《Table 5–Summary of the differences,advantages,and disadvantages of different type nanosystems of UA

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《Evolution from small molecule to nano-drug delivery systems:An emerging approach for cancer therapy of ursolic acid》

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The following several aspects should be considered in promoting UA nanomedicines from preclinical levels to the clinical settings:（i） The implementation of US Food and Drug Administration（FDA)-approved materials as nanocarriers of UA can consequently expedite its clinical transformation.（ii）To address the issues of short blood circulation halflife and nonspecific protein adsorption，the surface of UA nanoparticles can be modified by various materials，such as PEG or polysorbate 80，dysopsonins proteins（e.g.，clusterin and albumin），and self-markers （e.g.，CD47 peptides）and membrane of erythrocytes，leukocytes，cancer cells or thrombocytes[36，119].(iii） Additionally，the physicochemical characterization of UA nanoparticles should be carried out under similar clinical conditions.（iv） Moreover，the rational design of nanosystems is important to develop UA nanosystems with high loading capacity，which will further affect its dosage and therapeutic efficacy in clinical treatment[124].Therefore，the development of nanosystems with active targeting-ligands or stimuli-responsive properties is valuable for improving the targetability and therapeutic efficacy of conventional UA nanosystems.More comprehensive preclinical and clinical trials should be conducted to further validate its therapeutic efficacy.It is also noteworthy that the combination of UA with other therapeutic agents could result in synergistic effects and offer a better therapeutic index.On the other hand，the novel composite nanosystems with two or more anticancer agents will help to reduce adverse effects by reducing the single dosage of chemotherapeutic agent.In addition to these considerations，manufacturing UA nanosystems at an industrial level should consider the cost-benefit and follow GLP and GMP （good laboratory and manufacturing practice）.