Review
Pharmacology & Pharmacy
Yingke Liu, Zhihe Zhao, Man Li
Summary: Cell penetrating peptides (CPPs), a class of short peptides capable of translocating drugs across cell membranes, have shown significant potential in drug delivery, particularly in the treatment of cancer, myocardial ischemia, ocular posterior segment disorders, etc. Recent research has focused on CPP-functionalized nano-drug delivery systems, highlighting their promising clinical translation.
ASIAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Multidisciplinary
Xuan Yang, Xiaowei Wen, Jie Dai, Yanming Chen, Wanchuan Ding, Jun Wang, Xiang Gu, Xuejin Zhang, Jin Chen, Roy L. Sutliff, Steven R. Emory, Gang Ruan
Summary: This study investigates nanoparticle transport in hard-to-transfect cells using single-particle motion analysis, cell biology studies, and mathematical modeling. The researchers find significant differences in the transport of nanoparticles in bone marrow-derived mesenchymal stem cells (BMSCs) compared to HeLa cells. They also discover that BMSCs use different biological pathways for cellular uptake, vesicular transport, and exocytosis of nanoparticles compared to HeLa cells. A reaction-diffusion-advection model is used to mathematically integrate the steps of cellular transport and predict nanoparticle delivery in BMSCs. This work provides important insights into nanoparticle transport in hard-to-transfect cells and can guide the design of tailored nanoparticle-based delivery systems.
Review
Biochemistry & Molecular Biology
Zhe Sun, Jinhai Huang, Zvi Fishelson, Chenhui Wang, Sihe Zhang
Summary: Cell-penetrating peptides (CPPs) are extensively studied for their excellent delivery performance and promise for delivering different types of drugs. In this review, the development process of CPPs is reviewed, and the composition and classification of CPP-based delivery systems, cellular uptake mechanisms, influencing factors, and biological barriers are summarized. Optimization routes for CPP-based macromolecular drug delivery are also summarized, including enhanced endosomal escape, prolonged half-life in blood, improved targeting efficiency, and stimuli-responsive design. The necessary conditions for a successful CPP-based delivery system are extracted from concluding the clinical trials. This review provides the latest framework and optimized strategies for CPP-based delivery of macromolecular drugs to improve delivery efficiency.
Article
Pharmacology & Pharmacy
Mo'ath Yousef, Ildiko Szabo, Jozsef Muranyi, Francoise Illien, Dora Soltesz, Csaba Bato, Gabriella Toth, Gyula Batta, Peter Nagy, Sandrine Sagan, Zoltan Banoczi
Summary: This study demonstrates the preparation and investigation of efficient cell-penetrating peptides (CPPs) and explores the possibility of using unnatural aromatic amino acids to mimic the properties of tryptophan. These highly active CPPs have been successful in delivering antitumor drugs into specific cell lines.
Article
Pharmacology & Pharmacy
Emma M. McErlean, Cian M. McCrudden, John W. McBride, Grace Cole, Vicky L. Kett, Tracy Robson, Nicholas J. Dunne, Helen O. McCarthy
Summary: RALA, a cationic amphipathic peptide, has shown promise as an efficient nucleic acid delivery system. Rational peptide design was used to create six amphipathic peptides with potential for nucleic acid delivery, but not all were successful in transfection, highlighting the importance of peptide design for cellular uptake and endosomal escape. Pep2 showed similar characteristics to RALA but had issues with toxicity and lack of pH-responsiveness, making RALA the superior choice for non-toxic gene delivery.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Review
Biotechnology & Applied Microbiology
Ying Zhang, Pan Guo, Zhe Ma, Peng Lu, Dereje Kebebe, Zhidong Liu
Summary: Despite the advancements in nanomedicine and the extension of human lifespan, there has been a significant increase in the incidence of central nervous system (CNS) diseases. The blood-brain barrier poses a challenge for delivering therapeutic drugs to the brain. Cell penetrating peptides (CPPs) offer a potential strategy for overcoming this barrier and providing a scientific basis for treating CNS diseases.
JOURNAL OF NANOBIOTECHNOLOGY
(2021)
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)
Article
Medicine, Research & Experimental
Nasim Shadmani, Pooyan Makvandi, Maliheh Parsa, Amir Azadi, Keivan Nedaei, Negin Mozafari, Narges Poursina, Virgilio Mattoli, Franklin R. Tay, Aziz Maleki, Mehrdad Hamidi
Summary: The blood-brain barrier is a protective barrier that prevents potential damages to the brain from chemicals in the bloodstream. This study showed that modifying mesoporous silica nanoparticles with TAT peptide improves the penetration of methotrexate into the brain. The results suggest that this nanosystem could be a promising drug carrier to overcome the blood-brain barrier and deliver methotrexate into the brain.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Chi Huang, Zhenyu Han, Michael Evangelopoulos, Chad A. Mirkin
Summary: This study presents the design and evaluation of a new type of CRISPR SNA that has the potential to broaden the scope and impact of genome editing. By utilizing spherical nucleic acid structures, this SNA efficiently delivers editing components to cell membranes and tissues. The modified Cas9 protein core enhances cellular uptake, and additional modifications facilitate endosomal escape and maximize nuclear localization and editing efficiency.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Review
Pharmacology & Pharmacy
Ildiko Szabo, Mo'ath Yousef, Dora Soltesz, Csaba Bato, Gabor Mezo, Zoltan Banoczi
Summary: Cell-penetrating peptides (CPPs) are a diverse group of molecules with promising potential for transporting compounds into cells, but face challenges such as non-specific internalization and rapid elimination from the body. Despite growing understanding of the mechanisms involved, predicting and designing the cell-penetrating properties of CPPs remains a complex task. Efforts are being made to modify well-known CPPs in order to overcome their limitations and enhance their internalization capabilities and penetration mechanisms.
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)
Article
Cell Biology
Hannah C. Hymel, Alireza Rahnama, Olivia M. Sanchez, Dong Liu, Ted J. Gauthier, Adam T. Melvin
Summary: Cell-penetrating peptides (CPPs) are powerful tools for delivering impermeable cargoes into cells. This study found that the net charge of the cargo affects the uptake of CPP/cargo complexes, with positively charged cargoes enhancing uptake and neutral/negatively charged cargoes diminishing uptake. The length of the cargo did not significantly affect uptake.
Article
Pharmacology & Pharmacy
Baohuan Wu, Mengshun Li, Keke Li, Wei Hong, Qingzhi Lv, Youjie Li, Shuyang Xie, Jingtian Han, Baocheng Tian
Summary: This study successfully designed a TAT-Lip system that can promote corneal drug delivery, and its effectiveness was confirmed through in vitro and in vivo experiments, effectively reducing drug loss rate and demonstrating good anti-inflammatory effects in animal models.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Yoshiyuki Hakata, Kazuma Yamashita, Sonoko Hashimoto, Takashi Ohtsuki, Masaaki Miyazawa, Mizuki Kitamatsu
Summary: The connection between a functional peptide and a cell-penetrating peptide (CPP) using a heterodimeric coiled-coil as a molecular zipper can enhance the intracellular delivery and activity of the functional peptide. In this study, we investigated the optimal length of the K/E zipper for effective intracellular delivery and autophagy induction by conjugating an autophagy-inducing peptide (AIP) with CPP via heterodimeric coiled-coils consisting of 1 to 4 repeating units (K/E zipper; AIP-Kn and En-CPP). The results showed that K/E zippers with n = 3 and 4 formed stable hybrids and effectively induced autophagy, with the former being more intensive.
Article
Medicine, Research & Experimental
Marina Buyanova, Ashweta Sahni, Rui Yang, Amar Sarkar, Heba Salim, Dehua Pei
Summary: Cyclic cell-penetrating peptide 12 (CPP12) is highly efficient at delivering cargo molecules into mammalian cells. However, its efficiency is reduced at lower concentrations or in the presence of serum proteins. In this study, CPP12 analogs were prepared with varying hydrophobicity and evaluated for cellular entry. CPP12-2, with a substitution of L-3-benzothienylalanine (Bta) for L-2-naphthylalanine (Nal), showed up to 3.8-fold higher efficiency, especially at low concentrations, due to improved endosomal escape efficiency.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Maruthi Prasanna, Daphnee Soulard, Emilie Camberlein, Nicolas Ruffier, Annie Lambert, Francois Trottein, Noemi Csaba, Cyrille Grandjean
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2019)
Review
Polymer Science
Wei-Hsin Hsu, Noemi Csaba, Cameron Alexander, Marcos Garcia-Fuentes
JOURNAL OF APPLIED POLYMER SCIENCE
(2020)
Article
Pharmacology & Pharmacy
Peter Gieszinger, Noemi Stefania Csaba, Marcos Garcia-Fuentes, Maruthi Prasanna, Robert Gaspar, Anita Sztojkov-Ivanov, Eszter Ducza, Arpad Marki, Tamas Janaky, Gabor Kecskemeti, Gabor Katona, Piroska Szabo-Revesz, Rita Ambrus
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2020)
Article
Instruments & Instrumentation
Sandra Robla, Maruthi Prasanna, Ruben Varela-Calvino, Cyrille Grandjean, Noemi Csaba
Summary: Chitosan-based nanosystems conjugated with Streptococcus pneumoniae cell membrane protein PsaA have shown promising results in enhancing antigen uptake by immune cells and activating specific T cells, thus generating an adaptive immune response against pneumococcus. The designed nanocapsules, with good stability and positive charge, displayed increased association rates with PsaA compared to non-covalent conjugation, and exhibited no cytotoxic effects at certain concentrations in cell culture media. Furthermore, the nanocapsules were shown to activate CD4 and CD8 T lymphocytes, as well as promote the maturation of immature dendritic cells, suggesting their potential as a nasal vaccine delivery method.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Article
Polymer Science
Jose Manuel Ageitos, Sandra Robla, Lorena Valverde-Fraga, Marcos Garcia-Fuentes, Noemi Csaba
Summary: The study introduces a simplified method to produce stable and pristine hollow pollen microcapsules, with a complete physicochemical and morphological characterization of the intermediate and final products. The optimized procedure has been validated for different pollen samples, showing potential for pharmaceutical applications as a drug delivery platform.
Article
Pharmacology & Pharmacy
Mahwash Mukhtar, Noemi Csaba, Sandra Robla, Ruben Varela-Calvino, Attila Nagy, Katalin Burian, David Kokai, Rita Ambrus
Summary: A nano-DPI system was developed by combining isoniazid (INH) with mannosylated chitosan (MC) and hyaluronic acid (HA), and preparing dry powder through an ionic gelation method. The nanoparticles showed no significant toxicity to cells, good compatibility with red blood cells, and activated T-cell response. Moreover, the nanoparticles were translocated in macrophages.
Article
Chemistry, Multidisciplinary
Patrik Lundquist, Georgiy Khodus, Zhigao Niu, Lungile Nomcebo Thwala, Fiona McCartney, Ivailo Simoff, Ellen Andersson, Ana Beloqui, Aloise Mabondzo, Sandra Robla, Dominic-Luc Webb, Per M. Hellstroem, asa Keita, Eduardo Sima, Noemi Csaba, Magnus Sundbom, Veronique Preat, David J. Brayden, Maria Jose Alonso, Per Artursson
Summary: Peptide drugs are not orally bioavailable due to their poor stability and permeability, but nanoparticle formulations may provide a solution. In this study, the absorption mechanisms of four insulin-loaded arginine-rich nanoparticles were investigated. One nanoparticle showed significant uptake and is proposed for further investigation for local delivery.
Article
Pharmacology & Pharmacy
Sandra Robla, Ruben Varela Calvino, Rita Ambrus, Noemi Csaba
Summary: To address the side effects and resistance issues of oral antibiotic therapy for respiratory diseases, inhalable formulations using biomaterials like protamine were developed to enhance therapeutic effect. Rifabutin-loaded protamine nanocapsules were prepared and evaluated for their physico-chemical characteristics, dissolution, permeability, stability, cytotoxicity, hemocompatibility, internalization, and aerodynamic properties. The nanocapsules showed good stability as suspension, both in storage and in biological media, as well as in the form of dry powder after lyophilization with mannitol. They exhibited excellent safety profile, cellular uptake, and compatibility with red blood cells. Furthermore, the aerodynamic evaluation demonstrated suitable particle size for pulmonary delivery of therapeutics, with a fine particle fraction deposition of up to 30% and a mass median aerodynamic diameter of about 5 µm.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemical Research Methods
Maruthi Prasanna, Ruben Varela Calvino, Annie Lambert, Maria Arista Romero, Sylvia Pujals, Francois Trottein, Emilie Camberlein, Cyrille Grandjean, Noemi Csaba
Summary: This study demonstrates the potential of chitosan-based nanovaccines for efficient delivery of glycoconjugate antigens. Encapsulated glycoconjugates showed enhanced uptake by cells and better immunostimulatory properties compared to naked antigens. The study also showed a 100-fold increase in IgG response with the encapsulated glycoconjugate compared to the nonencapsulated group in mice.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Lorena Valverde-Fraga, Razan Haddad, Nasr Alrabadi, Sandra Sanchez, Carmen Remunan-Lopez, Noemi Csaba
Summary: This study aims to develop a nanosystem for improved delivery of antibiotics for pulmonary delivery. The nanocarrier, consisting of a chitosan shell and a lipid core, showed efficient antimicrobial effects against Mycobacterium tuberculosis and safe internalization in different cell models. This research provides a promising approach for the treatment of tuberculosis.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Biochemical Research Methods
Maruthi Prasanna, Ruben Varela Calvino, Annie Lambert, Maria Arista Romero, Sylvia Pujals, Francois Trottein, Emilie Camberlein, Cyrille Grandjean, Noemi Csaba
Summary: This study demonstrates the potential of chitosan-based nanovaccine for efficient delivery of glycoconjugate antigens. The encapsulation of the glycoconjugate using chitosan nanoparticles (CNPs) enhanced its immunogenicity and resulted in a significantly higher immune response compared to the nonencapsulated glycoconjugate. These findings suggest that CNPs could be a promising delivery system for pneumococcal conjugate vaccines.
BIOCONJUGATE CHEMISTRY
(2023)
Article
Pharmacology & Pharmacy
Sergio del Rio-Sancho, Diego Pan Delgado, German F. de la Fuente, Tomas Garcia-Caballero, Antonio Taboada-Suarez, Noemi Csaba, Carmen Bao-Varela, Maria Jose Alonso
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2020)