Current strategies for oral delivery of BCS IV drug nanocrystals: challenges, solutions and future trends

ABSTRACT

Introduction

Oral absorption of BCS IV drug benefits little from improved dissolution. Therefore, the absorption of BCS IV drug nanocrystals ‘as a whole’ strategy is preferred, and structural modification of nanocrystals is required. Surface modification helps the nanocrystals maintain particle structure before drug dissolution is needed, thus enhancing the oral absorption of BCS IV drugs and promoting therapeutic effect. Here, the main challenges and solutions of oral BCS IV drug nanocrystals delivery are discussed. Moreover, strategies for nanocrystal surface modification that facilitates oral bioavailability of BCS IV drugs are highlighted, and provide insights for the innovation in oral drug delivery.

Areas covered

Promising size, shape, and surface modification of nanocrystals have gained interests for application in oral BCS IV drugs.

Expert opinion

Nanocrystal surface modification is a feasible method to maintain the structural integrity of nanocrystals, and the introduced materials can also be modified to integrate additional functions to further facilitate the absorption of nanocrystals. It is expected that the absorption ‘as a whole’ strategy of nanocrystals will provide different choices for the oral BCS IV drugs.

KEYWORDS:

• Nanocrystals
• oral BCS IV drug delivery
• pharmaceutical strategy
• surface modification
• absorption mechanism

Article highlights

• Instability and rapid dissolution are two major problems to be solved in oral BCS IV drug nanocrystals.

• Oral nanocrystals technology needs to change pharmaceutical strategy suitable for BCS IV drug.

• Rod-shaped nanocrystals have great advantages in oral absorption compared with other shapes of nanocrystals.

• The formulation of nanocrystals with multi-functional stabilizers (such as P-protein inhibitors) can stabilize nanocrystals and also improve oral absorption of nanocrystals.

• Surface modification is critical to maintaining the crystal structure of nanocrystals

• The ‘nanocages’ formed by cross-linking of stabilizers can ensure the stability of the nanocrystals not to be destroyed, and even provide a target for the connection of ligands.

• Liposomal nanocrystals can reduce the dissolution of BCS IV drug nanocrystals, helping nanocrystals to obtain efficient cell uptake.

• Adding nanocrystals to other systems is also an excellent strategy to improve the oral absorption of BCS IV drugs.

This box summarizes key points contained in the article.

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

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 Mega-project for Innovative Drugs (No. 2019ZX09721001), the National Natural Science Foundation of China (No. 81673378), the Project of Liaoning Provincial Department of Education (No. 2019LQN07), and the Liaoning Revitalization Talents Program (No. XLYC1908031).