scholarly journals Stable and efficient generation of poly(β-amino ester)s for RNAi delivery

2018 ◽  
Vol 3 (4) ◽  
pp. 677-689 ◽  
Author(s):  
P. Dosta ◽  
V. Ramos ◽  
S. Borrós
Keyword(s):  
Transfection Efficiency ◽  
Scale Up ◽  
Delivery Systems ◽  
Amino Ester ◽  
Cationic Polymers ◽  
Efficient Generation

Cationic polymers are promising delivery systems for RNAi due to their ease of manipulation, scale-up conditions and transfection efficiency.

scholarly journals Non-Viral Delivery System and Targeted Bone Disease Therapy

2019 ◽  
Vol 20 (3) ◽  
pp. 565 ◽  
Author(s):  
Abdul Qadir ◽  
Yongguang Gao ◽  
Patil Suryaji ◽  
Ye Tian ◽  
Xiao Lin ◽  
...  
Keyword(s):  
Delivery System ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Calcium Phosphates ◽  
Delivery Systems ◽  
Cationic Lipids ◽  
Cationic Polymers ◽  
Bone Disorders ◽  
High Doses

Skeletal systems provide support, movement, and protection to the human body. It can be affected by several life suffering bone disorders such as osteoporosis, osteoarthritis, and bone cancers. It is not an easy job to treat bone disorders because of avascular cartilage regions. Treatment with non-specific drug delivery must utilize high doses of systemic administration, which may result in toxicities in non-skeletal tissues and low therapeutic efficacy. Therefore, in order to overcome such limitations, developments in targeted delivery systems are urgently needed. Although the idea of a general targeted delivery system using bone targeting moieties like bisphosphonates, tetracycline, and calcium phosphates emerged a few decades ago, identification of carrier systems like viral and non-viral vectors is a recent approach. Viral vectors have high transfection efficiency but are limited by inducing immunogenicity and oncogenicity. Although non-viral vectors possess low transfection efficiency they are comparatively safe. A number of non-viral vectors including cationic lipids, cationic polymers, and cationic peptides have been developed and used for targeted delivery of DNA, RNA, and drugs to bone tissues or cells with successful consequences. Here we mainly discuss such various non-viral delivery systems with respect to their mechanisms and applications in the specific targeting of bone tissues or cells. Moreover, we discuss possible therapeutic agents that can be delivered against various bone related disorders.

An Overview of Second Generation Nanoparticles− Nanostructure Lipid Carrier Drug Delivery System

2020 ◽  
Vol 13 (6) ◽  
pp. 5181-5189
Author(s):  
Prabhat Kumar Sahoo ◽  
Neha S.L ◽  
Arzoo Pannu
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Second Generation ◽  
Drug Loading ◽  
Scale Up ◽  
Delivery Systems ◽  
Route Of Administration ◽  
Random Structure ◽  
Stability Parameters

Lipids are used as vehicles for the preparation of various formulations prescribed for administrations, including emulsions, ointments, suspension, tablets, and suppositories. The first parental nano-emulsion was discovered from the 1950s when it was added to the intravenous administration of lipid and lipid-soluble substances. Lipid-based drug delivery systems are important nowadays. Solid nanoparticles (SLN) and Nanostructured lipid carriers (NLC) are very proficient due to the ease of production process, scale-up capability, bio-compatibility, the biodegradability of formulation components and other specific features of the proposed route. The administration or nature of the materials must be loaded into these delivery systems. The main objectives of this review are to discuss an overview of second-generation nanoparticles, their limitations, structures, and route of administration, with emphasis on the effectiveness of such formulations. NLC is the second generation of lipid nanoparticles having a structure like nanoemulsion. The first generation of nanoparticles was SLN. The difference between both of them is at its core. Both of them are a colloidal carrier in submicron size in the range of 40-1000 nm. NLC is the most promising novel drug delivery system over the SLN due to solving the problem of drug loading and drug crystallinity. Solid and liquid lipids combination in NLC formation, improve its quality as compare to SLN. NLC has three types of structures: random, amorphous, and multiple. The random structure containing solid-liquid lipids and consisting crystal and the liquid lipid irregular in shape; thereby enhance the ability of the lipid layer to pass through the membrane. The second is the amorphous structure. It is less crystalline in nature and can prevent the leakage of the loaded drug. The third type is multiple structures, which have higher liquid lipid concentrations than other types. The excipients used to form the NLC are bio-compatible, biodegradable and non-irritating, most of which can be detected using GRAS. NLC is a promising delivery system to deliver the drug through pulmonary, ocular, CNS, and oral route of administration. Various methods of preparation and composition of NLC influence its stability Parameters. In recent years at the educational level, the potential of NLC as a delivery mechanism targeting various organs has been investigated in detail.

scholarly journals Highly Osmotic Oxidized Sucrose-Crosslinked Polyethylenimine for Gene Delivery Systems

Pharmaceutics ◽  
2021 ◽  
Vol 13 (1) ◽  
pp. 87
Author(s):  
Jaehong Park ◽  
Kyusik Kim ◽  
Sohee Jeong ◽  
Migyeom Lee ◽  
Tae-il Kim
Keyword(s):  
Gene Delivery ◽  
Reductive Amination ◽  
Transfection Efficiency ◽  
Delivery Systems ◽  
Buffering Capacity ◽  
Serum Stability ◽  
High Osmolality ◽  
Cox 2 ◽  
Serum Free Conditions ◽  
Positively Charged

In this work, highly osmotic oxidized sucrose-crosslinked polyethylenimine (SP2K) polymers were developed for gene delivery systems, and the transfection mechanism is examined. First, periodate-oxidized sucrose and polyethylenimine 2K (PEI2K) were crosslinked with various feed ratios via reductive amination. The synthesis was confirmed by 1H NMR and FTIR. The synthesized SP2K polymers could form positively charged (~40 mV zeta-potential) and nano-sized (150–200 nm) spherical polyplexes with plasmid DNA (pDNA). They showed lower cytotoxicity than PEI25K but concentration-dependent cytotoxicity. Among them, SP2K7 and SP2K10 showed higher transfection efficiency than PEI25K in both serum and serum-free conditions, revealing the good serum stability. It was found that SP2K polymers possessed high osmolality and endosome buffering capacity. The transfection experiments with cellular uptake inhibitors suggest that the transfection of SP2K polymers would progress by multiple pathways, including caveolae-mediated endocytosis. It was also thought that caveolae-mediated endocytosis of SP2K polyplexes would be facilitated through cyclooxygenase-2 (COX-2) expression induced by high osmotic pressure of SP2K polymers. Confocal microscopy results also supported that SP2K polyplexes would be internalized into cells via multiple pathways and escape endosomes efficiently via high osmolality and endosome buffering capacity. These results demonstrate the potential of SP2K polymers for gene delivery systems.

scholarly journals What matters to patients? A mixed method study of the importance and consideration of oncology patient demands

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mathias WAELLI ◽  
Etienne Minvielle ◽  
Maria Ximena Acero ◽  
Khouloud Ba ◽  
Benoit Lalloué
Keyword(s):  
Cancer Patients ◽  
Mixed Method ◽  
New Technologies ◽  
Care Pathway ◽  
Scale Up ◽  
Healthcare Delivery ◽  
Delivery Systems ◽  
Breast Cancer Patients ◽  
Structured Interviews ◽  
Oncology Patient

Abstract Background A patient-centred approach is increasingly the mandate for healthcare delivery, especially with the growing emergence of chronic conditions. A relevant but often overlooked obstacle to delivering person-centred care is the identification and consideration of all demands based on individual experience, not only disease-based requirements. Mindful of this approach, there is a need to explore how patient demands are expressed and considered in healthcare delivery systems. This study aims to: (i) understand how different types of demands expressed by patients are taken into account in the current delivery systems operated by Health Care Organisations (HCOs); (ii) explore the often overlooked content of specific non-clinical demands (i.e. demands related to interactions between disease treatments and everyday life). Method We adopted a mixed method in two cancer centres, representing exemplary cases of organisational transformation: (i) circulation of a questionnaire to assess the importance that breast cancer patients attach to every clinical (C) and non-clinical (NC) demand identified in an exploratory inquiry, and the extent to which each demand has been taken into account based on individual experiences; (ii) a qualitative analysis based on semi-structured interviews exploring the content of specific NC demands. Results Further to the way in which the questionnaires were answered (573 answers/680 questionnaires printed) and the semi-structured interviews (36) with cancer patients, results show that NC demands are deemed by patients to be almost as important as C demands (C = 6.53/7 VS. NC = 6.13), but are perceived to be considered to a lesser extent in terms of pathway management (NC = 4.02 VS C = 5.65), with a significant variation depending on the type of non-clinical demands expressed. Five types of NC demands can be identified: demands relating to daily life, alternative medicine, structure of the treatment pathway, administrative and logistic assistance and demands relating to new technologies. Conclusions This study shows that HCOs should be able to consider non-clinical demands in addition to those referring to clinical needs. These demands require revision of the healthcare professionals’ mandate and transition from a supply-orientated system towards a demand-driven approach throughout the care pathway. Other sectors have developed hospitality management, mass customisation and personalisation to scale up approaches that could serve as inspiring examples.

scholarly journals Сationic liposomes as delivery systems for nucleic acids

2020 ◽  
Vol 15 (1) ◽  
pp. 7-27
Author(s):  
A. A. Mikheev ◽  
E. V. Shmendel ◽  
E. S. Zhestovskaya ◽  
G. V. Nazarov ◽  
M. A. Maslov
Keyword(s):  
Gene Therapy ◽  
Nucleic Acids ◽  
Serum Proteins ◽  
Transfection Efficiency ◽  
Biological Fluids ◽  
Genetic Material ◽  
Cationic Liposomes ◽  
Delivery Systems ◽  
Cationic Lipids

Objectives. Gene therapy is based on the introduction of genetic material into cells, tissues, or organs for the treatment of hereditary or acquired diseases. A key factor in the success of gene therapy is the development of delivery systems that can efficiently transfer genetic material to the place of their therapeutic action without causing any associated side effects. Over the past 10 years, significant effort has been directed toward creating more efficient and biocompatible vectors capable of transferring nucleic acids (NAs) into cells without inducing an immune response. Cationic liposomes are among the most versatile tools for delivering NAs into cells; however, the use of liposomes for gene therapy is limited by their low specificity. This is due to the presence of various biological barriers to the complex of liposomes with NA, including instability in biological fluids, interaction with serum proteins, plasma and nuclear membranes, and endosomal degradation. This review summarizes the results of research in recent years on the development of cationic liposomes that are effective in vitro and in vivo. Particular attention is paid to the individual structural elements of cationic liposomes that determine the transfection efficiency and cytotoxicity. The purpose of this review was to provide a theoretical justification of the most promising choice of cationic liposomes for the delivery of NAs into eukaryotic cells and study the effect of the composition of cationic lipids (CLs) on the transfection efficiency in vitro.Results. As a result of the analysis of the related literature, it can be argued that one of the most promising delivery systems of NAs is CL based on cholesterol and spermine with the addition of a helper lipid DOPE. In addition, it was found that varying the composition of cationic liposomes, the ratio of CL to NA, or the size and zeta potential of liposomes has a significant effect on the transfection efficiency.Conclusions. Further studies in this direction should include optimization of the conditions for obtaining cationic liposomes, taking into account the physicochemical properties and established laws. It is necessary to identify mechanisms that increase the efficiency of NA delivery in vitro by searching for optimal structures of cationic liposomes, determining the ratio of lipoplex components, and studying the delivery efficiency and properties of multicomponent liposomes.

scholarly journals Biodegradable Gene Carriers Containing Rigid Aromatic Linkage with Enhanced DNA Binding and Cell Uptake

Polymers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 1080 ◽  
Author(s):  
Ju-Hui Zhang ◽  
Hui-Zhen Yang ◽  
Ji Zhang ◽  
Yan-Hong Liu ◽  
Xi He ◽  
...  
Keyword(s):  
Dna Binding ◽  
Laser Scanning ◽  
Transfection Efficiency ◽  
Laser Scanning Microscopy ◽  
Cell Uptake ◽  
Confocal Laser ◽  
Viral Gene ◽  
Cationic Polymers ◽  
Aromatic Rings ◽  
Gene Carriers

The linking and modification of low molecular weight cationic polymers (oligomers) has become an attracted strategy to construct non-viral gene carriers with good transfection efficiency and much reduced cytotoxicity. In this study, PEI 600 Da was linked by biodegradable bridges containing rigid aromatic rings. The introduction of aromatic rings enhanced the DNA-binding ability of the target polymers and also improved the stability of the formed polymer/DNA complexes. The biodegradable property and resulted DNA release were verified by enzyme stimulated gel electrophoresis experiment. These materials have lower molecular weights compared to PEI 25 kDa, but exhibited higher transfection efficiency, especially in the presence of serum. Flow cytometry and confocal laser scanning microscopy results indicate that the polymers with aromatic rings could induce higher cellular uptake. This strategy for the construction of non-viral gene vectors may be applied as an efficient and promising method for gene delivery.

Poly(β-amino ester)-based gene delivery systems: From discovery to therapeutic applications

2019 ◽  
Vol 310 ◽  
pp. 155-187 ◽  
Author(s):  
Rosemeyre A. Cordeiro ◽  
Arménio Serra ◽  
Jorge F.J. Coelho ◽  
Henrique Faneca
Keyword(s):  
Gene Delivery ◽  
Delivery Systems ◽  
Amino Ester ◽  
Therapeutic Applications

NON-CONDENSING POLYMERIC GENE DELIVERY SYSTEMS: PRINCIPLES AND APPLICATIONS

Nano LIFE ◽  
2010 ◽  
Vol 01 (03n04) ◽  
pp. 219-237 ◽  
Author(s):  
SHARDOOL JAIN ◽  
HUSAIN ATTARWALA ◽  
MANSOOR AMIJI
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Viral Vectors ◽  
Transfection Efficiency ◽  
Contemporary Literature ◽  
Delivery Systems ◽  
Expression Of Genes ◽  
Cytoplasmic Dna ◽  
Polymeric Delivery ◽  
Systemic Gene Delivery

Gene therapy holds tremendous promise in prevention and treatment of diseases as the approach is based on regulating the expression of genes that are responsible for pathological conditions. The biggest bottleneck for gene delivery has been the development of safe and efficacious delivery systems. Although non-viral vectors are considered as much safer options than their viral counterparts, they suffer from low transfection efficiency. In this review, we highlight the role of non-condensing polymeric delivery systems for oral and systemic gene delivery. Using evidence from contemporary literature, non-condensing polymeric microparticle and nanoparticle systems afford physical encapsulation of the nucleic acid construct and can be engineered for targeted delivery to tissues and cells. Additionally, these systems have shown less toxicity and afford sustained cytoplasmic DNA delivery for efficient nuclear uptake and transfection for both DNA vaccines and therapeutic genes.

A dendritic catiomer with an MOF motif for the construction of safe and efficient gene delivery systems

2017 ◽  
Vol 5 (42) ◽  
pp. 8322-8329 ◽  
Author(s):  
Shuqi Dong ◽  
Qixian Chen ◽  
Wei Li ◽  
Zhu Jiang ◽  
Jianbiao Ma ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Gold Standard ◽  
Transfection Efficiency ◽  
A549 Cells ◽  
Delivery Systems ◽  
The Core ◽  
Efficient Gene

The dendritic catiomer using biocompatible Zr-MOFs as the core exhibited a markedly higher transfection efficiency and lower cytotoxicity than the commercial gold standard branched PEI25k in A549 cells.

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