Recent updates in utilizing prodrugs in drug delivery (2013–2015)

ABSTRACT

Introduction: Utilizing the prodrug approach as a method to overcome various pharmaceutical and pharmacokinetic barriers to drug delivery is significantly accelerating and achieving successes. In contrast to the older traditional prodrugs which suffer from decreased bioavailability and a high profile of side effects, due to activation at undesired sites, the targeted prodrug approach utilizes delivery systems to improve delivery for a wide range of therapeutics including anti-cancer, anti-bacterial and anti-inflammatory drugs.

Areas covered: Recent updates in utilization of prodrugs in drug delivery between 2013 and 2015 are discussed. Targeted prodrugs against cancer, solid tumors, microbial infections, inflammation and other diseases using advanced delivery systems such as theranostic approaches, siRNA, DOX immunoconjugate, C 60-ser carrier vector, biotinylated prodrug, human serum albumin (HSA) carrier and others are presented.

Expert opinion: Recent research efforts have been directed at developing targeted prodrugs to replace the classical prodrugs. The use of this approach has accelerated following the emergence of encouraging results from several studies on targeted prodrugs that have highlighted their higher efficiency and improved safety profiles.

Targeted prodrug delivery is now considered more than a chemical modification method. It is an applicable and promising approach and, in the future, better knowledge and wide application of this approach may be attained which may pave the way for more forward-thinking and creative techniques.

KEYWORDS:

• Ciprofloxacin prodrugs
• doxorubicin prodrugs
• gemcitabine prodrugs
• GDEPT
• paclitaxel prodrugs
• platinum prodrugs
• siRNA
• SN-38 prodrugs
• targeted drug delivery

Article highlights

• Drug delivery systems (DDSs) are commonly used to overcome barriers. Different DDSs are investigated and widely used in spite of some disadvantages associated with their use.

• Chemotherapeutic agents such as paclitaxel, doxorubicin, gemcitabine (GMC), platinum compounds and SN-38 are among the most benefited drugs from the prodrugs strategies and drug delivery targeting.

• The theranostic (therapy and diagnostics) DDS, which has targeting and reporting abilities, has shown some successes in cancer therapy through the use of GMC-loaded coumarin moiety coupled with biotin as a targeting ligand.

• Some nitroaromatic prodrugs are a successful example for utilizing the gene-directed enzyme prodrug therapy approach.

• Immunoconjugate, C₆₀-ser carrier vector and siRNA approaches are recently used and showed promising results. They are targeted for cancer therapy.

• Novel prodrugs of antimicrobial agents such as ribavirin and ciprofloxacin have showed advantageous over their parent drugs.

• Brain-targeted drug delivery using ascorbic acid as a carrier to improve drug’s blood–brain barrier permeation properties has shown success in delivering ibuprofen prodrugs to the brain.

This box summarizes key points contained in the article.

Acknowledgement

Special thanks is also given to Prof. Mustafa Khamis for technical assistance.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

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