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.

A two-step organic sol–gel process for the preparation of monodispersed or narrow-dispersed melamine–formaldehyde (MF) resin polymer colloidal spheres in water was developed. A modified Stöber process was used to coat the MF colloidal spheres with silica shells, which rendered the surfaces of these colloidal spheres easily modifiable. The prepared MF@silica core–shell composite colloidal spheres were then bioconjugated with bovine serum albumin to demonstrate the feasibility of using these colloidal particles as supporting materials in bioassays. The particle formation mechanism of this organic sol–gel process was investigated by time-resolved microscopic analysis. The prepared MF nano-/microscale resin polymer spheres were monodispersed or narrow-dispersed with a controllable average size ranging from 30 nm to 250 nm and from 0.8 μm to 4.5 μm. The spheres were stable in aqueous or organic solvents and after heat treatment above 300 °C. A “controlled aggregation” model was proposed to explain the influences of the key factors in this process.