Abstract 6257: DPX™ platform for drug delivery: Evaluation of lymph node-targeted delivery of immunomodulatory agents in DPX

Author(s):  
Heather Torrey ◽  
Ava Vila-Leahey ◽  
Yuchen Cen ◽  
Danielle MacKay ◽  
Alecia MacKay ◽  
...  
Author(s):  
Susan N. Thomas

Immunotherapy-based approaches for cancer treatment are of increasing clinical interest. Principles of drug delivery and the emerging field of material design for immunomodulation might hold significant promise for novel approaches in cancer immunotherapy since biomaterials engineering strategies enable enhanced delivery of immune modulatory agents to tissues and cells of the immune system1. One tissue of significant clinical interest in a cancer setting is the tumor-draining lymph node (TDLN), which participates in cancer progression by enabling both metastatic dissemination as well as tumor-induced immune escape. Hence, the TDLN represents a novel target for drug delivery schemes for cancer immunotherapy. We hypothesize that targeted delivery of adjuvants (Adjs) to the TDLN using a biomaterials-based approach might promote antitumor immunity and hinder tumor growth.


Author(s):  
G D Chandrethiya ◽  
P K Shelat ◽  
M N Zaveri

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.  


2020 ◽  
Vol 21 (11) ◽  
pp. 902-909
Author(s):  
Jingxin Zhang ◽  
Weiyue Shi ◽  
Gangqiang Xue ◽  
Qiang Ma ◽  
Haixin Cui ◽  
...  

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.


2020 ◽  
Vol 17 ◽  
Author(s):  
Neeraj Mittal ◽  
Varun Garg ◽  
Sanjay Kumar Bhadada ◽  
O. P. Katare

: 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.


2020 ◽  
Vol 17 (10) ◽  
pp. 911-924
Author(s):  
Rohitas Deshmukh

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.


2019 ◽  
Vol 18 (15) ◽  
pp. 2078-2092 ◽  
Author(s):  
Mala Sharma ◽  
Chitranshu Pandey ◽  
Neha Sharma ◽  
Mohammad A. Kamal ◽  
Usman Sayeed ◽  
...  

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.


Author(s):  
Feng Wu ◽  
Fei Qiu ◽  
Siew Anthony Wai-Keong ◽  
Yong Diao

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.


The Analyst ◽  
2017 ◽  
Vol 142 (4) ◽  
pp. 649-659 ◽  
Author(s):  
Ashley E. Ross ◽  
Maura C. Belanger ◽  
Jacob F. Woodroof ◽  
Rebecca R. Pompano

We present the first microfluidic platform for local stimulation of lymph node tissue slices and demonstrate targeted delivery of a model therapeutic.


2021 ◽  
pp. 153537022110107
Author(s):  
Noah Trac ◽  
Eun Ji Chung

The lymph nodes are major sites of cancer metastasis and immune activity, and thus represent important clinical targets. Although not as well-studied compared to subcutaneous administration, intravenous drug delivery is advantageous for lymph node delivery as it is commonly practiced in the clinic and has the potential to deliver therapeutics systemically to all lymph nodes. However, rapid clearance by the mononuclear phagocyte system, tight junctions of the blood vascular endothelium, and the collagenous matrix of the interstitium can limit the efficiency of lymph node drug delivery, which has prompted research into the design of nanoparticle-based drug delivery systems. In this mini review, we describe the physiological and biological barriers to lymph node targeting, how they inform nanoparticle design, and discuss the future outlook of lymph node targeting.


Materials ◽  
2021 ◽  
Vol 14 (11) ◽  
pp. 3083
Author(s):  
Cristiana Maria Grapa ◽  
Lucian Mocan ◽  
Dana Crisan ◽  
Mira Florea ◽  
Teodora Mocan

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.


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