Drug Delivery: Targeted Delivery with Monoclonal Antibodies

2013 ◽  
pp. 1194-1210
Keyword(s):  
Drug Delivery ◽  
Monoclonal Antibodies ◽  
Targeted Delivery

Development and Characterization Colchicine-Loaded PEGylated Gelatin Nanoparticles for Targeted Delivery to Tumor

2013 ◽  
Vol 6 (2) ◽  
pp. 2058-2063
Author(s):  
G D Chandrethiya ◽  
P K Shelat ◽  
M N Zaveri
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
High Performance ◽  
Entrapment Efficiency ◽  
Stability Study ◽  
Spherical Particles ◽  
Precipitation Method ◽  
Antitumoral Activity ◽  
Gelatin Nanoparticles

PEGylated gelatin nanoparticles loaded with colchicine were prepared by ethanol precipitation method. Poly-(ethylene glycol)-5000-monomethylether (MPEG 5000), a hydrophilic polymer, was used to pegylate gelatin.  Gluteraldehyde was used as cross-linking agent. To obtain a high quality product, major formulation parameters were optimized.  Spherical particles with mean particles of 193 nm were measured by a Malvern particle size analyzer. Entrapment efficiency was found to be 71.7 ± 1.4% and determined with reverse phase high performance liquid charomatography (RP-HPLC). The in vitro drug release study was performed by dialysis bag method for a period of 168 hours. Lyophilizaton study showed sucrose at lower concentrations proved the best cryoprotectant for this formulation.  Stability study revealed that lyophilized nanoparticles were equally effective (p < 0.05) after one year of storage at 2-8°C with ambient humidity. In vitro antitumoral activity was accessed using the MCF-7 cell line by MTT assay.  The IC50 value was found to be 0.034 μg/ml for the prepared formulation. The results indicate that PEGylated gelatin nanoparticles could be utilized as a potential drug delivery for targeted drug delivery of tumors.  

PERSPECTIVES OF APPLICATION OF ANTIBODIES AGAINST ENDOGLIN (CD105) FOR VISUALIZATION AND ANTI-ANGIOGENE THERAPY OF TUMORS

2018 ◽  
Vol 64 (4) ◽  
pp. 504-507
Author(s):  
Vladimir Klimovich ◽  
Natalya Vartanyan ◽  
Anastasiya Stolbovaya ◽  
Lidiya Terekhina ◽  
Olga Shashkova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Monoclonal Antibodies ◽  
Human Plasma ◽  
Vascular Endothelium ◽  
Immune Complexes ◽  
Targeted Delivery ◽  
Biological Fluids ◽  
Therapeutic Drugs ◽  
Cultured Endothelial Cells ◽  
Hybridoma Technology

During last years monoclonal antibodies (MAB) directed against vascular endothelium markers demonstrated their efficiency for visualization and targeted delivery of therapeutic drugs to tumors. Endoglin (CD105) which serves as a key element that determines endothelial cells quiescence or activation is one of such markers. Endoglin is highly expressed on the vascular endothelium of growing tumors. A first panel of MAB against endoglin in our country was produced at the hybridoma technology laboratory of RRC RST named after A.M. Granov. On the basis of these MAB ELISA was created allowing detection of endoglin in human plasma and other biological fluids. Several MAB had been shown to bind endoglin on the membrane of the cultured endothelial cells and to persist there for several hours. During the first 30 min after binding some of the immune complexes “endoglin-MAB” were internalized into the cytoplasm and were found included in the endosomes. In future these MAB can be used to create the reagents for the addressed delivery of isotope tags both on the membrane and into the cytoplasm of endothelial cells.

Improved Therapeutic Efficacy of Topotecan Against A549 Lung Cancer Cells with Folate-targeted Topotecan Liposomes

2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Drug Delivery ◽  
Cancer Cells ◽  
Targeted Delivery ◽  
Therapeutic Efficacy ◽  
Drug Delivery Systems ◽  
Lung Tumor ◽  
A549 Cells ◽  
Delivery Systems ◽  
Lung Cancer Cells

Background: Among all cancers, lung cancer has high mortality among patients in most of the countries in the world. Targeted delivery of anticancer drugs can significantly reduce the side effects and dramatically improve the effects of the treatment. Folate, a suitable ligand, can be modified to the surface of tumor-selective drug delivery systems because it can selectively bind to the folate receptor, which is highly expressed on the surface of lung tumor cells. Objective: This study aimed to construct a kind of folate-targeted topotecan liposomes for investigating their efficacy and mechanism of action in the treatment of lung cancer in preclinical models. Methods: We conjugated topotecan liposomes with folate, and the liposomes were characterized by particle size, entrapment efficiency, cytotoxicity to A549 cells and in vitro release profile. Technical evaluations were performed on lung cancer A549 cells and xenografted A549 cancer cells in female nude mice, and the pharmacokinetics of the drug were evaluated in female SD rats. Results: The folate-targeted topotecan liposomes were proven to show effectiveness in targeting lung tumors. The anti-tumor effects of these liposomes were demonstrated by the decreased tumor volume and improved therapeutic efficacy. The folate-targeted topotecan liposomes also lengthened the topotecan blood circulation time. Conclusion: The folate-targeted topotecan liposomes are effective drug delivery systems and can be easily modified with folate, enabling the targeted liposomes to deliver topotecan to lung cancer cells and kill them, which could be used as potential carriers for lung chemotherapy.

Role of novel drug delivery systems in coronavirus disease-2019 (covid-19): time to act now

2020 ◽  
Vol 17 ◽  
Author(s):  
Neeraj Mittal ◽  
Varun Garg ◽  
Sanjay Kumar Bhadada ◽  
O. P. Katare
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Delivery Systems ◽  
World Health ◽  
Ongoing Research ◽  
Standard Drug ◽  
Corona Virus ◽  
Novel Drug

: The corona virus disease 2019 (COVID-19) has found its roots from Wuhan (China). COVID-19 is caused by a novel corona virus SARS-CoV2, previously named as 2019-nCoV. COVID-19 has spread across the globe and declared as pandemic by World health organization (WHO) on 11th March, 2020. Currently, there is no standard drug or vaccine available for the treatment, so repurposing of existing drugs is the only solution. Novel drug delivery systems (NDDS) will be boon for the repurposing of drugs. The role of various NDDS in repurposing of existing drugs for treatment of various viral diseases and their relevance in COVID-19 has discussed in this paper. It focuses on the currently ongoing research in the implementation of NDDS in COVID-19. Moreover it describes the role of NDDS in vaccine development for COVID-19. This paper also emphasizes how NDDS will help to develop the improved delivery systems (dosage forms) of existing therapeutic agents and also explore the new insights to find out the void spaces for a potential targeted delivery. So in these tough times, NDDS and nanotechnology can be a safeguard to humanity.

Bridging the Gap of Drug Delivery in Colon Cancer: The Role of Chitosan and Pectin Based Nanocarriers System

2020 ◽  
Vol 17 (10) ◽  
pp. 911-924
Author(s):  
Rohitas Deshmukh
Keyword(s):  
Drug Delivery ◽  
Colon Cancer ◽  
Targeted Drug Delivery ◽  
Targeted Delivery ◽  
Therapeutic Agent ◽  
Therapeutic Agents ◽  
Delivery Systems ◽  
Target Tissue ◽  
Polymer Carriers

Colon cancer is one of the most prevalent diseases, and traditional chemotherapy has not been proven beneficial in its treatment. It ranks second in terms of mortality due to all cancers for all ages. Lack of selectivity and poor biodistribution are the biggest challenges in developing potential therapeutic agents for the treatment of colon cancer. Nanoparticles hold enormous prospects as an effective drug delivery system. The delivery systems employing the use of polymers, such as chitosan and pectin as carrier molecules, ensure the maximum absorption of the drug, reduce unwanted side effects and also offer protection to the therapeutic agent from quick clearance or degradation, thus allowing an increased amount of the drug to reach the target tissue or cells. In this systematic review of published literature, the author aimed to assess the role of chitosan and pectin as polymer-carriers in colon targeted delivery of drugs in colon cancer therapy. This review summarizes the various studies employing the use of chitosan and pectin in colon targeted drug delivery systems.

Cancer Nanotechnology-An Excursion on Drug Delivery Systems

2019 ◽  
Vol 18 (15) ◽  
pp. 2078-2092 ◽  
Author(s):  
Mala Sharma ◽  
Chitranshu Pandey ◽  
Neha Sharma ◽  
Mohammad A. Kamal ◽  
Usman Sayeed ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Drug Delivery Systems ◽  
Cancer Chemoprevention ◽  
Delivery Systems ◽  
Nanostructured Lipid Carrier ◽  
Nanodrug Delivery ◽  
Drug Conjugates ◽  
Drug Nanoparticles ◽  
Cancer Nanotechnology

Background: Nanotechnology pictures a breakthrough in the domain of cancer therapy owing to its novel properties and functions. This technology is quite amendable as it allows the scientists to engineer drug nanoparticles of dimensions 10nm – 500nm permitting them to pass via leaky vasculature of tumorigenic microenvironment with higher specificity, reduced cytotoxicity and effective release without any after effects. The central part of the review zooms onto the role of nanoparticles and their targeted delivery for the cure of cancer. Methods: The novel and various versatile nanoparticle platforms viz. polymeric (drug-conjugates, micelles, dendrimers), Lipid-based (liposomes, solid nanoparticle, nanostructured lipid carrier, lipid-polymer hybrid), and stimuli-sensitive (thermoresponsive, ultrasound, pH-responsive, hydrogel) etc. have been designed for a persistent, précised nanodrug delivery and the co-delivery of collegial drug conjugates leading to the formation of safer release of myriad of drugs for cancer chemoprevention. Results: The review concerns about tracing and detailing the drug delivery systems of cancer nanotechnology. Conclusion: Nanotechnology is bestowed with the design, depiction, fabrication, and application of nanostructures, and devices with their controlled delivery together with the imaging of the selected target site and drug release at the specific site of action.

The Smart Dual-Stimuli Responsive Nanoparticles for Controlled AntiTumor Drug Release and Cancer Therapy

2020 ◽  
Vol 20 ◽  
Author(s):  
Feng Wu ◽  
Fei Qiu ◽  
Siew Anthony Wai-Keong ◽  
Yong Diao
Keyword(s):  
Drug Delivery ◽  
Cancer Therapy ◽  
Drug Release ◽  
Targeted Delivery ◽  
Relevant Information ◽  
Therapeutic Effects ◽  
Stimuli Responsive ◽  
Control Effect ◽  
Chemotherapy Drugs ◽  
Excellent Control

Background: In recent years, the emergence of stimuli-responsive nanoparticles makes drug delivery more efficient. As an intelligent and effective targeted delivery platform, it can reduce the side effects generated during drug transportation while enhancing the treatment efficacy. The stimuli-responsive nanoparticles can respond to different stimuli at corresponding times and locations to deliver and release their drugs and associated therapeutic effects. Objective: This review aims to inform researchers on the latest advances in the application of dual-stimuli responsive nanoparticles in precise drug delivery, with special attention to their design, drug release properties, and therapeutic effects. Syntheses of nanoparticles with simultaneous or sequential responses to two or more stimuli (pH-redox, pH-light, redoxlight, temperature-magnetic, pH-redox-temperature, redox-enzyme-light, etc.) and the applications of such responsivity properties for drugs control and release have become a hot topic of recent research. Methods: A database of relevant information for the production of this review was sourced, screened and analyzed from Pubmed, Web of Science, SciFinder by searching for the following keywords: “dual-stimuli responsive”, “controlled release”, “cancer therapy”, “synergistic treatment”. Results: Notably, the nanoparticles with dual-stimuli responsive function have an excellent control effect on drug delivery and release, playing a crucial part in the treatment of tumors. They can improve the encapsulation and delivery efficiency of hydrophobic chemotherapy drugs, combine chemo-photothermal therapies, apply imaging function in the diagnosis of tumors and even conduct multi-drugs delivery to overcome multi-drugs resistance (MDR). Conclusion: With the development of smart dual-stimuli responsive nanoparticles, cancer treatment methods will become more diverse and effective. All the stimuli-responsive nanoparticles functionalities exhibited their characteristics individually within the single nanosystem.

scholarly journals Biomarkers in Pancreatic Cancer as Analytic Targets for Nanomediated Imaging and Therapy

Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 3083
Author(s):  
Cristiana Maria Grapa ◽  
Lucian Mocan ◽  
Dana Crisan ◽  
Mira Florea ◽  
Teodora Mocan
Keyword(s):  
Drug Delivery ◽  
Pancreatic Cancer ◽  
Targeted Delivery ◽  
Drug Toxicity ◽  
Treatment Options ◽  
Tumor Stroma ◽  
Chemotherapy Response ◽  
Rising Incidence ◽  
Tumor Accumulation ◽  
Accumulation Ability

As the increase in therapeutic and imaging technologies is swiftly improving survival chances for cancer patients, pancreatic cancer (PC) still has a grim prognosis and a rising incidence. Practically everything distinguishing for this type of malignancy makes it challenging to treat: no approved method for early detection, extended asymptomatic state, limited treatment options, poor chemotherapy response and dense tumor stroma that impedes drug delivery. We provide a narrative review of our main findings in the field of nanoparticle directed treatment for PC, with a focus on biomarker targeted delivery. By reducing drug toxicity, increasing their tumor accumulation, ability to modulate tumor microenvironment and even improve imaging contrast, it seems that nanotechnology may one day give hope for better outcome in pancreatic cancer. Further conjugating nanoparticles with biomarkers that are overexpressed amplifies the benefits mentioned, with potential increase in survival and treatment response.

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.

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