Search Our Scientific Publications & Authors

Pharmaceutics 2021 Mar 22;13(3). Epub 2021 Mar 22.

Grupo de Diseño de Productos y Procesos (GDPP), Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá 111711, Colombia.

Gene therapy has been used as a potential approach to address the diagnosis and treatment of genetic diseases and inherited disorders. In this line, non-viral systems have been exploited as promising alternatives for delivering therapeutic transgenes and proteins. In this review, we explored how biological barriers are effectively overcome by non-viral systems, usually nanoparticles, to reach an efficient delivery of cargoes. Read More

Nanomaterials (Basel) 2021 Mar 23;11(3). Epub 2021 Mar 23.

Department of Surgery, University of Tennessee Graduate School of Medicine, 1924 Alcoa Highway Box U-11, Knoxville, TN 37920, USA.

Lipid nanoparticles have become increasingly popular delivery platforms in the field of gene therapy, but bench-to-bedside success has been limited. Many liposomal gene vectors are comprised of synthetic cationic lipids, which are associated with lipid-induced cytotoxicity and immunogenicity. Natural, non-cationic PEGylated liposomes (PLPs) demonstrate favorable biocompatibility profiles but are not considered viable gene delivery vehicles due to inefficient nucleic acid loading and reduced cellular uptake. Read More

Int J Mol Sci 2021 Mar 13;22(6). Epub 2021 Mar 13.

Department of General Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, Poland.

Carriers of genetic material are divided into vectors of viral and non-viral origin. Viral carriers are already successfully used in experimental gene therapies, but despite advantages such as their high transfection efficiency and the wide knowledge of their practical potential, the remaining disadvantages, namely, their low capacity and complex manufacturing process, based on biological systems, are major limitations prior to their broad implementation in the clinical setting. The application of non-viral carriers in gene therapy is one of the available approaches. Read More

Pharmaceutics 2021 Mar 27;13(4). Epub 2021 Mar 27.

School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool L3 3AF, UK.

The development of vaccines is one of the most significant medical accomplishments which has helped to eradicate a large number of diseases. It has undergone an evolutionary process from live attenuated pathogen vaccine to killed whole organisms or inactivated toxins (toxoids), each of them having its own advantages and disadvantages. The crucial parameters in vaccination are the generation of memory response and protection against infection, while an important aspect is the effective delivery of antigen in an intelligent manner to evoke a robust immune response. Read More

Int J Pharm 2021 Mar 26:120529. Epub 2021 Mar 26.

Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan. Electronic address:

Nucleic acid-based therapy with plasmid DNA (pDNA) and small interfering RNA (siRNA) have received recent attention for their ability to modulate the cellular expression of genes and proteins. Polyethylene glycol-modified (PEGylated) cationic nanoparticles have been used as non-viral vectors for the in vivo delivery of these nucleic acids. We have reported that PEGylated cationic liposomes (PCL) including pDNA or siRNA induce anti-PEG antibodies upon repeated intravenous injection, leading to the formation of immune complexes and enhanced clearance from the blood of subsequent doses. Read More

ACS Appl Nano Mater 2021 Jan 21;4(1):167-181. Epub 2020 Dec 21.

Regenerative Medicine & Cellular Therapies Division, The University of Nottingham Biodiscovery Institute (BDI), School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, U.K.

Non-viral delivery systems are generally of low efficiency, which limits their use in gene therapy and editing applications. We previously developed a technology termed glycosaminoglycan (GAG)-binding enhanced transduction (GET) to efficiently deliver a variety of cargos intracellularly; our system employs GAG-binding peptides, which promote cell targeting, and cell penetrating peptides (CPPs), which enhance endocytotic cell internalization. Herein, we describe a further modification by combining gene delivery and magnetic targeting with the GET technology. Read More

J Nanobiotechnology 2021 Mar 8;19(1):71. Epub 2021 Mar 8.

Department of Histopathology and Morbid Anatomy, Sir Patrick Dun Translational Research Lab, St. James's Hospital, Dublin, Ireland.

Background: siRNAs hold a great potential for cancer therapy, however, poor stability in body fluids and low cellular uptake limit their use in the clinic. To enhance the bioavailability of siRNAs in tumors, novel, safe, and effective carriers are needed.

Results: Here, we developed cationic solid lipid nanoparticles (cSLNs) to carry siRNAs targeting EphA2 receptor tyrosine kinase (siEphA2), which is overexpressed in many solid tumors including prostate cancer. Read More

Avicenna J Med Biotechnol 2021 Jan-Mar;13(1):2-8

Department of Advanced Sciences and Technologies, Faculty of Medicine, North Khorasan University of Medical Sciences, Bojnurd, Iran.

Background: The application of non-viral systems for delivering genes to cells is becoming a very interesting issue, especially in the treatment of neoplasms such as Breast Cancer (BC). Polymer-based non-viral systems are safe and feasible gene carriers to be used in targeted cancer therapy. gene encodes a transcription factor and is overexpressed in some cancers. Read More

J Control Release 2021 Mar 4;332:346-366. Epub 2021 Mar 4.

Laboratoire de Chimie de Coordination du CNRS, 205 route de Narbonne, 31077 Toulouse Cedex 4, France; Université Toulouse 118 route de Narbonne, 31077 Toulouse Cedex 4, France. Electronic address:

Nanomedicine represents a very significant contribution in current cancer treatment; in addition to surgical intervention, radiation and chemotherapeutic agents that unfortunately also kill healthy cells, inducing highly deleterious and often life-threatening side effects in the patient. Of the numerous nanoparticles used against cancer, gold nanoparticles had been developed for therapeutic applications. Inter alia, a large variety of dendrimers, i. Read More

Int J Mol Sci 2021 Feb 26;22(5). Epub 2021 Feb 26.

UCL Institute of Ophthalmology, London EC1V 9EL, UK.

Inherited retinal diseases (IRDs) are a heterogeneous group of disorders causing progressive loss of vision, affecting approximately one in 1000 people worldwide. Gene augmentation therapy, which typically involves using adeno-associated viral vectors for delivery of healthy gene copies to affected tissues, has shown great promise as a strategy for the treatment of IRDs. However, the use of viruses is associated with several limitations, including harmful immune responses, genome integration, and limited gene carrying capacity. Read More

Rep Biochem Mol Biol 2020 Oct;9(3):297-308

Nano biotechnology Department, Faculty of Bioscience, Tarbiat Modares University, Tehran, Iran.

Background: One of the major challenges in gene therapy is producing gene carriers that possess high transfection efficiency and low cytotoxicity (1). To achieve this purpose, crystal nanocellulose (CNC) -based nanoparticles grafted with polyethylenimine (PEI) have been developed as an alternative to traditional viral vectors to eliminate potential toxicity and immunogenicity.

Methods: In this study, CNC-PEI10kDa (CNCP) nanoparticles were synthetized and their transfection efficiency was evaluated and compared with linear cationic PEI10kDa (PEI) polymer in HEK293T (HEK) cells. Read More

J Control Release 2021 Feb 17;332:210-224. Epub 2021 Feb 17.

School of Pharmacy, University College London, London, UK. Electronic address:

Short dwell-time and poor penetration of the bladder permeability barrier (BPB) are the main obstacles to intravesical treatments for bladder diseases, and is evidenced by the lack of such therapeutic options on the market. Herein, we demonstrate that by finely tuning the molecular weight of our cationic polymer mucoadhesive nanoparticles, we enhanced our gene transfer, leading to improved adherence and penetrance through the BPB in a safe and efficient manner. Specifically, increasing the polymer molecular weight from 45 kDa to 83 kDa enhanced luciferase plasmid transfer to the healthy murine bladder, leading to 1. Read More

Biomater Sci 2021 Feb 15. Epub 2021 Feb 15.

Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life Sciences Building, Oregon State University, Portland, Oregon 97201, USA and Department of Biomedical Engineering, Robertson Life Sciences Building, Oregon Health & Science University, Portland, Oregon 97201, USA. and Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon 97239, USA.

Lipid-based nanoparticles (LNPs) for the delivery of mRNA have jumped to the forefront of non-viral gene delivery. Despite this exciting development, poor endosomal escape after LNP cell entry remains an unsolved, rate-limiting bottleneck. Here we report the use of a galectin 8-GFP (Gal8-GFP) cell reporter system to visualize the endosomal escape capabilities of LNP-encapsulated mRNA. Read More

Pharmaceutics 2021 Feb 2;13(2). Epub 2021 Feb 2.

Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia.

There has been increased interest in the development of RNA-based vaccines for protection against various infectious diseases and also for cancer immunotherapies. Rapid and cost-effective manufacturing methods in addition to potent immune responses observed in preclinical and clinical studies have made mRNA-based vaccines promising alternatives to conventional vaccine technologies. However, efficient delivery of these vaccines requires that the mRNA be protected against extracellular degradation. Read More

Vaccines (Basel) 2021 Jan 28;9(2). Epub 2021 Jan 28.

Precision NanoSystems Inc., Vancouver, BC V6P 6T7, Canada.

This review will explore the four major pillars required for design and development of an saRNA vaccine: Antigen design, vector design, non-viral delivery systems, and manufacturing (both saRNA and lipid nanoparticles (LNP)). We report on the major innovations, preclinical and clinical data reported in the last five years and will discuss future prospects. Read More

Int J Pharm 2021 Mar 27;596:120223. Epub 2021 Jan 27.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; School of Chemical Sciences, Dublin City University, Dublin 9, Ireland, UK.

RALA is a cationic amphipathic peptide which has shown great promise as an efficient, multifunctional delivery system for the delivery of nucleic acids. Rational peptide design was utilised in this study to understand the essential amino acids required for delivery and if any improvements to the RALA peptide could be made. Six amphipathic peptides were synthesised with strategic sequences and amino acid substitutions to reduce peptide sequence, while maintaining the functional characteristics of RALA including amphipathicity, alpha-helicity and pH responsiveness for endosomal escape. Read More

Bioengineering (Basel) 2021 Jan 20;8(2). Epub 2021 Jan 20.

Department of Biomedical Engineering and Chemical Engineering, University of Texas at San Antonio, One UTSA Circle, San Antonio, TX 78249, USA.

The administration of gene-editing tools has been proposed as a promising therapeutic approach for correcting mutations that cause diseases. Gene-editing tools, composed of relatively large plasmid DNA constructs that often need to be co-delivered with a guiding protein, are unable to spontaneously penetrate mammalian cells. Although viral vectors facilitate DNA delivery, they are restricted by the size of the plasmid to carry. Read More

Expert Opin Drug Deliv 2021 Jan 22:1-18. Epub 2021 Jan 22.

The Novel Drug and Vaccine Delivery Systems Facility, Department of Chemistry and Biochemistry, Laurentian University , Sudbury, Ontario, Canada.

: Cystic fibrosis (CF), is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene and affects thousands of people throughout the world. Lung disease is the leading cause of death in CF patients. Despite the advances in treatments, the management of CF mainly targets symptoms. Read More

Curr Gene Ther 2020 Dec 30. Epub 2020 Dec 30.

School of Pharmaceutical Science of Sao Paulo State University (UNESP), Araraquara, Sao Paulo,. Brazil.

Gliomas are primary brain tumors originating from glial cells, representing 30% of all Central Nervous System (CNS) neoplasia. Among them, the astrocytoma grade IV (glioblastoma multiforme) is the most common presenting an invasive and aggressive profile, with an estimated life expectancy about 15 months after diagnosis even after treatment with radiation, surgical resection, and chemotherapy. This poor prognostic is related to the presence of the blood-brain barrier (BBB) and multidrug resistance mechanisms that avoid the uptake and retention of chemotherapeutics inside the brain. Read More

Methods 2020 Dec 31. Epub 2020 Dec 31.

Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, Portugal; Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal. Electronic address:

RNA-based therapies are highly selective and powerful regulators of biological functions. Non-viral vectors such as nanoparticles (NPs) are very promising formulations for the delivery of RNA-based therapies but their cell targeting, cell internalization and endolysomal escape capacity is rather limited. Here, we present a methodology that combines high-throughput synthesis of light-triggerable NPs and a high-content imaging screening to identify NPs capable of efficiently delivering different type of RNAs. Read More

J Control Release 2021 Feb 21;330:329-340. Epub 2020 Dec 21.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106, United States of America. Electronic address:

It is still a challenge to develop gene replacement therapy for retinal disorders caused by mutations in large genes, such as Stargardt disease (STGD). STGD is caused by mutations in ABCA4 gene. Previously, we have developed an effective non-viral gene therapy using self-assembled nanoparticles of a multifunctional pH-sensitive amino lipid ECO and a therapeutic ABCA4 plasmid containing rhodopsin promoter (pRHO-ABCA4). Read More

Pharmaceutics 2020 Dec 16;12(12). Epub 2020 Dec 16.

Tissue Engineering Research Group, Department of Anatomy and Regenerative Medicine, Royal College of Surgeons in Ireland (RCSI), 123 St Stephen's Green, D02 YN77 Dublin, Ireland.

Nonviral vectors offer a safe alternative to viral vectors for gene therapy applications, albeit typically exhibiting lower transfection efficiencies. As a result, there remains a significant need for the development of a nonviral delivery system with low cytotoxicity and high transfection efficacy as a tool for safe and transient gene delivery. This study assesses MgAl-NO layered double hydroxide (LDH) as a nonviral vector to deliver nucleic acids (pDNA, miRNA and siRNA) to mesenchymal stromal cells (MSCs) in 2D culture and using a 3D tissue engineering scaffold approach. Read More

Eur J Pharm Biopharm 2021 Jan 15;158:359-364. Epub 2020 Dec 15.

Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians Universität München, 81377 Munich, Germany. Electronic address:

With the approval of the first siRNA-based drugs, non-viral siRNA delivery has gained special interest in industry and academia in the last two years. For non-viral delivery, positively charged lipid and polymer formulations play a central role in research and development. However, nanoparticle size characterization, particularly of polydisperse formulations, can be very challenging. Read More

J Control Release 2021 Feb 14;330:61-71. Epub 2020 Dec 14.

Laboratory for Molecular Design of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Hokkaido, Japan. Electronic address:

The clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) system has considerable therapeutic potential for use in treating a wide range of intractable genetic and infectious diseases including hepatitis B virus (HBV) infections. While non-viral delivery technologies for the CRISPR/Cas system are expected to have clinical applications, difficulties associated with the clinically relevant synthesis of formulations and the poor efficiency of delivery severely hinder therapeutic genome editing. We report herein on the production of a lipid nanoparticle (LNP)-based CRISPR/Cas ribonucleoprotein (RNP) delivery nanoplatform synthesized using a clinically relevant mixer-equipped microfluidic device. Read More

Aging (Albany NY) 2020 11 27;12(22):22527-22537. Epub 2020 Nov 27.

Department of Bone and Joint Surgery, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong Province, China.

Aging-related inflammation is tightly linked with the development of osteoarthritis (OA). As the pro-inflammatory cytokine, IL-1β has been associated with physical dysfunction and frailty. It is still elusive whether and how IL-1β blockade improves the outcome of OA. Read More

PLoS One 2020 1;15(12):e0242867. Epub 2020 Dec 1.

ANGANY Inc, Québec, Québec, Canada.

Allergen immunotherapy (AIT) is the only disease-modifying treatment with evidence for sustained efficacy. However, it is poorly developed compared to symptomatic drugs. The main reasons come from treatment duration implying monthly injections during 3 to 5 years or daily sublingual use, and the risk of allergic side-effects. Read More

Sci Rep 2020 11 26;10(1):20672. Epub 2020 Nov 26.

Department of Pharmaceutical Nanotechnology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.

Evaluation of the effect of different parameters for designing a non-viral vector in gene delivery systems has great importance. In this manner, 2D crystals, precisely layered double hydroxides, have attracted the attention of scientists due to their significant adjustability and low-toxicity and low-cost preparation procedure. In this work, the relationship between different physicochemical properties of LDH, including pH, size, zeta potential, and synthesis procedure, was investigated and optimized for CRISPR/Cas9 delivery and reverse fluorescence response to the EGFP. Read More

ChemistryOpen 2020 Nov 16;9(11):1181-1189. Epub 2020 Nov 16.

Yıldız Technical University, Molecular Biology and Genetic Department, Istanbul, 34220.

Induced pluripotent stem cells (IPSC) are preferred as an alternative source for regenerative medicine, disease modeling, and drug screening due to their unique properties. As seen from the previous studies in the literature, most of the vector systems to transfer reprogramming factors are viral-based and have some well-known limitations. This study aims to develop a non-viral vector system for the transfection of reprogramming factors. Read More

Sci Rep 2020 11 24;10(1):20486. Epub 2020 Nov 24.

National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK.

To overcome the scarcity of primary human alveolar epithelial cells for lung research, and the limitations of current cell lines to recapitulate the phenotype, functional and molecular characteristics of the healthy human alveolar epithelium, we have developed a new method to immortalise primary human alveolar epithelial lung cells using a non-viral vector to transfect the telomerase catalytic subunit (hTERT) and the simian virus 40 large-tumour antigen (SV40). Twelve strains of immortalised cells (ICs) were generated and characterised using molecular, immunochemical and morphological techniques. Cell proliferation and sensitivity to polystyrene nanoparticles (PS) were evaluated. Read More

J Control Release 2021 Feb 21;330:1288-1299. Epub 2020 Nov 21.

School of Pharmacy, Queen's University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; School of Chemical Sciences, Dublin City University, Dublin 9, Ireland. Electronic address:

The design of a non-viral gene delivery system that can release a functional nucleic acid at the intracellular destination site is an exciting but also challenging proposition. The ideal gene delivery vector must be non-toxic, non-immunogenic, overcome extra- and intra-cellular barriers, protect the nucleic acid cargo from degradation with stability over a range of temperatures. A new 15 amino acid linear peptide termed CHAT was designed in this study with the goal of delivering DNA with high efficiency into cells in vitro and tissues in vivo. Read More