High drug-loading nanomedicines: progress, current status, and prospects

Abstract

Drug molecules transformed into nanoparticles or endowed with nanostructures with or without the aid of carrier materials are referred to as "nanomedicines" and can overcome some inherent drawbacks of free drugs, such as poor water solubility, high drug dosage, and short drug half-life in vivo. However, most of the existing nanomedicines possess the drawback of low drug-loading (generally less than 10%) associated with more carrier materials. For intravenous administration, the extensive use of carrier materials might cause systemic toxicity and impose an extra burden of degradation, metabolism, and excretion of the materials for patients. Therefore, on the premise of guaranteeing therapeutic effect and function, reducing or avoiding the use of carrier materials is a promising alternative approach to solve these problems. Recently, high drug-loading nanomedicines, which have a drug-loading content higher than 10%, are attracting increasing interest. According to the fabrication strategies of nanomedicines, high drug-loading nanomedicines are divided into four main classes: nanomedicines with inert porous material as carrier, nanomedicines with drug as part of carrier, carrier-free nanomedicines, and nanomedicines following niche and complex strategies. To date, most of the existing high drug-loading nanomedicines belong to the first class, and few research studies have focused on other classes. In this review, we investigate the research status of high drug-loading nanomedicines and discuss the features of their fabrication strategies and optimum proposal in detail. We also point out deficiencies and developing direction of high drug-loading nanomedicines. We envision that high drug-loading nanomedicines will occupy an important position in the field of drug-delivery systems, and hope that novel perspectives will be proposed for the development of high drug-loading nanomedicines.

Keywords: fabrication strategy; high drug loading; nanocarriers; nanomedicines; optimum proposal.

Figure 1

Preparation and temperature-dependent working mechanism of the cationic, thermosensitive, copolymer-capped MSNPs. Abbreviations: MSNPs, mesoporous silica nanoparticles; NIPAAm, N-isopropylacrylamide; BVIm, butyl vinylimidazolium.

Figure 2

Synthesis, drug loading, and surface modification of MCNPs. Abbreviations: MCNPs, mesoporous carbon nanoparticles; DSPE, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine; mPEG, methoxy polyethylene glycol; oMCNs, oxidized mesoporous carbon nanospheres; Dox, doxorubicin; PEG, polyethylene glycol.

Figure 3

Dox encapsulation in HMCNCs and pH-stimulated release of Dox from folate–HMCNC-Dox. Abbreviations: Dox, doxorubicin; HMCNC, hollow magnetic colloidal nanocrystal; PAA, polyacrylic acid.

Figure 4

Formation of absorption/desorption-type MOF-based nanomedicine and MBioF-type nanomedicine by coordination-directed self-assembly processes. Abbreviations: MOF, metal–organic framework; MBioF, metal–biomolecule framework.

Figure 5

Amphiphilic CPT–polymer conjugates (OEG-CPT and OEG-DiCPT) and their self-assembly into nanocapsules to load other hydrophilic drug. Note: OEG-DiCPT means two CPT molecules were conjugated to one OEG molecule. Abbreviations: CPT, camptothecin; OEG, oligoethylene glycol.

Figure 6

Formation of mPEG-b-Dox micelles. Abbreviations: mPEG, methoxy polyethylene glycol; Dox, doxorubicin.

Figure 7

Formation of ICP I-type nanomedicine and ICP II-type nanomedicine and their pH-responsive release. Abbreviation: ICP, infinite coordination polymer.

Figure 8

Preparation and functionalization of MDNCs. Abbreviations: MDNC, multidrug nanocrystal; PEG, polyethylene glycol; PMH, polymaleic anhydride-alt-1-octadecene.

Figure 9

Ir-Cb ADDC following natural method (A) and CPT-FUDR ADDCs following modified method (B). Abbreviations: Ir, irinotecan; Cb, chlorambucil; ADDCs, amphiphilic drug–drug conjugates; CPT, camptothecin; FUDR, fluorodeoxyuridine; DCC, dicyclohexylcarbodiimide; DMAP, dimethylaminopyridine; RT, room temperature; DMSO, dimethyl sulfoxide.

Figure 10

Synthesis and functionalization of Tb(III)-DSCP ICPs. Notes: Reprinted (in part) with permission from Rieter WJ, Pott KM, Taylor KM, Lin WB. Nanoscale coordination polymers for platinum-based anticancer drug delivery. Journal of the American Chemical Society. 2008;130(35):11584–11585. Copyright © 2008 American Chemical Society. Abbreviations: DSCP, disuccinatocisplatin; ICPs, infinite coordination polymers; NCP, nano-coordination polymer; PVP, polyvinylpyrrolidone; TEOS, tetraethyl orthosilicate.

Scheme 1

Fabrication strategies of high drug-loading nanomedicines. Abbreviations: MSNPs, mesoporous silica nanoparticles; MCNPs, mesoporous carbon nanoparticles; MMCNCs, mesoporous magnetic colloidal nanocrystal clusters; MOFs, metal–organic frameworks; LPDCs, linear polymer–drug conjugates; BPDCs, branched PDCs; ICP, infinite coordination polymer; DNCs, drug nanocrystals; ADDCs, amphiphilic drug–drug conjugates; MBioFs, metal–biomolecule frameworks.