enabling strategies to combat most diseases.Areas covered This updated review article provides an overview of current intracellular organelle targeting by CPP. The targeting strategies of CPP and CPP/cargo complexes to specific cells or intracellular organelles are summarized, and the review provides an update on the current data for their pharmacological and therapeutical applications.Expert opinion Targeted drug delivery is moving from the level of tissue or specific pathogenic cell to the level of specific organelle that is the target of the drug, an important aspect in drug design and development. Organelle-targeted drug delivery results in improved efficacy, ability to control mode of action, reduction of undesired toxicities and side effects, and the possibility to overcome drug resistance mechanisms.
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| 2. |
- Cerrato, Carmine Pasquale, et al.
(författare)
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Cell-penetrating peptides with intracellular organelle targeting
- 2017
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Ingår i: Expert Opinion on Drug Delivery. - : Informa UK Limited. - 1742-5247 .- 1744-7593. ; 14:2, s. 245-255
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Forskningsöversikt (refereegranskat)abstract
- INTRODUCTION: One of the major limiting steps in order to have an effective drug is the passage through one or more cell membranes to reach its site of action. To reach the action-site, the specific macromolecules are required to be delivered specifically to the cell compartment/organelle in their (pre)active form.AREAS COVERED: In this review, we will discuss cell-penetrating peptides (CPPs) developed in the last decade to transport small RNA/DNA, plasmids, antibodies, and nanoparticles into specific sites of the cell. The article describes CPPs in complex with cargo molecules that target specific intracellular organelles and their potential for pharmacological or clinical use.EXPERT OPINION: Organelle targeting is the ultimate goal to ensure selective delivery to the site of action in the cells. CPP technologies represent an important strategy to address drug delivery to specific intracellular compartments by covalent conjugation to targeting sequences, potentially enabling strategies to combat genomic diseases as well as infections, cancer, neurodegenerative and hereditary diseases. They have proven to be successful in delivering various therapeutic agents into cells however, further in vivo experiments and clinical trials are required to demonstrate the efficacy of this technology.
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| 3. |
- Coelho, S. C., et al.
(författare)
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Gold nanoparticle delivery-enhanced proteasome inhibitor effect in adenocarcinoma cells
- 2013
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Ingår i: Expert Opinion on Drug Delivery. - : Informa Healthcare. - 1742-5247 .- 1744-7593. ; 10:10, s. 1345-1352
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Tidskriftsartikel (refereegranskat)abstract
- Background: Proteasome inhibition is a current therapeutic strategy used in the treatment of multiple myeloma. Drugs controlling proteasome activity are ideally suited for unidirectional manipulation of cellular pathways such as apoptosis. The first proteasome inhibitor approved in clinics was bortezomib. This drug is currently used in combination with other anticancer agents. Objectives: In this study, the enhancement of bortezomib activity was evaluated using gold nanoparticles coated with poly(ethylene glycol). The uptake mechanism of the gold nanoparticles in pancreatic cell lines, S2-013 and hTERT-HPNE, was assessed by laser scanning confocal microscopy (LSCM). Results: Pancreatic cancer cells internalized the nanoparticles together with the drug in few minutes through the formation of endocytic vesicles. This rapid uptake leads to an increase in the concentration and diffusion of bortezomib in the cytoplasm yielding an increased toxicity on the cells when compared to the drug alone. Conclusion: Gold nanoparticles can be used as effective delivery systems to increasing the permeation and retention of drugs in cancer cells.
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| 4. |
- Kandušer, Maša, et al.
(författare)
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Cell electrofusion: past and future perspectives for antibody production and cancer cell vaccines
- 2014
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Ingår i: Expert Opinion on Drug Delivery. - : Taylor & Francis. - 1742-5247 .- 1744-7593. ; 11:12, s. 1885-1898
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Tidskriftsartikel (refereegranskat)abstract
- Introduction: In the past few decades, new methods for drug and gene delivery have been developed, among which electroporation and electrofusion have gained noticeable attention. Lately, advances in the field of immunotherapy have enabled new cancer therapies based on immune response, including monoclonal antibodies and cell vaccines. Efficient cell fusion is needed for both hybridoma production and cell vaccine preparation, and electrofusion is a promising method to achieve this goal.Areas covered: In the present review, we cover new strategies of cancer treatment related to antibody production and cell vaccines. In more detail, cell electroporation and electrofusion are addressed. We briefly describe principles of cell electroporation and focus on electrofusion and its influential factors, with special attention on the fusogenic state of the cell membrane, contact formation, the effect of electrofusion media and cell viability. We end the review with an overview of the very promising field of microfluidic devices for electrofusion.Expert opinion: In our opinion, electrofusion can be a very efficient method for hybridoma and cell vaccine production. Advances in the development of microfluidic devices and a better understanding of the underlying (biological) mechanisms will overcome the current limitations.
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| 5. |
- Kurrikoff, Kaido, et al.
(författare)
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Recent CPP-based applications in medicine
- 2019
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Ingår i: Expert Opinion on Drug Delivery. - : Informa UK Limited. - 1742-5247 .- 1744-7593. ; 16:11, s. 1183-1191
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Cell-penetrating peptides (CPP) offer versatile tools for the field of drug delivery and development of macromolecular therapeutics. These tools have matured into applications that allow the use of proteins, nucleic acid, peptides, imaging agents, and low molecular weight drugs as therapeutic entities.Areas covered: The progress of the field is discussed in the current review, with the examples from a recent couple of years, in the utilization of CPPs in medicine. Specific focus is on the research articles that include applications that have direct translational value. Progress with protein mimicry and its recent leap in medicine is discussed with special attention, but also achievements with nanoformulation and drug targeting is presented.Expert opinion: The opinion section discusses some of the limitations and shortcomings, proposing the areas where more effort should be invested in order to increase the translational value of the current preclinical research.
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| 6. |
- Kurrikoff, Kaido, et al.
(författare)
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Recent in vivo advances in cell-penetrating peptide-assisted drug delivery
- 2016
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Ingår i: Expert Opinion on Drug Delivery. - : Informa Healthcare. - 1742-5247 .- 1744-7593. ; 13:3, s. 373-387
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Delivery of macromolecular drugs is an important field in medical research. However, macromolecules are usually unable to cross the cell membrane without the assistance of a delivery system. Cell penetrating peptides (CPPs) are unique tools to gain access to the cell interior and deliver a bioactive cargo into the cytosol or nucleus. In addition to macromolecular delivery, CPPs have been used to deliver smaller bioactive molecules. Therefore CPPs have become an intensive field of research for medical treatment.Areas covered: In this review, we highlight studies that include CPP in vivo disease models. We review different strategies and approaches that have been used, with specific attention on recent publications. The approaches that have been used include CPP–cargo covalent conjugation strategies and nanoparticle strategies. Various additional strategies have been used to achieve disease targeting, including active targeting, passive targeting, and combined active/passive strategies. As a result, delivery of various types of molecule has been achieved, including small drug molecules, proteins and nucleic acid-based macromolecules (e.g. siRNA, antisense nucleotides and plasmid DNA).Expert Opinion: Despite recent advances in the field, confusions surrounding CPP internalization mechanisms and intracellular trafficking are hindering the development of new and more efficient vectors. Nevertheless, the recent increase in the number of publications containing in vivo CPP utilization looks promising that the number of clinical trials would also increase in the near future.
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| 7. |
- Lavorini, Federico, et al.
(författare)
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Switching from branded to generic inhaled medications: potential impact on asthma and COPD
- 2013
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Ingår i: Expert Opinion on Drug Delivery. - : Informa Healthcare. - 1742-5247 .- 1744-7593. ; 10:12, s. 1597-1602
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Pressure on healthcare budgets is increasing, while at the same time patent protection for many branded inhaled medications has expired, leading to the development and growing availability of generic inhaled medicines. Generic inhaled drugs are therapeutically equivalent to original branded options but may differ in their formulation and inhalation device. This new situation raises questions about the potential impact of switching from branded to generic drug/inhaler combination products in patients with asthma or COPD, with or without their consent, in countries where this is permitted. Inhalation devices, particularly dry powder inhalers, vary markedly in their design, method of operation and drug delivery to the lungs. Current guidelines stress the importance of training patients how to use their inhalers but offer little or no guidance on how this should be achieved. Non-adherence to therapy and incorrect inhaler usage are recognised as major factors in poorly or uncontrolled asthma and COPD and switching patients to a different inhaler device may exacerbate these problems, particularly in patients who disagree to switch. Where switching is permitted or mandatory, adequate patient instruction and follow-up monitoring should be provided routinely.
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| 8. |
- Lehto, Taavi, et al.
(författare)
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Cell-penetrating peptides for the delivery of nucleic acids
- 2012
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Ingår i: Expert Opinion on Drug Delivery. - : Informa UK Limited. - 1742-5247 .- 1744-7593. ; 9:7, s. 823-836
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Different gene therapy approaches have gained extensive interest lately and, after many initial hurdles, several promising approaches have reached to the clinics. Successful implementation of gene therapy is heavily relying on finding efficient measures to deliver genetic material to cells. Recently, non-viral delivery of nucleic acids and their analogs has gained significant interest. Among non-viral vectors, cell-penetrating peptides (CPPs) have been extensively used for the delivery of nucleic acids both in vitro and in vivo. Areas covered: In this review we will discuss recent advances of CPP-mediated delivery of nucleic acid-based cargo, concentrating on the delivery of plasmid DNA, splice-correcting ONs, and small-interfering RNAs. Expert opinion: CPPs have proved their potential as carriers for nucleic acids. However, similarly to other non-viral vectors, CPPs require further development, as efficient systemic delivery is still seldom achieved. To achieve this, CPPs should be modified with entities that would allow better endosomal escape, targeting of specific tissues and cells, and shielding agents that increase the half-life of the vehicles. Finally, to understand the clinical potential of CPPs, they require more thorough investigations in clinically relevant disease models and in pre-clinical and clinical studies.
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| 9. |
- Lönn, Peter, et al.
(författare)
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Cationic PTD/CPP-mediated macromolecular delivery : charging into the cell
- 2015
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Ingår i: Expert Opinion on Drug Delivery. - : Informa Healthcare. - 1742-5247 .- 1744-7593. ; 12:10, s. 1627-1636
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Macromolecular therapeutics, including enzymes, transcription factors, siRNAs, peptides and large synthetic molecules, can potentially be used to treat human diseases by targeting intracellular molecular pathways and modulating biological responses. However, large macromolecules have no ability to enter cells and require delivery vehicles. Protein transduction domains (PTDs), also known as cell-penetrating peptides (CPPs), are a diverse class of peptides that can deliver macromolecules into cells.Areas covered: In this review, we cover the uptake and usage of arginine-rich PTDs/CPPs (TAT-PTD, Penetratin/Antp and 8R). We review the endocytosis-mediated uptake of these peptides and highlight three important steps: i) cell association; ii) internalization and iii) endosomal escape. We also discuss the array of different cargos that have been delivered by cationic PTDs/CPPs as well as cellular processes and biological responses that have been modulated.Expert opinion: PTDs/CPPs have shown great potential to deliver otherwise undeliverable macromolecular therapeutics into cells for experimentation in cell culture and in animal disease models in vivo. Moreover, over 25 clinical trials have been performed predominantly using the TAT-PTD. However, more work is still needed. Endosomal escape and target-cell specificity remain two of the major future challenges.
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| 10. |
- Maghrebi, Sajedehsadat, et al.
(författare)
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An update on polymer-lipid hybrid systems for improving oral drug delivery
- 2019
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Ingår i: Expert Opinion on Drug Delivery. - : Informa UK Limited. - 1742-5247 .- 1744-7593. ; 16:5, s. 507-524
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Forskningsöversikt (refereegranskat)abstract
- Introduction: A promising approach that has recently emerged to overcome the complex biobarriers and interrelated challenges associated with oral drug absorption is to combine the benefits of polymeric and lipid-based nanocarriers within one hybrid system. This multifaceted formulation strategy has given rise to a plethora of polymer-lipid hybrid (PLH) systems with varying nanostructures and biological activities, all of which have demonstrated the ability to improve the biopharmaceutical performance of a wide range of challenging therapeutics. Areas covered: The multitude of polymers that can be combined with lipids to exert a synergistic effect for oral drug delivery have been identified, reviewed and critically evaluated. Specific focus is attributed to preclinical studies performed within the past 5 years that have elucidated the role and mechanism of the polymer phase in altering the oral absorption of encapsulated therapeutics. Expert opinion: The potential of PLH systems has been clearly identified; however, improved understanding of the structure-activity relationship between PLH systems and oral absorption is fundamental for translating this promising delivery approach into a clinically relevant formulation. Advancing research within this field to identify optimal polymer, lipid combinations and engineering conditions for specific therapeutics are therefore encouraged.
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