Peptide- and Aptamer-Functionalized Nanovectors for Targeted Delivery of Therapeutics

2009 ◽  
Vol 131 (7) ◽  
Author(s):  
Todd O. Pangburn ◽  
Matthew A. Petersen ◽  
Brett Waybrant ◽  
Maroof M. Adil ◽  
Efrosini Kokkoli
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Drug Delivery Vehicles ◽  
Delivery Vector ◽  
Current State ◽  
Dna Strands ◽  
Delivery Vehicles

Targeted delivery of therapeutics is an area of vigorous research, and peptide- and aptamer-functionalized nanovectors are a promising class of targeted delivery vehicles. Both peptide- and aptamer-targeting ligands can be readily designed to bind a target selectively with high affinity, and more importantly are molecules accessible by chemical synthesis and relatively compact compared with antibodies and full proteins. The multitude of peptide ligands that have been used for targeted delivery are covered in this review, with discussion of binding selectivity and targeting performance for these peptide sequences where possible. Aptamers are RNA or DNA strands evolutionarily engineered to specifically bind a chosen target. Although use of aptamers in targeted delivery is a relatively new avenue of research, the current state of the field is covered and promises of future advances in this area are highlighted. Liposomes, the classic drug delivery vector, and polymeric nanovectors functionalized with peptide or aptamer binding ligands will be discussed in this review, with the exclusion of other drug delivery vehicles. Targeted delivery of therapeutics, from DNA to classic small molecule drugs to protein therapeutics, by these targeted nanovectors is reviewed with coverage of both in vitro and in vivo deliveries. This is an exciting and dynamic area of research and this review seeks to discuss its broad scope.

Novel Phospholipid-Based Labrasol Nanomicelles Loaded Flavonoids for Oral Delivery with Enhanced Penetration and Anti-Brain Tumor Efficiency

2020 ◽  
Vol 17 (3) ◽  
pp. 229-245
Author(s):  
Gang Wang ◽  
Junjie Wang ◽  
Rui Guan
Keyword(s):  
Drug Delivery ◽  
Brain Tumor ◽  
Oral Delivery ◽  
Safe Delivery ◽  
Drug Delivery Vehicles ◽  
Therapeutic Benefits ◽  
Delivery Vehicles ◽  
The Brain

Background: Owing to the rich anticancer properties of flavonoids, there is a need for their incorporation into drug delivery vehicles like nanomicelles for safe delivery of the drug into the brain tumor microenvironment. Objective: This study, therefore, aimed to prepare the phospholipid-based Labrasol/Pluronic F68 modified nano micelles loaded with flavonoids (Nano-flavonoids) for the delivery of the drug to the target brain tumor. Methods: Myricetin, quercetin and fisetin were selected as the initial drugs to evaluate the biodistribution and acute toxicity of the drug delivery vehicles in rats with implanted C6 glioma tumors after oral administration, while the uptake, retention, release in human intestinal Caco-2 cells and the effect on the brain endothelial barrier were investigated in Human Brain Microvascular Endothelial Cells (HBMECs). Results: The results demonstrated that nano-flavonoids loaded with myricetin showed more evenly distributed targeting tissues and enhanced anti-tumor efficiency in vivo without significant cytotoxicity to Caco-2 cells and alteration in the Trans Epithelial Electric Resistance (TEER). There was no pathological evidence of renal, hepatic or other organs dysfunction after the administration of nanoflavonoids, which showed no significant influence on cytotoxicity to Caco-2 cells. Conclusion: In conclusion, Labrasol/F68-NMs loaded with MYR and quercetin could enhance antiglioma effect in vitro and in vivo, which may be better tools for medical therapy, while the pharmacokinetics and pharmacodynamics of nano-flavonoids may ensure optimal therapeutic benefits.

scholarly journals Biodistribution and Pharmacokinectics of Liposomes and Exosomes in a Mouse Model of Sepsis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 427
Author(s):  
Amin Mirzaaghasi ◽  
Yunho Han ◽  
So-Hee Ahn ◽  
Chulhee Choi ◽  
Ji-Ho Park
Keyword(s):  
Drug Delivery ◽  
Therapeutic Potential ◽  
Hek293t Cell ◽  
Biological Properties ◽  
Context Analysis ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles ◽  
Diseased State ◽  
Sepsis And Septic Shock

Exosomes have attracted considerable attention as drug delivery vehicles because their biological properties can be utilized for selective delivery of therapeutic cargoes to disease sites. In this context, analysis of the in vivo behaviors of exosomes in a diseased state is required to maximize their therapeutic potential as drug delivery vehicles. In this study, we investigated biodistribution and pharmacokinetics of HEK293T cell-derived exosomes and PEGylated liposomes, their synthetic counterparts, into healthy and sepsis mice. We found that biodistribution and pharmacokinetics of exosomes were significantly affected by pathophysiological conditions of sepsis compared to those of liposomes. In the sepsis mice, a substantial number of exosomes were found in the lung after intravenous injection, and their prolonged blood residence was observed due to the liver dysfunction. However, liposomes did not show such sepsis-specific effects significantly. These results demonstrate that exosome-based therapeutics can be developed to manage sepsis and septic shock by virtue of their sepsis-specific in vivo behaviors.

scholarly journals Mechanisms and Pharmaceutical Action of Lipid Nanoformulation of Natural Bioactive Compounds as Efficient Delivery Systems in the Therapy of Osteoarthritis

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1108
Author(s):  
Oana Craciunescu ◽  
Madalina Icriverzi ◽  
Paula Ecaterina Florian ◽  
Anca Roseanu ◽  
Mihaela Trif
Keyword(s):  
Drug Delivery ◽  
Bioactive Compounds ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
Joint Disease ◽  
Duration Of Action ◽  
Immune System Activation

Osteoarthritis (OA) is a degenerative joint disease. An objective of the nanomedicine and drug delivery systems field is to design suitable pharmaceutical nanocarriers with controllable properties for drug delivery and site-specific targeting, in order to achieve greater efficacy and minimal toxicity, compared to the conventional drugs. The aim of this review is to present recent data on natural bioactive compounds with anti-inflammatory properties and efficacy in the treatment of OA, their formulation in lipid nanostructured carriers, mainly liposomes, as controlled release systems and the possibility to be intra-articularly (IA) administered. The literature regarding glycosaminoglycans, proteins, polyphenols and their ability to modify the cell response and mechanisms of action in different models of inflammation are reviewed. The advantages and limits of using lipid nanoformulations as drug delivery systems in OA treatment and the suitable route of administration are also discussed. Liposomes containing glycosaminoglycans presented good biocompatibility, lack of immune system activation, targeted delivery of bioactive compounds to the site of action, protection and efficiency of the encapsulated material, and prolonged duration of action, being highly recommended as controlled delivery systems in OA therapy through IA administration. Lipid nanoformulations of polyphenols were tested both in vivo and in vitro models that mimic OA conditions after IA or other routes of administration, recommending their clinical application.

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.

scholarly journals Well-defined single polymer nanoparticles for the antibody-targeted delivery of chemotherapeutic agents

2015 ◽  
Vol 6 (8) ◽  
pp. 1286-1299 ◽  
Author(s):  
D. D. Lane ◽  
D. Y. Chiu ◽  
F. Y. Su ◽  
S. Srinivasan ◽  
H. B. Kern ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Raft Polymerization ◽  
Chemotherapeutic Agents ◽  
Polymer Nanoparticles ◽  
Drug Delivery Vehicles ◽  
Molecular Weights ◽  
Delivery Vehicles ◽  
Targeted Drug

Second generation polymeric brushes with molecular weights in excess of 106 Da were synthesize via RAFT polymerization for use as antibody targeted drug delivery vehicles.

scholarly journals Cryo-shocked cancer cells for targeted drug delivery and vaccination

2020 ◽  
Vol 6 (50) ◽  
pp. eabc3013
Author(s):  
Tianyuan Ci ◽  
Hongjun Li ◽  
Guojun Chen ◽  
Zejun Wang ◽  
Jinqiang Wang ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Cancer Cells ◽  
Liquid Nitrogen ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Myeloid Leukemia ◽  
Live Cells ◽  
Simple Method ◽  
Drug Delivery Vehicles ◽  
Delivery Vehicles

Live cells have been vastly engineered into drug delivery vehicles to leverage their targeting capability and cargo release behavior. Here, we describe a simple method to obtain therapeutics-containing “dead cells” by shocking live cancer cells in liquid nitrogen to eliminate pathogenicity while preserving their major structure and chemotaxis toward the lesion site. In an acute myeloid leukemia (AML) mouse model, we demonstrated that the liquid nitrogen–treated AML cells (LNT cells) can augment targeted delivery of doxorubicin (DOX) toward the bone marrow. Moreover, LNT cells serve as a cancer vaccine and promote antitumor immune responses that prolong the survival of tumor-bearing mice. Preimmunization with LNT cells along with an adjuvant also protected healthy mice from AML cell challenge.

scholarly journals A supramolecular platform for controlling and optimizing molecular architectures of siRNA targeted delivery vehicles

2020 ◽  
Vol 6 (31) ◽  
pp. eabc2148
Author(s):  
Yuting Wen ◽  
Hongzhen Bai ◽  
Jingling Zhu ◽  
Xia Song ◽  
Guping Tang ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Targeted Delivery ◽  
Tumor Therapy ◽  
Sirna Delivery ◽  
Targeted Gene Delivery ◽  
Delivery Vehicles ◽  
Molecular Architectures ◽  
Host Polymer

It requires multistep synthesis and conjugation processes to incorporate multifunctionalities into a polyplex gene vehicle to overcome numerous hurdles during gene delivery. Here, we describe a supramolecular platform to precisely control, screen, and optimize molecular architectures of siRNA targeted delivery vehicles, which is based on rationally designed host-guest complexation between a β-cyclodextrin–based cationic host polymer and a library of guest polymers with various PEG shape and size, and various density of ligands. The host polymer is responsible to load/unload siRNA, while the guest polymer is responsible to shield the vehicles from nonspecific cellular uptake, to prolong their circulation time, and to target tumor cells. A series of precisely controlled molecular architectures through a simple assembly process allow for a rapid optimization of siRNA delivery vehicles in vitro and in vivo for therapeutic siRNA-Bcl2 delivery and tumor therapy, indicating the platform is a powerful screening tool for targeted gene delivery vehicles.

scholarly journals FORMULATION OF NANOPARTICLES OF TELMISARTAN INCORPORATED IN CARBOXYMETHYLCHITOSAN FOR THE BETTER DRUG DELIVERY AND ENHANCED BIOAVAILABILITY

2017 ◽  
Vol 10 (9) ◽  
pp. 236
Author(s):  
Upasana Yadav ◽  
Angshuman Ray Chowdhuri ◽  
Sumanta Kumar Sahu ◽  
Nuzhat Husain ◽  
Qamar Rehman
Keyword(s):  
Electron Microscopy ◽  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Loading ◽  
Water Soluble ◽  
Bioavailability Enhancement ◽  
Water Soluble Drug ◽  
Efficient Option

  Objective: In this study, we have made an attempt to the developed formulation of nanoparticles (NPs) of telmisartan (TLM) incorporated in carboxymethyl chitosan (CMCS) for the better drug delivery and enhanced bioavailability.Materials and Methods: The NPs size and morphology were investigated by high-resolution transmission electron microscopy and field emission scanning electron microscopy, respectively. The crystal structures and surface functional groups were analyzed using X-ray diffraction pattern, and Fourier transform infrared spectroscopy, respectively.Results: To increase the solubility of TLM by targeted delivery of the drug through polymeric NPs is an alternative efficient, option for increasing the solubility. TLM nanosuspension powders were successfully formulated for dissolution and bioavailability enhancement of the drug. We focused on evaluating the influence of particle size and crystalline state on the in vitro and in vivo performance of TLM.Conclusion: In summary, we have developed a new approach toward the delivery of poorly water-soluble drug TLM by CMCS NPs. The particles having a good drug loading content and drug encapsulation efficiency. The cytotoxicity of the synthesized NPs is also very less.

scholarly journals Nano-Biomimetic Drug Delivery Vehicles: Potential Approaches for COVID-19 Treatment

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5952
Author(s):  
Bwalya A. Witika ◽  
Pedzisai A. Makoni ◽  
Larry L. Mweetwa ◽  
Pascal V. Ntemi ◽  
Melissa T. R. Chikukwa ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Charge Composition ◽  
Drug Delivery Vehicles ◽  
Therapeutic Outcomes ◽  
Delivery Vehicles ◽  
The Impact

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.

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