Strategies to Obtain Encapsulation and Controlled Release of Small Hydrophilic Molecules.

Qi Li,Xiaosi Li,Chao Zhao

doi:10.3389/fbioe.2020.00437

Qi Li, Xiaosi Li + Show 1 more

Open Access

https://doi.org/10.3389/fbioe.2020.00437

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Abstract

The therapeutic effect of small hydrophilic molecules is limited by the rapid clearance from the systemic circulation or a local site of administration. The unsuitable pharmacokinetics and biodistribution can be improved by encapsulating them in drug delivery systems. However, the high-water solubility, very hydrophilic nature, and low molecular weight make it difficult to encapsulate small hydrophilic molecules in many drug delivery systems. In this mini-review, we highlight three strategies to efficiently encapsulate small hydrophilic molecules and achieve controlled release: physical encapsulation in micro/nanocapsules, physical adsorption via electronic interactions, and covalent conjugation. The principles, advantages, and disadvantages of each strategy are discussed. This review paper could be a guide for scientists, engineers, and medical doctors who want to improve the therapeutic efficacy of small hydrophilic drugs.

Highlights

Small hydrophilic molecules are widely used for treating diseases such as infectious diseases (Macielag, 2012; Zhang et al, 2015; Chandel et al, 2018), cancer (Xu et al, 2014; Zhao et al, 2016), and local anesthesia (Howell and Chauhan, 2009; Jug et al, 2010)
A larger internal volume leads to the higher efficiency of drug loading, while a stable liposome structure avoids the leakage of small molecular hydrophilic drugs
Ionized PEs in the solution can form a complex with oppositely charged PEs—a PE complex (PEC) (Meka et al, 2017). Such “chaotic” aggregation of polyanions and polycations might only be the result of partial mutual charge compensation, leaving a huge number of ionic sites compensated by small molecules with counter ions to preserve the electro neutrality (Philipp et al, 1989)

Summary

INTRODUCTION

Small hydrophilic molecules are widely used for treating diseases such as infectious diseases (Macielag, 2012; Zhang et al, 2015; Chandel et al, 2018), cancer (Xu et al, 2014; Zhao et al, 2016), and local anesthesia (Howell and Chauhan, 2009; Jug et al, 2010). Many delivery systems have been attempted and shown promise in encapsulation and sustained release of hydrophilic molecules (Vrignaud et al, 2011), most of them only work well for molecules with the moderate hydrophilicity and medium molecular weight When it comes to the super hydrophilic and very small molecules, their effectiveness is not adequate. Liposomes and polymersomes encapsulate small hydrophilic molecules inside the internal aqueous pockets to achieve a high encapsulation efficiency. A larger internal volume leads to the higher efficiency of drug loading, while a stable liposome structure avoids the leakage of small molecular hydrophilic drugs These essential parameters of liposomes can be adjusted to a great extent by the lipid membrane composition, chain length of the phospholipid, drug to lipid ratio, and charge property (Eloy et al, 2014). The clinical applications of polymersomes are hampered by the residual organic solvent, incompetent control of the early drug release, cumbersome fabrication steps, and toxicity concerns (Vrignaud et al, 2011; Anajafi and Mallik, 2015)

PHYSICAL ADSORPTION

Limitations

CONJUGATE DELIVERY SYSTEM

CONCLUSION AND PERSPECTIVES