Gambogic acid (GA), a kind of dry resin secreted by the Garcinia hanburyi tree, is a natural active ingredient with various biological activities, such as anti-cancer, anti-inflammatory, antioxidant, anti-bacterial effects, etc. An increasing amount of evidence indicates that GA has obvious anti-cancer effects via various molecular mechanisms, including the induction of apoptosis, autophagy, cell cycle arrest and the inhibition of invasion, metastasis, angiogenesis. In order to improve the efficacy in cancer treatment, nanometer drug delivery systems have been employed to load GA and form micelles, nanoparticles, nanofibers, and so on. In this review, we aim to offer a summary of chemical structure and properties, anti-cancer activities, drug delivery systems and combination therapy of GA, which might provide a reference to promote the development and clinical application of GA.

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Purpose Nose-to-brain drug delivery is an effective approach for poorly soluble drugs to bypass the blood–brain barrier. A new drug intranasal delivery system, a nanosuspension-based in situ gel, was developed and evaluated to improve the solubility and bioavailability of the drug and to prolong its retention time in the nasal cavity. Materials and Methods Breviscapine (BRE) was chosen as the model drug. BRE nanosuspensions (BRE-NS) were converted into BRE nanosuspension powders (BRE-NP). A BRE nanosuspension in situ gelling system (BRE-NG) was prepared by mixing BRE-NP and 0.5% gellan gum (m/v). First, the BRE-NP were evaluated in terms of particle size and by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Subsequently, the critical ionic concentration of the gellan gum phase transition, influence of the deacetylated gellan gum (DGG) concentration on the expansion coefficient (S%), water-holding capacity, rheological properties and in vitro release behaviour of the BRE-NG were investigated. The pharmacokinetics and brain distribution of the BRE-NG after intranasal administration were compared with those of the intravenously injected BRE-NP nanosuspensions in rats. Results The rheology results demonstrated that BRE-NG was a non-Newtonian fluid with good spreadability and bioadhesion performance. Moreover, the absolute bioavailability estimated for BRE-NG after intranasal administration was 57.12%. The drug targeting efficiency (DTE%) of BRE in the cerebrum, cerebellum and olfactory bulb was 4006, 999 and 3290, respectively. The nose-to-brain direct transport percentage (DTP%) of the cerebrum, cerebellum and olfactory bulb was 0.975, 0.950 and 0.970, respectively. Conclusion It was concluded that the in situ gel significantly increased the drug retention time at the administration site. Therefore, the nanosuspension-based in situ gel could be a convenient and effective intranasal formulation for the administration of BRE.

Pulmonary inhalation administration is an ideal approach to locally treat lung disease and to achieve systemic administration for other diseases. However, the complex nature of the structural characteristics of the lungs often results in the difficulty in the development of lung inhalation preparations. Nanocrystals technology provides a potential formulation strategy for the pulmonary delivery of poorly soluble drugs, owing to the decreased particle size of drug, which is a potential approach to overcome the physiological barrier existing in the lungs and significantly increased bioavailability of drugs. The pulmonary inhalation administration has attracted considerable attentions in recent years. This review discusses the barriers for pulmonary drug delivery and the recent advance of the nanocrystals in pulmonary inhalation delivery. The presence of nanocrystals opens up new prospects for the development of novel pulmonary delivery system. The particle size control, physical instability, potential cytotoxicity, and clearance mechanism of inhaled nanocrystals based formulations are the major considerations in formulation development.

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