Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers

With the emergence and spread of global antibiotic resistance and the need for searching safer alternatives, there has been resurgence in exploring the use of bacteriophages in the treatment of bacterial infections referred as phage therapy. Although modern phage therapy has come a long way as demon...

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Main Authors: Sandeep Kaur, Anila Kumari, Anjana Kumari Negi, Vikas Galav, Shikha Thakur, Manish Agrawal, Vandana Sharma
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-10-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2021.699054/full
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author Sandeep Kaur
Anila Kumari
Anjana Kumari Negi
Vikas Galav
Shikha Thakur
Manish Agrawal
Vandana Sharma
author_facet Sandeep Kaur
Anila Kumari
Anjana Kumari Negi
Vikas Galav
Shikha Thakur
Manish Agrawal
Vandana Sharma
author_sort Sandeep Kaur
collection DOAJ
description With the emergence and spread of global antibiotic resistance and the need for searching safer alternatives, there has been resurgence in exploring the use of bacteriophages in the treatment of bacterial infections referred as phage therapy. Although modern phage therapy has come a long way as demonstrated by numerous efficacy studies but the fact remains that till date, phage therapy has not received regulatory approval for human use (except for compassionate use).Thus, to hit the clinical market, the roadblocks need to be seriously addressed and gaps mended with modern solution based technologies. Nanotechnology represents one such ideal and powerful tool for overcoming the pharmacological barriers (low stability, poor in-vivo retention, targeted delivery, neutralisation by immune system etc.) of administered phage preparations.In literature, there are many review articles on nanotechnology and bacteriophages but these are primarily focussed on highlighting the use of lytic and temperate phages in different fields of nano-medicine such as nanoprobes, nanosensors, cancer diagnostics, cancer cell targeting, drug delivery through phage receptors, phage display etc. Reviews specifically focused on the use of nanotechnology driven techniques strictly to improve phage therapy are however limited. Moreover, these review if present have primarily focussed on discussing encapsulation as a primary method for improving the stability and retention of phage(s) in the body.With new advances made in the field of nanotechnology, approaches extend from mere encapsulation to recently adopted newer strategies. The present review gives a detailed insight into the more recent strategies which include 1) use of lipid based nano-carriers (liposomes, transfersomes etc.) 2) adopting microfluidic based approach, surface modification methods to further enhance the efficiency and stability of phage loaded liposomes 3) Nano- emulsification approach with integration of microfluidics for producing multiple emulsions (suitable for phage cocktails) with unique control over size, shape and drop morphology 4) Phage loaded nanofibers produced by electro-spinning and advanced core shell nanofibers for immediate, biphasic and delayed release systems and 5) Smart release drug delivery platforms that allow superior control over dosing and phage release as and when required. All these new advances are aimed at creating a suitable housing system for therapeutic bacteriophage preparations while targeting the multiple issues of phage therapy i.e., improving phage stability and titers, improving in-vivo retention times, acting as suitable delivery systems for sustained release at target site of infection, improved penetration into biofilms and protection from immune cell attack. The present review thus aims at giving a complete insight into the recent advances (2010 onwards) related to various nanotechnology based approaches to address the issues pertaining to phage therapy. This is essential for improving the overall therapeutic index and success of phage therapy for future clinical approval.
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spelling doaj.art-4850b24168fe46c4a5a6a3e3436eb2042022-12-21T23:30:05ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-10-011210.3389/fphar.2021.699054699054Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological BarriersSandeep Kaur0Anila Kumari1Anjana Kumari Negi2Vikas Galav3Shikha Thakur4Manish Agrawal5Vandana Sharma6Department of Food Science, Mehr Chand Mahajan DAV College for Women, Chandigarh, IndiaDepartment of Food Science, Mehr Chand Mahajan DAV College for Women, Chandigarh, IndiaDepartment of Biochemistry, Dr. Rajendra Prasad Government Medical College, Himachal Pradesh, IndiaDepartment of Veterinary Pathology, Post Graduate Institute of Veterinary Education and Research (RAJUVAS), Jaipur, IndiaDepartment of Biotechnology, Kumaun University, Uttarakhand, IndiaDepartment of Veterinary Pathology, Post Graduate Institute of Veterinary Education and Research (RAJUVAS), Jaipur, IndiaDepartment of Food Science, Mehr Chand Mahajan DAV College for Women, Chandigarh, IndiaWith the emergence and spread of global antibiotic resistance and the need for searching safer alternatives, there has been resurgence in exploring the use of bacteriophages in the treatment of bacterial infections referred as phage therapy. Although modern phage therapy has come a long way as demonstrated by numerous efficacy studies but the fact remains that till date, phage therapy has not received regulatory approval for human use (except for compassionate use).Thus, to hit the clinical market, the roadblocks need to be seriously addressed and gaps mended with modern solution based technologies. Nanotechnology represents one such ideal and powerful tool for overcoming the pharmacological barriers (low stability, poor in-vivo retention, targeted delivery, neutralisation by immune system etc.) of administered phage preparations.In literature, there are many review articles on nanotechnology and bacteriophages but these are primarily focussed on highlighting the use of lytic and temperate phages in different fields of nano-medicine such as nanoprobes, nanosensors, cancer diagnostics, cancer cell targeting, drug delivery through phage receptors, phage display etc. Reviews specifically focused on the use of nanotechnology driven techniques strictly to improve phage therapy are however limited. Moreover, these review if present have primarily focussed on discussing encapsulation as a primary method for improving the stability and retention of phage(s) in the body.With new advances made in the field of nanotechnology, approaches extend from mere encapsulation to recently adopted newer strategies. The present review gives a detailed insight into the more recent strategies which include 1) use of lipid based nano-carriers (liposomes, transfersomes etc.) 2) adopting microfluidic based approach, surface modification methods to further enhance the efficiency and stability of phage loaded liposomes 3) Nano- emulsification approach with integration of microfluidics for producing multiple emulsions (suitable for phage cocktails) with unique control over size, shape and drop morphology 4) Phage loaded nanofibers produced by electro-spinning and advanced core shell nanofibers for immediate, biphasic and delayed release systems and 5) Smart release drug delivery platforms that allow superior control over dosing and phage release as and when required. All these new advances are aimed at creating a suitable housing system for therapeutic bacteriophage preparations while targeting the multiple issues of phage therapy i.e., improving phage stability and titers, improving in-vivo retention times, acting as suitable delivery systems for sustained release at target site of infection, improved penetration into biofilms and protection from immune cell attack. The present review thus aims at giving a complete insight into the recent advances (2010 onwards) related to various nanotechnology based approaches to address the issues pertaining to phage therapy. This is essential for improving the overall therapeutic index and success of phage therapy for future clinical approval.https://www.frontiersin.org/articles/10.3389/fphar.2021.699054/fullnanotechnologyphage therapynano-emulsificationencapsulationliposomenanofibers
spellingShingle Sandeep Kaur
Anila Kumari
Anjana Kumari Negi
Vikas Galav
Shikha Thakur
Manish Agrawal
Vandana Sharma
Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers
Frontiers in Pharmacology
nanotechnology
phage therapy
nano-emulsification
encapsulation
liposome
nanofibers
title Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers
title_full Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers
title_fullStr Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers
title_full_unstemmed Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers
title_short Nanotechnology Based Approaches in Phage Therapy: Overcoming the Pharmacological Barriers
title_sort nanotechnology based approaches in phage therapy overcoming the pharmacological barriers
topic nanotechnology
phage therapy
nano-emulsification
encapsulation
liposome
nanofibers
url https://www.frontiersin.org/articles/10.3389/fphar.2021.699054/full
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AT vikasgalav nanotechnologybasedapproachesinphagetherapyovercomingthepharmacologicalbarriers
AT shikhathakur nanotechnologybasedapproachesinphagetherapyovercomingthepharmacologicalbarriers
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