scholarly journals Lipid Nanoparticles for Organ-Specific mRNA Therapeutic Delivery

Pharmaceutics ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 1675
Author(s):  
Magdalena M. Żak ◽  
Lior Zangi
Keyword(s):  
Lipid Nanoparticles ◽  
Target Cells ◽  
Therapeutic Delivery ◽  
The Past ◽  
Recent Success ◽  
Organ Specific ◽  
Mrna Therapeutics ◽  
Mrna Technology ◽  
Specific Mrna

Advances in the using in vitro transcribed (IVT) modRNA in the past two decades, especially the tremendous recent success of mRNA vaccines against SARS-CoV-2, have brought increased attention to IVT mRNA technology. Despite its well-known use in infectious disease vaccines, IVT modRNA technology is being investigated mainly in cancer immunotherapy and protein replacement therapy, with ongoing clinical trials in both areas. One of the main barriers to progressing mRNA therapeutics to the clinic is determining how to deliver mRNA to target cells and protect it from degradation. Over the years, many different vehicles have been developed to tackle this issue. Desirable vehicles must be safe, stable and preferably organ specific for successful mRNA delivery to clinically relevant cells and tissues. In this review we discuss various mRNA delivery platforms, with particular focus on attempts to create organ-specific vehicles for therapeutic mRNA delivery.

In situ activation of mouse alveolar macrophages by aerosolized liposomal IFN-gamma and muramyl tripeptide

1996 ◽  
Vol 270 (3) ◽  
pp. L429-L434 ◽  
Author(s):  
P. Goldbach ◽  
S. Dumont ◽  
R. Kessler ◽  
P. Poindron ◽  
A. Stamm
Keyword(s):  
Alveolar Macrophages ◽  
Peritoneal Macrophages ◽  
Target Cells ◽  
Tumoricidal Activity ◽  
Ifn Gamma ◽  
In Situ Activation ◽  
Organ Specific ◽  
Thawing Procedure

Interferon-gamma (IFN-gamma) was entrapped with an efficiency of 30-40% in muramyl tripeptide-containing liposomes by a freeze-thawing procedure. A microcytotoxicity assay was developed to measure the tumoricidal activity of mouse alveolar macrophages (AM) against tumoral target cells with a colorimetric viability test. Free IFN-gamma and liposomal muramyl tripeptide phosphatidylethanolamine (MTP-PE) were found to be only slightly effective to activate in vitro AM, whereas encapsulation of both INF-gamma and MTP-PE within the same liposomes produced higher activation of AM. Aerosolized IFN-gamma and liposomal immunomodulators enhanced antitumor properties of AM recovered in mice 24 h postinhalation. Whereas free IFN-gamma also induced a substantial activation of peritoneal macrophages, liposomal encapsulation significantly reduced the systemic activity of inhaled immunomodulators. This approach provides a useful model for the compartmentalized organ-specific activation of AM in mice.

Ultrastructural Changes in Tumor Cells During Human Peripheral Blood Monocyte-Mediated Cytotoxicity

1981 ◽  
Vol 39 ◽  
pp. 452-453
Author(s):  
K. E. Muse ◽  
D. G. Fischer ◽  
H. S. Koren
Keyword(s):  
Target Cell ◽  
Human Peripheral Blood ◽  
Mononuclear Phagocytes ◽  
Ultrastructural Changes ◽  
Target Cells ◽  
Limited Information ◽  
Blood Monocytes ◽  
Tumoricidal Activity ◽  
Activated State

Mononuclear phagocytes, a pluripotential cell line, manifest an array of basic extracellular functions. Among these physiological regulatory functions is the expression of spontaneous cytolytic potential against tumor cell targets.The limited observations on human cells, almost exclusively blood monocytes, initially reported limited or a lack of tumoricidal activity in the absence of antibody. More recently, freshly obtained monocytes have been reported to spontaneously impair the biability of tumor target cells in vitro (Harowitz et al., 1979; Montavani et al., 1979; Hammerstrom, 1979). Although the mechanism by which effector cells express cytotoxicity is poorly understood, discrete steps can be distinguished in the process of cell mediated cytotoxicity: recognition and binding of effector to target cells,a lethal-hit stage, and subsequent lysis of the target cell. Other important parameters in monocyte-mediated cytotoxicity include, activated state of the monocyte, effector cell concentrations, and target cell suseptibility. However, limited information is available with regard to the ultrastructural changes accompanying monocyte-mediated cytotoxicity.

STEROID HORMONE METABOLISM IN RESPONSIVE TISSUES IN VITRO

1971 ◽  
Vol 68 (1_Suppl) ◽  
pp. S279-S294 ◽  
Author(s):  
Paul Robel
Keyword(s):  
Steroid Hormone ◽  
Physiological Activity ◽  
Physiological State ◽  
Target Cells ◽  
Target Tissue ◽  
Hormone Metabolism ◽  
Metabolizing Enzymes ◽  
Relationship Of

ABSTRACT Of the information available on steroid hormone metabolism in responsive tissues, only that relating hormone metabolism to physiological activity is reviewed, i. e. metabolite activity in isolated in vitro systems, binding of metabolites to target tissue receptors, specific steroid hormone metabolizing enzymes and relationship of hormone metabolism to target organ physiological state. Further, evidence is presented in the androgen field, demonstrating 5α-reduced metabolites, formed inside the target cells, as active compounds. This has led to a consideration of testosterone as a »prehormone«. The possibility that similar events take place in tissues responding to progesterone is discussed. Finally, the role of hormone metabolism in the regulation of hormone availability and/or renewal in target cells is discussed. In this context, reference is made to the potential role of plasma binding proteins and cytosol receptors.

Development of Solid Lipid Nanoparticles of Lamivudine for Brain Targeting

2009 ◽  
Vol 1 (1) ◽  
Author(s):  
Pravin Patil ◽  
Anil Sharma ◽  
Subhash Dadarwal ◽  
Vijay Sharma
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Solid Lipid Nanoparticles ◽  
Rotation Speed ◽  
Lipid Nanoparticles ◽  
Brain Targeting ◽  
Brain Penetration ◽  
Solid Lipid ◽  
Diffusion Technique

The objective of present investigation was to enhance brain penetration of Lamivudine, one of the most widely used drugs for the treatment of AIDS. This was achieved through incorporating the drug into solid lipid nanoparticles (SLN) prepared by using emulsion solvent diffusion technique. The formulations were characterized for surface morphology, size and size distribution, percent drug entrapment and drug release. The optimum rotation speed, resulting into better drug entrapment and percent yield, was in the range of 1000-1250 r/min. In vitro cumulative % drug release from optimized SLN formulation was found 40-50 % in PBS (pH-7.4) and SGF (pH-1.2) respectively for 10 h. After 24 h more than 65 % of the drug was released from all formulations in both mediums meeting the requirement for drug delivery for prolong period of time.

Preparation, Characterization and In-vitro release of Piroxicam-loaded Solid Lipid Nanoparticles

2010 ◽  
Vol 3 (3) ◽  
pp. 1136-1146
Author(s):  
V K Verma ◽  
Ram A
Keyword(s):  
Electron Microscopy ◽  
Particle Size ◽  
Solid Lipid Nanoparticles ◽  
In Vitro Release ◽  
Entrapment Efficiency ◽  
Lipid Nanoparticles ◽  
Diffusion Method ◽  
Solid Lipid ◽  
Vitro Release

 Solid lipid nanoparticles (SLNs) of piroxicam where produced by solvent emulsification diffusion method in a solvent saturated system. The SLNs where composed of tripamitin lipid, polyvinyl alcohol (PVAL) stabilizer, and solvent ethyl acetate. All the formulation were subjected to particle size analysis, zeta potential, drug entrapment efficiency, percent drug loading determination and in-vitro release studies. The SLNs formed were nano-size range with maximum entrapment efficiency. Formulation with 435nm in particle size and 85% drug entrapment was subjected to scanning electron microscopy (SEM) and transmission electron microscopy (TEM) for surface morphology, differential scanning calorimetry (DSC) for thermal analysis and short term stability studies. SEM and TEM confirm that the SLNs are nanometric size and circular in shape. The drug release behavior from SLNs suspension exhibited biphasic pattern with an initial burst and prolong release over 24 h. 

Solid Lipid Nanoparticles for Topical Delivery of Acitretin for the Treatment of Psoriasis by Design of Experiment

2020 ◽  
Vol 12 (2) ◽  
pp. 4474-4491
Author(s):  
Rajkumar Aland ◽  
Ganesan M ◽  
P. Rajeswara Rao ◽  
Bhikshapathi D. V. R. N.
Keyword(s):  
Particle Size ◽  
Drug Release ◽  
Solid Lipid Nanoparticles ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Lipid Nanoparticles ◽  
Tem Analysis ◽  
In Vitro Drug Release ◽  
Solid Lipid

The main objective for this investigation is to develop and optimize the solid lipid nanoparticles formulation of acitretin for the effective drug delivery. Acitretin loaded SLNs were prepared by hot homogenization followed by the ultrasonication using Taguchi’s orthogonal array with eight parameters that could affect the particle size and entrapment efficiency. Based on the results from the analyses of the responses obtained from Taguchi design, three different independent variables including surfactant concentration (%), lipid to drug ratio (w/w) and sonication time (s) were selected for further investigation using central composite design. The  lipid Dynasan-116, surfactant poloxomer-188 and co surfactant egg lecithin resulted in better percent drug loading and evaluated for particle size, zeta potential, drug entrapment efficiency, in vitro drug release and stability. All parameters were found to be in an acceptable range. TEM analysis has demonstrated the presence of individual nanoparticles in spherical shape and the results were compatible with particle size measurements.  In vitro drug release of optimized SLN formulation (F2) was found to be 95.63 ± 1.52%, whereas pure drug release was 30.12 after 60 min and the major mechanism of drug release follows first order kinetics release data for optimized formulation (F2) with non-Fickian (anomalous) with a strong correlation coefficient (R2 = 0.94572) of Korsemeyer-Peppas model. The total drug content of acitretin gel formulation was found to 99.86 ± 0.012% and the diameter of gel formulation was 6.9 ± 0.021 cm and that of marketed gel was found to be 5.7 ± 0.06 cm, indicating better spreadability of SLN based gel formulation. The viscosity of gel formulation at 5 rpm was found to be 6.1 x 103 ± 0.4 x 103 cp. The release rate (flux) of acitretin across the membrane and excised skin differs significantly, which indicates about the barrier properties of skin. The flux value for SLN based gel formulation (182.754 ± 3.126 μg cm−2 h−1) was found to be higher than that for marketed gel (122.345 ± 4.786 μg cm−2 h−1). The higher flux and Kp values of SLN based gel suggest that it might be able to enter the skin easily as compared with marketed gel with an advantage of low interfacial tension of the emulsifier film that ensures an excellent contact to the skin. This topically oriented SLN based gel formulation could be useful in providing site-specific dermal treatment of psoriasis

Bioengineered in vitro Vascular Models for Applications in Interventional Radiology

2019 ◽  
Vol 24 (45) ◽  
pp. 5367-5374 ◽  
Author(s):  
Xiaoyun Li ◽  
Seyed M. Moosavi-Basri ◽  
Rahul Sheth ◽  
Xiaoying Wang ◽  
Yu S. Zhang
Keyword(s):  
Interventional Radiology ◽  
Animal Models ◽  
Blood Vessels ◽  
In Vitro Models ◽  
The Past ◽  
Endovascular Interventions ◽  
Conventional Animal ◽  
Vascular Structures

The role of endovascular interventions has progressed rapidly over the past several decades. While animal models have long-served as the mainstay for the advancement of this field, the use of in vitro models has become increasingly widely adopted with recent advances in engineering technologies. Here, we review the strategies, mainly including bioprinting and microfabrication, which allow for fabrication of biomimetic vascular models that will potentially serve to supplement the conventional animal models for convenient investigations of endovascular interventions. Besides normal blood vessels, those in diseased states, such as thrombosis, may also be modeled by integrating cues that simulate the microenvironment of vascular disorders. These novel engineering strategies for the development of biomimetic in vitro vascular structures will possibly enable unconventional means of studying complex endovascular intervention problems that are otherwise hard to address using existing models.

Solid Lipid Nanoparticles (SLNs) Gels for Topical Delivery of Aceclofenac in vitro and in vivo Evaluation

2013 ◽  
Vol 10 (6) ◽  
pp. 656-666 ◽  
Author(s):  
Sandipan Dasgupta ◽  
Surajit Ghosh ◽  
Subhabrata Ray ◽  
Bhaskar Mazumder
Keyword(s):  
Solid Lipid Nanoparticles ◽  
Topical Delivery ◽  
Lipid Nanoparticles ◽  
In Vivo Evaluation ◽  
Solid Lipid

Novel Findings of Anti-cancer Property of Propofol

2018 ◽  
Vol 18 (2) ◽  
pp. 156-165 ◽  
Author(s):  
Jiaqiang Wang ◽  
Chien-shan Cheng ◽  
Yan Lu ◽  
Xiaowei Ding ◽  
Minmin Zhu ◽  
...  
Keyword(s):  
General Anesthesia ◽  
Cancer Progression ◽  
Molecular Mechanisms ◽  
Intravenous Anesthetic ◽  
The Past ◽  
Anti Cancer ◽  
Underlying Mechanisms ◽  
Recent Attention

Background: Propofol, a widely used intravenous anesthetic agent, is traditionally applied for sedation and general anesthesia. Explanation: Recent attention has been drawn to explore the effect and mechanisms of propofol against cancer progression in vitro and in vivo. Specifically, the proliferation-inhibiting and apoptosis-inducing properties of propofol in cancer have been studied. However, the underlying mechanisms remain unclear. Conclusion: This review focused on the findings within the past ten years and aimed to provide a general overview of propofol's malignance-modulating properties and the potential molecular mechanisms.

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