Designing nano-carriers smart drug delivery

Designing nano-carriers for smart drug delivery

11:05 AM, 11th July 2016
Designing nano-carriers for smart drug delivery
Ajeet Kaushik, an assistant professor, center of personalized nanomedicine, institute of neuroImmune pharmacology, department of immunology, Herbert Wertheim College of Medicine, Florida International University (FIU), Miami.

In an interaction Ajeet Kaushik, an assistant professor, center of personalized nanomedicine, institute of neuroImmune pharmacology, department of immunology, Herbert Wertheim College of Medicine, Florida International University (FIU), Miami with Chemical Today magazine discusses about his novel research on the development of electro-active magnetic nano-carriers for site-specific on-demand controlled delivery of Anti-HIV drug to prevent neuroAIDS.

Explain in brief about your current research  

My research interest is to investi­gate magneto-electro nanocarriers (ME-NCs) for on-demand site-spe­cific controlled drug delivery across blood-brain-barriers (BBB) for Therapeutics of CNS diseases and the development of electrochem­ical sensing technology for bio­markers detection at point-of-care (POC) application.

Human immunodeficiency virus (HIV) is a deadly infectious disease and a serious disquiet worldwide. Developing best therapeutics for HIV demands multidisciplinary analytical approaches involving smart sensors, imaging agents, diagnostic tools, biomarkers, bio-imaging, affinity agents, smart assaying, disease monitoring, and management systems to develop accessible cost-effective diagno­sis and treatment for HIV patients. Advancements in analysis have proven a significant role in HIV diagnostics and diseases progress monitoring. Food and drug admin­istration (FDA) approved various anti-HIV drugs. The therapeutic effects of those drugs have studied using advanced analytical tools and methods. Guided genes i.e., CRISPER-Cas9/gRNA system is recently investigated to eradicate HIV in latently infected HIV reser­voirs. Unfortunately, these studies were performed either in-vitro or in periphery. HIV infected and latently infected HIV brain reservoirs could not targeted due to negligible trans­migration of therapeutics against HIV across BBB. Therefore, efforts are being made to explore novel analytical science and nanotech­nology for developing strategies to delivery therapeutics across BBB to prevent NeuroAIDS

In the course of my research, I ex­plored various analytical tools and smart nanomaterials for application of developing new biosensing sys­tems and nanomedicines for CNS diseases. Presently my main focus is developing electro-active nano­structures to develop electrochem­ical biosensor and nano-medicine for personalized health care.

My research interests are related to designing smart nano-carries for drug delivery, nano-therapeu­tics for CNS diseases, on-demand site-specific release of Anti-HIV drug to cure neuroAIDS, explor­ing personalized nano-medicines, developing novel tools to recognize & eradicate HIV latent brain reser­voirs, novel tool for HIV incidence using guided RNA (gRNA) nano­technology, bio-nanotechnology, biosensors, point-of-care sensing devices, and related areas of health care monitoring.

What are the advantages of nanomedicines and its usage in your research?

At the Center of Personalized NanoMedicine, Dept of Immunol­ogy, Herbert Wertheim College of Medicine, Florida International Uni­versity, Miami US, we developed “electro-active magnetic nano-car­riers for site-specific on-demand controlled delivery of Anti-HIV drug to prevent neuroAIDS”

What are the benefits and uses of nanomedi­cines?

Nanomedicine with the ability of higher efficacy, no side-effect, site-specific, and therapeutic effect in sustained or on-demand manner to cure targeted diseases are bene­ficial over conventional medicine.

What are the various ma­terials you used to de­velop nanomedicines?

Based on chemical, functional, physical, and structural properties, nanocarriers (NCs) of metal, metal oxides, gels, biopolymer, compos­ites, and core-shell nanostructures are being designed and explored to bind with drugs. The successful release of bind drugs were demon­strated in sustained and externally stimulated on-demand controlled  manner.

At present, developed nanoformu­lations (NFs) i.e., optimized com­bination of NCs and specific drug, tested using in-vitro model and exhibited high therapeutic effect and less adverse effect. Numerous reports confirms that navigation across BBB depends on the prop­erties of NCs and NFs.

Thus exploring properties of NCs and NFs independently is crucial to design an effective therapeutic car­go to cure HIV completely at brain. Though, BBB always prevents the migration of NCs to brain. Surface

science has explored to make NCs surface hydrophobic and to gen­erate functionality on NCs to bind with BBB related specific biomole­cules such as antibody, protein, and enzyme to achieve CNS delivery.

Externally controlled navigation strategy based on magnetic field and ultrasound strategy has recent­ly been demonstrated for transmi­gration of NCs across BBB.

What are the novel an­alytical tools used for your research?

Nano-engineered NCs, highly sensitive technologies, and smart assays are being explored to develop an ideal nanomedicine via improving NCs properties, pharma­cokinetics, and acceptable neuro­behavioral alteration. During virus progression, the dysfunction of related biomarkers and genes have been quantified using sensitive an­alytical assaying namely PCR, and ELISA. Ultrasensitive histopathol­ogy, immonohistipathology, optical florescence imaging have adopted recently to explore the bio-distribu­tion, pathogenesis, and toxicity of both NCs and NFs.

Recently transmission electron microscopy (TEM) with illuminating feature introduced recently to study the distribution on NCs in various organs to explain particle-to-particle interaction and elemental compo­sition of NCs on ageing. Bio-distri­bution and therapeutic effects of contrast agents containing NCs and NFs at periphery and brain are studies using magnetic resonance imaging (MRI). The homeostat effect of NCs in living system also studied using MRI via real time monitoring of contrast exposure.

Explain in brief about smart nanocarriers that have being using for drug delivery

Nanostructures such as A) Poly­meric nanoparticle (PLGA, PLA PBCA); B) Liposomes; C) Polymer­ic micelle; D) Dendrimers; E) Lipid micro & nanoemulsion; F) Solid lipid nanoparticle and G) Inorganic NCs including: (i) Metal & metal oxide nanoparticles; (ii) Carbon nanotubes; (iii) Quantum dots; (iv) Magnetic nanoparticles (MNP) and (v) Core-shell nanoparticles (MENP) are being used to develop nanomedicine.

Among them, MNPs were pur­posed as potentials NCs to prepare effective NFs for the eradication of diseases. MNPs have also explored to develop and smart multifunction­al carrier using layer-by-layer (LBL) method to delivery and release many therapeutic agents. Such developed therapeutic cargo was capable to across BBB under the influence of a magnetic and to release drug in sustained manner for 5 days. Externally controlled on-demand controlled release of anti-HIV drugs was also achieved using MENPs and MNPs.

What were the most chal­lenging issues for your area of research?

Some of the challenging areas were:

• Improvement in biocompatibility and therapeutic effects of nano­medicine,

• Developing personalized nano­medicine combat against CNS diseases,

Promotion of state-of-the art for translation research

Tell us more about your area of work.

I have also studied electrochemi­cal sensing technology during my Ph.D. at National Physical Labo­ratory, India and at BioMEMS and Fabrication system laboratory at Department of electrical computing engineering of Florida Internation­al University, USA in the area of developing nanostructured plat­forms for biosensor to detect target analytes.

The demand for real time health­care monitoring devices is rapidly increasing due to the numerous benefits that this technology offers from a social, scientific, and finan­cial perspective. Portable miniatur­ized analytical devices for disease detection at early stages and for monitoring physiological variables at point-of-care (POC) could be useful to personalize health diag­nostics for appropriate effectual and exact treatment. Since glo­balization and modern lifestyles affect genetic disorder and protein concentration, which are some of the main causes of diseases, these systems are deemed as pioneer technology for the improvement of both global healthcare and health disparities monitoring.

The development of diagnostics tools that are capable of quantify­ing specific biomarkers and of pro­viding health informatics for superi­or treatment strategy, such as POC sensors, are in high demand. The development of novel methods for adequate diagnostic testing at early stage for global healthcare monitor­ing at POC requires the utilization of specific electronic devices that interact with biological samples in order to retrieve indispensable information regarding the patient’s metabolism. I explored nano-en­abling sensing technologies to create wearable electrochemical sensors for POC.

The integration of electrochemi­cal nanosensor with microfluidic system for POC application is still new and exciting to me. Recently, I explored miniaturized electro­chemical immunosensor to detect plasma cortisol of HIV positive. I explored my knowledge of analyti­cal chemistry, nanotechnology, and electrochemistry to understand electrochemical behavior of tumor and single cell. My contribution in the area of developing BioMEMS to trap multi-cell spheroid for 3D monitoring for diagnosis and chip-based electrochemical sensing device for single cell nanotoxicity detection can be judged by various publication.

I would recommend to explore new electrochemical nano-immuno­sensing technologies specifically development of lab-on-a-chip integrated with microfluidic system to detect physiological variables for personalized diagnostics at POC. Such sensing platforms may have the potential to be integrated into a wearable system for online and continuous monitoring of any target analyte at pico/nano levels at POC as a function of one’s environment.

© Chemical Today Magazine


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