scholarly journals Albumin coated liposomes: a novel platform for macrophage specific drug delivery

2011 ◽  
Vol 1 (1) ◽  
pp. 2 ◽  
Author(s):  
Clément Vuarchey ◽  
Sushil Kumar ◽  
Reto Schwendener
Keyword(s):  
Drug Delivery ◽  
Drug Carrier ◽  
Cell Types ◽  
Specific Drug ◽  
Splenic Macrophages ◽  
Peg Liposomes ◽  
Short Time ◽  
Liposome Surface

Here we report a new and efficient approach of macrophage specific drug delivery by coating liposomes with albumin. Activated albumin was reacted with liposomes containing polyethylene glycol (PEG) as hydrophilic spacers to create a flexible layer of covalently bound albumin molecules on the liposome surface. Albumin coated liposomes were taken up faster and more efficiently than uncoated liposomes by murine macrophages. Liposome uptake was significantly higher in macropha - ges as compared to other cell types tested (endothelial cells, fibroblasts, tumor cells), suggesting specificity for macrophages. In vivo, splenic macrophages phagocytosed BSA coated liposomes (BSA-L) at faster rates compared to conventional liposomes (L) and PEG liposomes (PEG-L). To prove the effectiveness of this new macrophage specific drug carrier, the bisphosphonates clodronate and zoledronate were encapsulated in BSA-L and compared with conventional liposomes. <em>In vitro</em>, treatment of macrophages with clodronate or zoledronate in BSA-L led to cytotoxic activity within a very short time and to up to 50-fold reduced IC50 concentrations. <em>In vivo</em>, clodronate encapsulated in BSA-L depleted splenic macrophages at a 5-fold lower concentration as conventional clodronate-liposomes. Our results highlight the pharmaceutical benefits of albumin-coated liposomes for macrophage specific drug delivery.

In vitro and in vivo evaluation of an oral system for time and/or site-specific drug delivery

2001 ◽  
Vol 73 (1) ◽  
pp. 103-110 ◽  
Author(s):  
M.E Sangalli ◽  
A Maroni ◽  
L Zema ◽  
C Busetti ◽  
F Giordano ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Specific Drug ◽  
In Vivo Evaluation ◽  
Site Specific

scholarly journals Efficient Development of Platform Cell Lines Using CRISPR-Cas9 and Transcriptomics Analysis

2020 ◽  
Author(s):  
Andrew Tae-Jun Kwon ◽  
Kohta Mohri ◽  
Satoshi Takizawa ◽  
Takahiro Arakawa ◽  
Maiko Takahashi ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Target Genes ◽  
Cell Types ◽  
Target Antigen ◽  
Drug Conjugates ◽  
Targeted Mutation ◽  
Additional Cell ◽  
Delivery Platform

AbstractAntibody-drug conjugates offers many advantages as a drug delivery platform that allows for highly specific targeting of cell types and genes. Ideally, testing the efficacy of these systems requires two cell types to be different only in the gene targeted by the drug, with the rest of the cellular machinery unchanged, in order to minimize other potential differences from obscuring the effects of the drug. In this study, we created multiple variants of U87MG cells with targeted mutation in the TP53 gene using the CRISPR-Cas9 system, and determined that their major transcriptional differences stem from the loss of p53 function. Using the transcriptome data, we predicted which mutant clones would have less divergent phenotypes from the wild type and thereby serve as the best candidates to be used as drug delivery testing platforms. Further in vitro and in vivo assays of cell morphology, proliferation rate and target antigen-mediated uptake supported our predictions. Based on the combined analysis results, we successfully selected the best qualifying mutant clone. This study serves as proof-of-principle of the approach and paves the way for extending to additional cell types and target genes.

Stimuli-responsive Polymeric nanosystems for therapeutic applications

2021 ◽  
Vol 27 ◽  
Author(s):  
Mayank Handa ◽  
Ajit Singh ◽  
S.J.S. Flora ◽  
Rahul Shukla
Keyword(s):  
Drug Delivery ◽  
Metallic Nanoparticles ◽  
Drug Delivery Systems ◽  
Polymeric Nanoparticles ◽  
Drug Loading ◽  
Delivery Systems ◽  
Specific Drug ◽  
Stimuli Responsive

Background: Recent past decades have reported emerging of polymeric nanoparticles as a promising technique for controlled and targeted drug delivery. As nanocarriers, they have high drug loading and delivery to the specific site or targeted cells with an advantage of no drug leakage within en route and unloading of a drug in a sustained fashion at the site. These stimuli-responsive systems are functionalized in dendrimers, metallic nanoparticles, polymeric nanoparticles, liposomal nanoparticles, quantum dots. Purpose of Review: The authors reviewed the potential of smart stimuli-responsive carriers for therapeutic application and their behavior in external or internal stimuli like pH, temperature, redox, light, and magnet. These stimuli-responsive drug delivery systems behave differently in In vitro and In vivo drug release patterns. Stimuli-responsive nanosystems include both hydrophilic and hydrophobic systems. This review highlights the recent development of the physical properties and their application in specific drug delivery. Conclusion: The stimuli (smart, intelligent, programmed) drug delivery systems provide site-specific drug delivery with potential therapy for cancer, neurodegenerative, lifestyle disorders. As development and innovation, the stimuli-responsive based nanocarriers are moving at a fast pace and huge demand for biocompatible and biodegradable responsive polymers for effective and safe delivery.

PLA/PLGA nanoparticles for delivery of drugs across the blood-brain barrier

2013 ◽  
Vol 2 (3) ◽  
pp. 241-257 ◽  
Author(s):  
Jingyan Li ◽  
Cristina Sabliov
Keyword(s):  
Drug Delivery ◽  
Blood Brain Barrier ◽  
Polymeric Nanoparticles ◽  
Drug Carrier ◽  
Plga Nanoparticles ◽  
Brain Barrier ◽  
Poly Lactic Acid ◽  
Blood Brain

AbstractThe blood-brain barrier (BBB), which protects the central nervous system (CNS) from unnecessary substances, is a challenging obstacle in the treatment of CNS disease. Many therapeutic agents such as hydrophilic and macromolecular drugs cannot overcome the BBB. One promising solution is the employment of polymeric nanoparticles (NPs) such as poly (lactic-co-glycolic acid) (PLGA) NPs as drug carrier. Over the past few years, significant breakthroughs have been made in developing suitable PLGA and poly (lactic acid) (PLA) NPs for drug delivery across the BBB. Recent advances on PLGA/PLA NPs enhanced neural delivery of drugs are reviewed in this paper. Both in vitro and in vivo studies are included. In these papers, enhanced cellular uptake and therapeutic efficacy of drugs delivered with modified PLGA/PLA NPs compared with free drugs or drugs delivered by unmodified PLGA/PLA NPs were shown; no significant in vitro cytotoxicity was observed for PLGA/PLA NPs. Surface modification of PLGA/PLA NPs by coating with surfactants/polymers or covalently conjugating the NPs with targeting ligands has been confirmed to enhance drug delivery across the BBB. Most unmodified PLGA NPs showed low brain uptake (<1%), which indirectly confirms the safety of PLGA/PLA NPs used for other purposes than treating CNS diseases.

Adsorption of Alendronate onto Biomimetic Apatite Nanocrystals to Develop Drug Carrier Coating for Bone Implants

2012 ◽  
Vol 529-530 ◽  
pp. 475-479 ◽  
Author(s):  
Ruggero Bosco ◽  
Michele Iafisco ◽  
Jeroen van den Beucken ◽  
Sander C.G. Leeuwenburgh ◽  
John A. Jansen
Keyword(s):  
Drug Delivery ◽  
Surface Engineering ◽  
Drug Carrier ◽  
Local Treatment ◽  
Titanium Implants ◽  
Bone Implants ◽  
Bone Implant ◽  
Biomimetic Apatite

The possibility to develop a bone implant with bioactive aspects and in situ drug-delivery properties, in order to provide local treatment in vivo, is a big challenge. Where conventional surface modifications for bone implants focused on the deposition of ceramic (mostly calcium phosphate, CaP) coatings, current surface engineering approaches attempt to incorporate active features to render bone implant surfaces capable to direct biological performance. Biomimetic apatite nanocrystals (nAp) represent, among the CaPs, an elective material for bone applications and their surface functionalization with drugs allows them to act as a drug-delivery vehicle. Since load-bearing bone implants are increasingly used in patients with compromised health conditions, surface engineering is important to warrant the performance of these implants under such conditions. In view of this, bisphosphonates (BPs) represent a treatment modality for a variety of disorders of bone metabolism associated to bone loss, including Paget's bone disease, osteoporosis, fibrous dysplasia and bone metastases. In this work, we have synthesized and characterized bioinspired nAp and evaluated their functionalization with alendronate. In vitro tests will be used to evaluate the efficacy of the functionalized compound to impede the formation of osteoclasts and to show that alendronate-functionalized nAp can significantly reduce osteoclasteogenesis. Finally, alendronate-functionalized nAp (FnAp) has been deposited on titanium implants via the electrospray deposition technique in order to develop inorganic-organic coatings for bone implants with improved functionality.

scholarly journals Steroid Eluting Esophageal-Targeted Drug Delivery Devices for Treatment of Eosinophilic Esophagitis

Polymers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 557
Author(s):  
Alka Prasher ◽  
Roopali Shrivastava ◽  
Denali Dahl ◽  
Preetika Sharma-Huynh ◽  
Panita Maturavongsadit ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Drug Release ◽  
Porcine Model ◽  
Pharmacokinetic Studies ◽  
Specific Drug ◽  
In Vitro Drug Release ◽  
Release Studies ◽  
3D Printed

Eosinophilic esophagitis (EoE) is a chronic atopic disease that has become increasingly prevalent over the past 20 years. A first-line pharmacologic option is topical/swallowed corticosteroids, but these are adapted from asthma preparations such as fluticasone from an inhaler and yield suboptimal response rates. There are no FDA-approved medications for the treatment of EoE, and esophageal-specific drug formulations are lacking. We report the development of two novel esophageal-specific drug delivery platforms. The first is a fluticasone-eluting string that could be swallowed similar to the string test “entero-test” and used for overnight treatment, allowing for a rapid release along the entire length of esophagus. In vitro drug release studies showed a target release of 1 mg/day of fluticasone. In vivo pharmacokinetic studies were carried out after deploying the string in a porcine model, and our results showed a high local level of fluticasone in esophageal tissue persisting over 1 and 3 days, and a minimal systemic absorption in plasma. The second device is a fluticasone-eluting 3D printed ring for local and sustained release of fluticasone in the esophagus. We designed and fabricated biocompatible fluticasone-loaded rings using a top-down, Digital Light Processing (DLP) Gizmo 3D printer. We explored various strategies of drug loading into 3D printed rings, involving incorporation of drug during the print process (pre-loading) or after printing (post-loading). In vitro drug release studies of fluticasone-loaded rings (pre and post-loaded) showed that fluticasone elutes at a constant rate over a period of one month. Ex vivo pharmacokinetic studies in the porcine model also showed high tissue levels of fluticasone and both rings and strings were successfully deployed into the porcine esophagus in vivo. Given these preliminary proof-of-concept data, these devices now merit study in animal models of disease and ultimately subsequent translation to testing in humans.

Colonic Bacterial Enzymes

2018 ◽  
pp. 71-99 ◽  
Author(s):  
Srushti M. Tambe ◽  
Namita D. Desai
Keyword(s):  
Drug Delivery ◽  
Drug Delivery Systems ◽  
Dosage Forms ◽  
Specific Drug ◽  
Bacterial Enzymes ◽  
In Vitro Drug Release ◽  
Pharmaceutical Dosage Forms ◽  
Colon Specific Drug Delivery

This chapter reviews various enzymes produced by the colonic microflora and their utilization in the development of pharmaceutical dosage forms to achieve colon-specific drug delivery. This chapter discusses the applications of colonic bacterial enzymes in order to surrogate colonic conditions in vivo so as to evaluate in vitro drug release from microbially triggered/enzymatically triggered colon-specific drug delivery systems. This chapter also discusses different methods to produce colonic bacterial enzymes as well as use of probiotics as a source to produce colonic bacterial enzymes.

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