Article
Multidisciplinary Sciences
Andrea Barba-Bon, Giulia Salluce, Irene Lostale-Seijo, Khaleel Assaf, Andreas Hennig, Javier Montenegro, Werner M. Nau
Summary: This study demonstrates that globular dodecaborate clusters can function as anionic inorganic membrane carriers for a wide range of hydrophilic cargo molecules. These carriers have the potential to transport peptides, amino acids, neurotransmitters, vitamins, antibiotics, and drugs across liposomal membranes, and affect the cytosolic uptake of various small bioactive molecules.
Review
Medicine, Research & Experimental
Sofia Parrasia, Ildiko Szabo, Mario Zoratti, Lucia Biasutto
Summary: Central nervous system diseases are difficult to treat due to the blood-brain barrier (BBB), which prevents most drugs from reaching the brain. Peptides show promise in helping drugs cross the BBB and target the brain. However, there are challenges such as potential toxic effects, short in vivo lifespan, and inadequate drug levels in the brain.
MOLECULAR PHARMACEUTICS
(2022)
Review
Pharmacology & Pharmacy
Soma Mondal Ghorai, Auroni Deep, Devanshi Magoo, Chetna Gupta, Nikesh Gupta
Summary: Among the challenges in the 21st-century health care industry, the transport of drugs across the blood-brain barrier (BBB) is particularly difficult. The tight junctions within the brain capillary endothelium hinder the uptake of most pharmaceutical agents. This review focuses on the use of cell-penetrating peptides (CPPs) and homing/targeted peptides as intracellular drug delivery agents, especially for crossing the BBB.
Article
Biochemistry & Molecular Biology
Keisuke Tsuchiya, Kanako Horikoshi, Minami Fujita, Motoharu Hirano, Maho Miyamoto, Hidetomo Yokoo, Yosuke Demizu
Summary: Researchers have developed hydrophobic CPPs based on the hydrophobic CPP TP10 by introducing an aliphatic carbon side chain. These stapled peptides maintained the hydrophobicity of TP10, enhanced helicity, and improved cell-penetrating efficiency. The stapled peptide F-3 with CF showed stable α-helical structure and highest cell-membrane permeability, while peptide F-4 exhibited remarkable stability in complex formation with pDNA for efficient intracellular delivery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Hidetomo Yokoo, Makoto Oba, Satoshi Uchida
Summary: This article highlights the distinctive features of CPP-based mRNA delivery systems, including improved mRNA bioavailability, selective targeting of dendritic cells, efficient antigen presentation, and effective mRNA delivery to the lungs by dry powder inhalation.
Article
Chemistry, Multidisciplinary
Wufa Fan, Qiuyu Wei, Jiajia Xiang, Yisi Tang, Quan Zhou, Yu Geng, Yanpeng Liu, Rui Sun, Lei Xu, Guowei Wang, Ying Piao, Shiqun Shao, Zhuxian Zhou, Jianbin Tang, Tao Xie, Zichen Li, Youqing Shen
Summary: The study introduces a novel polymeric micelle that can penetrate mucus layer and be absorbed by villi, efficiently delivering anticancer drugs to tumors with improved therapeutic efficacy.
ADVANCED MATERIALS
(2022)
Review
Chemistry, Multidisciplinary
Yue-Xuan Li, Hong-Bo Pang
Summary: The endocytic pathways are crucial for the uptake of nanoparticles into cells and subcellular compartments. Macropinocytosis stands out for its unique ability to engulf large cargo, though its molecular mechanisms and role in nanoparticle uptake are not well understood. This review focuses on the macropinocytic machinery and its involvement in nanoparticle internalization, highlighting the synergistic effect between ligand-functionalized and unfunctionalized nanoparticles. The regulation of nanoparticle uptake efficiency by extracellular amino acids and the interconnectedness of macropinocytosis, metabolism, and nanomedicine are also discussed to inspire future research.
JOURNAL OF CONTROLLED RELEASE
(2021)
Article
Chemistry, Multidisciplinary
Takaaki Miyamoto, Kousuke Tsuchiya, Keiji Numata
Summary: A strategy utilizing endosome-escaping micelles with dual peptide modification has been developed for efficient intracellular DNA delivery to plants, overcoming vacuolar degradation and enhancing transfection efficiency with minimal cytotoxicity, which could facilitate diverse biotechnological applications in plant bioengineering.
Article
Nanoscience & Nanotechnology
Mika Omura, Kenta Morimoto, Yurina Araki, Hisaaki Hirose, Yoshimasa Kawaguchi, Yukiya Kitayama, Yuto Goto, Atsushi Harada, Ikuo Fujii, Tomoka Takatani-Nakase, Shiroh Futaki, Ikuhiko Nakase
Summary: A new intracellular introduction technology was developed using an inkjet device and cell-penetrating peptides to accurately deliver biofunctional cargo to cells, achieving efficient cytosolic transduction.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Pharmacology & Pharmacy
Muhammad Imran Sajid, Dindyal Mandal, Naglaa Salem El-Sayed, Sandeep Lohan, Jonathan Moreno, Rakesh Kumar Tiwari
Summary: Recent approvals of siRNA-based products have led to exploration of siRNA as a potential treatment option for cancer and other diseases. This study introduces a series of oleyl-conjugated histidine-arginine peptides as a promising nonviral siRNA delivery tool.
Review
Chemistry, Multidisciplinary
Muhammad Muzamil Khan, Nina Filipczak, Vladimir P. Torchilin
Summary: Cell penetrating peptides (CPP) have the ability to efficiently internalize across biological membranes, making them effective for delivering chemotherapeutic agents when combined with tumor targeting peptides.
JOURNAL OF CONTROLLED RELEASE
(2021)
Review
Pharmacology & Pharmacy
Shalvi Sinai Kunde, Ritushree Ghosh, Sarika Wairkar
Summary: In comparison with small molecular drugs, the use of biopharmaceuticals as therapeutics has gained popularity due to their higher specificity, selectivity and potency, as well as fewer side effects. The pulmonary route has been investigated as a potential noninvasive method for delivering biopharmaceuticals, offering higher drug concentrations and greater bioavailability than other noninvasive routes. This review focuses on the delivery of various biopharmaceuticals, including peptides, recombinant proteins, enzymes, monoclonal antibodies, and nucleic acids, via the pulmonary route, discussing their advantages and disadvantages.
DRUG DISCOVERY TODAY
(2022)
Article
Pharmacology & Pharmacy
Cristian Reboredo, Carlos J. Gonzalez-Navarro, Ana Luisa Martinez-Lopez, Cristina Martinez-Oharriz, Bruno Sarmento, Juan M. Irache
Summary: This study evaluated Zein nanoparticles, both bare and coated with poly(ethylene glycol), as oral carriers for insulin. The results showed that the poly(ethylene glycol)-coated nanoparticles had a superior effect, allowing them to diffuse through the mucus layer and reach the surface of enterocytes, where insulin could be released.
Review
Chemistry, Multidisciplinary
Gui-Mei Han, Bo Liu, De-Ming Kong, Li-Na Zhu
Summary: Drug carriers have attracted significant attention for their ability to improve drug bioavailability and minimize side effects. DNA-based nanomaterials have emerged as promising carriers due to their excellent biocompatibility, versatility, and targeting ability. This review provides an overview of recent advances in DNA-based drug carriers, highlighting targeted accumulation mechanisms and the loading, delivery, and release of various drugs.
MATERIALS CHEMISTRY FRONTIERS
(2023)
Review
Chemistry, Multidisciplinary
Shixian Lv, Meilyn Sylvestre, Alexander N. Prossnitz, Lucy F. Yang, Suzie H. Pun
Summary: Peptides as promising cancer therapeutics have shown robust antitumor efficacy, but the translation into clinical therapies is hindered by inherent limitations in their structure, hindering intracellular delivery. Strategies to engineer polymeric materials for increased peptide delivery efficiency, especially cytosolic delivery, play a crucial role in potentiating peptide-based cancer therapies. Future opportunities for peptides in cancer treatment lie in the design of polymer nanocarriers for optimized peptide delivery.
Article
Pharmacology & Pharmacy
Dagmar Yr orgeirsdottir, Jeppe Hofman Andersen, Marcus Perch-Nielsen, Laura Hyrup Moller, Freja Gronbaek-Thorsen, Hannah Gronbech Kolberg, Bente Gammelgaard, Mie Kristensen
Summary: The study compared the effect of labelling Tat and penetratin with 5(6)-carboxytetramethylrhodamine (TAMRA) and selenomethionine (MSe) on their physicochemical properties and on brain capillary endothelial cell (BCEC) models. TAMRA labelling increased the adherence and internalization of the peptides in BCECs compared to MSe labelling. However, TAMRA labelling of penetratin had a higher toxicity effect on the BCECs compared to TAMRA labelling of Tat, while MSe labelling did not affect cellular viability. Both TAMRA and MSe labelling decreased the barrier integrity of BCEC monolayers, but did not improve transport of the paracellular marker 14C-mannitol. Therefore, MSe labelling is preferred over TAMRA for quantification of peptides due to minimal alterations in physicochemical properties and effects on BCECs.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Chemistry, Physical
Xin Zhou, Anders Wilgaard Sinkjaer, Min Zhang, Henrik Dahl Pinholt, Hanne Morck Nielsen, Nikos S. Hatzakis, Marco van de Weert, Vito Fodera
Summary: Amyloid aggregation is associated with diseases and therapeutic protein formulations. Co-solutes can modulate protein stability and work as inhibitors for drug design. This study uses insulin and polysorbate 80 to analyze the heterogeneous multicomponent system at a single aggregate level and reveals the inhibition mechanism depends on growth pathways. The method is a general tool for physicochemical characterization of self-assembly reactions.
JOURNAL OF PHYSICAL CHEMISTRY LETTERS
(2023)
Article
Medicine, Research & Experimental
Ragna G. Diedrichsen, Pernille S. Tuelung, Vito Fodera, Hanne M. Nielsen
Summary: The stereochemistry of carrier peptides affects their interaction with insulin and insulin delivery. The permeation of insulin through the intestinal epithelium is influenced by the degree of insulin-carrier peptide complexation and depends on the stereochemistry of penetramax. The L-form peptides initially decrease epithelial integrity, but this effect is reversible.
MOLECULAR PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Miriam E. E. van Gent, Tom van Baaren, Sylvia N. N. Klodzinska, Muhanad Ali, Natasja Dolezal, Bjorn R. R. van Doodewaerd, Erik Bos, Amy M. M. de Waal, Roman I. I. Koning, Jan Wouter Drijfhout, Hanne Morck Nielsen, Peter H. H. Nibbering
Summary: Synthetic antibacterial and antibiofilm peptide (SAAP)-148 is an alternative treatment for chronic wound infections, but its therapeutic potential is limited due to its peptidic nature and cytotoxicity. Encapsulation of SAAP-148 in nanogels composed of OSA-modified HA overcomes these limitations. The formulated SAAP-148-loaded nanogels sustainably release the peptide and exhibit antimicrobial activity without cytotoxicity.
Article
Nanoscience & Nanotechnology
Matteo Tollemeto, Zheng Huang, Jorn B. Christensen, Hanne Morck Nielsen, Stine Ronholt
Summary: Biological drugs are increasingly important for the treatment of diseases such as diabetes, cancer, and obesity. This project explores the potential of using mucoadhesive delivery systems based on dendron-coated mesoporous silica nanoparticles for oral delivery of biological drugs. The study focuses on the interaction between dendrons and mucin, and successfully conjugates dendrons onto mesoporous silica nanoparticles. The interaction between the nanoparticles and mucin or intestinal mucus is investigated, providing knowledge for the development of mucoadhesive nanoformulations for oral delivery of biopharmaceuticals.
ACS APPLIED MATERIALS & INTERFACES
(2023)
Article
Biochemical Research Methods
Shunliang Wu, Mads Ostergaard, Freja Fredholt, Niels Johan Christensen, Kasper K. Sorensen, Narendra K. Mishra, Hanne M. Nielsen, Knud J. Jensen
Summary: Chemical modification of peptides and proteins, such as PEGylation and lipidation, can create new conjugates with different properties. However, these conjugates are often not responsive to stimuli. This study reports the Ca2+-responsive properties of conjugates of oligogalacturonic acids (OGAs), derived from plant pectin. The self-assembly of OGA conjugates was studied and found to depend on OGA sequence length, as well as Zn2+ and Ca2+ concentrations.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Chemistry, Applied
Mai Bay Stie, Heidi Oblom, Anders Christian Norgaard Hansen, Jette Jacobsen, Ioannis S. Chronakis, Jukka Rantanen, Hanne Morck Nielsen, Natalja Genina
Summary: The study designed a multi-layered nanofiber-on-foam-on-film (NFF) drug delivery system with mucoadhesive properties and saliva-repelling ability, which improved drug absorption and permeability through oral mucosa. This system has great potential for non-invasive drug administration.
CARBOHYDRATE POLYMERS
(2023)
Correction
Chemistry, Physical
Xin Zhou, Dirk Fennema Galparsoro, Anders Ostergaard Madsen, Valeria Vetri, Marco van de Weert, Hanne Morck Nielsen, Vito Fodera
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Instruments & Instrumentation
Janni Stovring Mortensen, Duc Ninh Nguyen, Hanne Morck Nielsen, Stine Ronholt
Summary: Early intervention and short-duration antibiotics treatment in premature infants can reduce the incidence of necrotizing enterocolitis (NEC), but it is unclear how antibiotics exposure and route of administration affect the disease risk. This study investigated the effects of ampicillin and gentamicin administered through parenteral or a combination of enteral and parenteral routes on the barrier properties of intestinal mucosa and mucus in preterm piglets. Results showed that permeation through mucosa and mucus was reduced in parenterally treated piglets compared to untreated piglets, while treatments with both routes showed similar permeation to untreated piglets. Rheological measurements also showed changes in mucus properties.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Ditlev Birch, Edward J. Sayers, Malene V. Christensen, Arwyn T. Jones, Henrik Franzyk, Hanne M. Nielsen
Summary: This study compared the membrane association, cellular uptake, and delivery capacity of all-l and all-d enantiomers of penetratin in different cell models and cargos. The results showed that d-PEN had tighter membrane binding and was superior in delivering hydrophilic peptide cargoes across the Caco-2 epithelium compared to l-PEN. However, there was no enhanced delivery of the hydrophobic cyclosporin, and both enantiomers had similar intracellular insulin uptake.
Article
Chemistry, Physical
Ragna Guldsmed Diedrichsen, Valeria Vetri, Sylvain Prevost, Vito Fodera, Hanne Morck Nielsen
Summary: The cell-penetrating peptide penetratin and its analogues shuffle and penetramax have been investigated for their potential as carrier peptides for oral drug delivery. Through advanced biophysical techniques, it was found that these peptides induced liposome clustering, with distinctively different types of membrane interactions observed. Furthermore, these interactions did not disrupt the liposomes, making them advantageous for drug delivery applications. This detailed insight into peptide-membrane interactions is crucial for understanding the mechanism of peptide-based excipients and the influence of peptide sequence modifications.
JOURNAL OF COLLOID AND INTERFACE SCIENCE
(2023)
Article
Nanoscience & Nanotechnology
Miriam E. van Gent, Sylvia N. Kiodsinska, Maureen Severin, Muhanad Ali, Bjorn R. van Doodewaerd, Erik Bos, Roman I. Koning, Jan Wouter Drijfhout, Hanne M. Nielsen, Peter H. Nibbering
Summary: Hyaluronic acid-based nanogels were used to encapsulate the antimicrobial peptide Ab-Cath, overcoming its limitations and reducing its cytotoxic effects. The nanogels effectively killed antibiotic-resistant bacteria and eliminated bacteria on human skin. This study highlights the potential of nanogels to enhance the selectivity of antimicrobial peptides.
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2023)
Article
Neurosciences
Burak Ozguer, Elena Puris, Andreas Brachner, Antje Appelt-Menzel, Sabrina Oerter, Viktor Balzer, Mikkel Roland Holst, Rasmus Folmann Christiansen, Kathrine Hyldig, Stephen T. Buckley, Mie Kristensen, Seppo Auriola, Allan Jensen, Gert Fricker, Morten Schallburg Nielsen, Winfried Neuhaus, Birger Brodin
Summary: In this study, a tight monolayer blood-brain barrier (BBB) model was established using human induced pluripotent stem cell (hiPSC)-derived BCECs from the hIPSC line SBAD0201. The model proved to be useful for studying the transport mediated by GLUT-1, LAT-1, and LRP-1 across the BBB. However, the model did not express functional P-gp and is not suitable for drug efflux P-gp related studies.
FLUIDS AND BARRIERS OF THE CNS
(2023)
Article
Pharmacology & Pharmacy
Miriam E. van Gent, Sylvia N. Klodzinska, Jan Wouter Drijfhout, Hanne M. Nielsen, Peter H. Nibbering
Summary: This study evaluated the encapsulation of two antimicrobial peptides (AMPs) into nanogels to improve their selectivity index. The nanogels showed similar activity to AMP solutions against antimicrobial resistant bacteria and reduced cytotoxicity towards human cells, thereby increasing their potential as therapeutics.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Meeting Abstract
Biophysics
Soren S. R. Bohr, Sarah Streck, Henrik Pinholt, Feng Wan, Arlene McDowell, Hanne M. Nielsen, Nikos S. Hatzakis
BIOPHYSICAL JOURNAL
(2022)