Emerging advances in P-glycoprotein inhibitory nanomaterials for drug delivery

ABSTRACT

Introduction: P-glycoprotein 1 (P-gp) pumps out many foreign/toxic substances out of the cells, including intracellular drugs, causing multidrug resistance (MDR) and chemotherapy failure. It remains quite a challenge to inhibit P-gp to combat MDR and improve cellular bioavailability since it requires efficient inhibitors along with adequate formulation strategy. Lately, nanocarriers are gaining much attention and form an attractive platform for delivering drugs into cells. Therefore, nanomaterials act as direct inhibitors of P-gp will be an attractive alternative to overcome MDR.

Area covered: This paper reviews the most recent advances on those nanomaterials that are currently in the developmental stage and has proven useful to treat P-gp involved MDR. Also, we emphasize those emerging multifunctional nanomaterials that can construct ‘smart’ carriers for both tumor targeting and P-gp inhibition. Furthermore, the mechanisms behind P-gp inhibition and the nanoformulation strategies for drug delivery are also discussed.

Expert opinion: In light of these updated reports, this review here seeks to suggest an alternative for the chemoresistant cases, and also bring about new thoughts on tackling P-gp concerned drug delivery issues. New advances in nanomaterials with P-gp inhibition are expected to broaden nanopharmaceutics and traditional chemotherapy applications in the coming years.

KEYWORDS:

• Multidrug resistance
• chemotherapy
• P-glycoprotein inhibitor
• nanomaterials
• drug delivery

Article highlights

• 1. Combination therapy of chemotherapeutics and P-gp inhibitors is a meaningful solution to combat chemoresistance.

• 2. By the P-gp inhibition property and nanoplatform self-assembly ability, P-gp inhibitory nanomaterials could easily formulate chemotherapeutics and combat P-gp efflux.

• 3. Derivatives of classic P-gp inhibitory nanomaterials, such as polymeric conjugates, drug conjugates, and stimuli-responsive analogs, are prevalent to optimize formed nanocarriers’ stability, increase the drug loading, prevent premature drug release, and “smartly” deliver therapeutics.

• 4. Some MMP-sensitive nanomaterials were found to be able to inhibit the P-gp mediated drug efflux.

• 5. Soluplus, an FDA approved pharmaceutical excipient, is an intrinsic P-gp inhibitor, and account for the improved oral bioavailability and chemosensitization.

Investigational drug discovery for AD should include both topical and systemic medicine. Objective scientific documentation of drug efficacy and adverse effects must be carried out.

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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.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China (NSFC, Grant No. 81803443) and the start-up funds from the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University.