Opportunities and Challenges in Targeted Carrier-Based Intracellular Drug Delivery: Increased Efficacy and Reduced Toxicity

2019 ◽  
pp. 403-431
Author(s):  
Sagar Dhoble ◽  
Shrikant Dhage ◽  
Sreeranjini Pulakkat ◽  
Vandana B. Patravale
Keyword(s):  
Drug Delivery ◽  
Intracellular Drug Delivery ◽  
Reduced Toxicity

Doxorubicin Loaded Nanoparticle Consisting of Chitosan and Mannose Modified Graphene Oxide for Intracellular Drug Delivery and Anti-tumor Activity

2020 ◽  
Vol 13 (5) ◽  
pp. 5155-5164
Author(s):  
Meena K. S. ◽  
Sonia K ◽  
Alamelu Bai S
Keyword(s):  
Drug Delivery ◽  
Graphene Oxide ◽  
Drug Delivery System ◽  
Delivery System ◽  
In Vitro Release ◽  
Cancer Drug ◽  
Hemolysis Assay ◽  
Functionalized Graphene Oxide ◽  
Intracellular Drug Delivery ◽  
Modified Graphene Oxide

In order to develop the efficiency and the specificity of anticancer drug delivery, we have designed an innovative nanocarrier. The nanocarrier system comprises of a multifunctional graphene oxide nanoparticle-based drug delivery system (GO-CS-M-DOX) as a novel platform for intracellular drug delivery of doxorubicin (DOX). Firstly, graphene oxide (GO) was synthesized by hummer’s method whose surface was functionalized by chitosan (CS) in order to obtain a more precise drug delivery, the system was then decorated with mannose (M). Further conjugation of an anti-cancer drug doxorubicin to the nanocarrier system resulted in GO-CS-M-DOX drug delivery system. The resultant conjugate was characterized for its physio-chemical properties and its biocompatibility was evaluated via hemolysis assay. The drug entrapment efficiency is as high as 90% and in vitro release studies of DOX under pH 5.3 is significantly higher than that under pH 7.4. The anticancer activity of the synthesized drug delivery system was studied by 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay against MCF-7 cell line. These results stated that the pH dependent multifunctional doxorubicin- chitosan functionalized graphene oxide based nanocarrier system, could lead to a promising and potential platform for intracellular delivery and cytotoxicity activity for variety of anticancer drugs.   

scholarly journals Single Domain Antibodies as Carriers for Intracellular Drug Delivery: A Proof of Principle Study

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 927
Author(s):  
Sebas D. Pronk ◽  
Erik Schooten ◽  
Jurgen Heinen ◽  
Esra Helfrich ◽  
Sabrina Oliveira ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Single Domain ◽  
Drug Conjugates ◽  
Intracellular Drug Delivery ◽  
Internalization Rate ◽  
Single Domain Antibodies ◽  
Different Characteristics

Antibody-drug conjugates (ADCs) are currently used for the targeted delivery of drugs to diseased cells, but intracellular drug delivery and therefore efficacy may be suboptimal because of the large size, slow internalization and ineffective intracellular trafficking of the antibody. Using a phage display method selecting internalizing phages only, we developed internalizing single domain antibodies (sdAbs) with high binding affinity to rat PDGFRβ, a receptor involved in different types of diseases. We demonstrate that these constructs have different characteristics with respect to internalization rates but all traffic to lysosomes. To compare their efficacy in targeted drug delivery, we conjugated the sdAbs to a cytotoxic drug. The conjugates showed improved cytotoxicity correlating to their internalization speed. The efficacy of the conjugates was inhibited in the presence of vacuolin-1, an inhibitor of lysosomal maturation, suggesting lysosomal trafficking is needed for efficient drug release. In conclusion, sdAb constructs with different internalization rates can be designed against the same target, and sdAbs with a high internalization rate induce more cell killing than sdAbs with a lower internalization rate in vitro. Even though the overall efficacy should also be tested in vivo, sdAbs are particularly interesting formats to be explored to obtain different internalization rates.

pH-Responsive Poly(styrene-alt-maleic anhydride) Alkylamide Copolymers for Intracellular Drug Delivery

2006 ◽  
Vol 7 (8) ◽  
pp. 2407-2414 ◽  
Author(s):  
Scott M. Henry ◽  
Mohamed E. H. El-Sayed ◽  
Christopher M. Pirie ◽  
Allan S. Hoffman ◽  
Patrick S. Stayton
Keyword(s):  
Drug Delivery ◽  
Maleic Anhydride ◽  
Ph Responsive ◽  
Intracellular Drug Delivery

pH-sensitive polyion complex micelles for tunable intracellular drug delivery

2015 ◽  
Vol 213 ◽  
pp. e55
Author(s):  
Jinjin Chen ◽  
Ying Zhang ◽  
Jianxun Ding ◽  
Chunsheng Xiao ◽  
Xiuli Zhuang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Ph Sensitive ◽  
Polyion Complex ◽  
Polyion Complex Micelles ◽  
Intracellular Drug Delivery ◽  
Complex Micelles

Pillar[5]arene based supramolecular prodrug micelles with pH induced aggregate behavior for intracellular drug delivery

2015 ◽  
Vol 51 (14) ◽  
pp. 2999-3002 ◽  
Author(s):  
Yin Wang ◽  
Jianwei Du ◽  
Youxiang Wang ◽  
Qiao Jin ◽  
Jian Ji
Keyword(s):  
Drug Delivery ◽  
Acidic Condition ◽  
Ph Responsive ◽  
Intracellular Drug Delivery ◽  
Aggregate Behavior ◽  
Therapy Effect

A novel type of dual pH-responsive supramolecular prodrug micelles based on pillar[5]arene was prepared. It was found that the prodrug micelles could be aggregated upon acidic condition, which led to enhanced accumulation and better therapy effect.

Collagen Nanoparticles in Drug Delivery Systems and Tissue Engineering

2021 ◽  
Vol 11 (23) ◽  
pp. 11369
Author(s):  
Ashni Arun ◽  
Pratyusha Malrautu ◽  
Anindita Laha ◽  
Hongrong Luo ◽  
Seeram Ramakrishna
Keyword(s):  
Drug Delivery ◽  
Tissue Engineering ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Drug Solubility ◽  
Stimuli Responsive ◽  
Preparation Methods ◽  
Nanoparticle Preparation ◽  
Responsive Behavior ◽  
Reduced Toxicity

The versatile natural polymer, collagen, has gained vast attention in biomedicine. Due to its biocompatibility, biodegradability, weak antigenicity, biomimetics and well-known safety profile, it is widely used as a drug, protein and gene carrier, and as a scaffold matrix in tissue engineering. Nanoparticles develop favorable chemical and physical properties such as increased drug half-life, improved hydrophobic drug solubility and controlled and targeted drug release. Their reduced toxicity, controllable characteristics of scaffolds and stimuli-responsive behavior make them suitable in regenerative medicine and tissue engineering. Collagen associates and absorbs nanoparticles leading to significant impacts on their biological functioning in any biofluid. This review will discuss collagen nanoparticle preparation methods and their applications and developments in drug delivery systems and tissue engineering.

scholarly journals Factors Affecting Intracellular Delivery and Release of Hydrophilic Versus Hydrophobic Cargo from Mesoporous Silica Nanoparticles on 2D and 3D Cell Cultures

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 237 ◽  
Author(s):  
Diti Desai ◽  
Malin Åkerfelt ◽  
Neeraj Prabhakar ◽  
Mervi Toriseva ◽  
Tuomas Näreoja ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Mesoporous Silica ◽  
Surface Charge ◽  
Silica Nanoparticles ◽  
Lipid Bilayers ◽  
Mesoporous Silica Nanoparticles ◽  
Cellular Level ◽  
Dependent Manner ◽  
Ethylene Imine ◽  
Intracellular Drug Delivery

Intracellular drug delivery by mesoporous silica nanoparticles (MSNs) carrying hydrophilic and hydrophobic fluorophores as model drug cargo is demonstrated on 2D cellular and 3D tumor organoid level. Two different MSN designs, chosen on the basis of the characteristics of the loaded cargo, were used: MSNs with a surface-grown poly(ethylene imine), PEI, coating only for hydrophobic cargo and MSNs with lipid bilayers covalently coupled to the PEI layer as a diffusion barrier for hydrophilic cargo. First, the effect of hydrophobicity corresponding to loading degree (hydrophobic cargo) as well as surface charge (hydrophilic cargo) on intracellular drug release was studied on the cellular level. All incorporated agents were able to release to varying degrees from the endosomes into the cytoplasm in a loading degree (hydrophobic) or surface charge (hydrophilic) dependent manner as detected by live cell imaging. When administered to organotypic 3D tumor models, the hydrophilic versus hydrophobic cargo-carrying MSNs showed remarkable differences in labeling efficiency, which in this case also corresponds to drug delivery efficacy in 3D. The obtained results could thus indicate design aspects to be taken into account for the development of efficacious intracellular drug delivery systems, especially in the translation from standard 2D culture to more biologically relevant organotypic 3D cultures.

Disulfide crosslinked PEGylated starch micelles as efficient intracellular drug delivery platforms

Soft Matter ◽  
2013 ◽  
Vol 9 (7) ◽  
pp. 2224 ◽  
Author(s):  
Aiping Zhang ◽  
Zhe Zhang ◽  
Fenghua Shi ◽  
Jianxun Ding ◽  
Chunsheng Xiao ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Intracellular Drug Delivery
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