Some kinds of amphiphilic lipids can spontaneously self-assemble with a proper ratio of water to form liquid crystalline, also known as cubic phase. With a curved bi-continuous lipid bilayer and two congruent networks of water channels, cubic phases can enclose hydrophilic, amphiphilic and hydrophobic drugs for delivery. Nanostructured cubosomes, prepared by fragmentation of bulk cubic phase gels or lyotropic methods, retain the same inner structure of cubic phase and possess much larger specific surface area and lower viscosity. These unique properties make cubosomes excellent delivery systems applicable for oral, mucosal, transdermal and parenteral drug delivery. This article gave an overview of the accelerated development and current status of cubosomes research, with respect to their preparation, characteristics and applications in pharmaceutics.

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The objective of this study was to develop a novel anhydrous reverse micelle nanoparticles (ARM-NPs) system to overcome the sedimentation instability of peptide-containing pressurized metered-dose inhalers (pMDIs). A bottom-up method was utilized to fabricate ARM-NPs. Tertiary butyl alcohol (TBA)/water system, freeze-drying and lipid inversion method were successively used to produce the ARM-NPs for pMDI. Various characteristics of ARM-NPs were investigated including particle size, morphology, secondary structure of the peptide drug, aerosolization properties and storage stability. As revealed by the results, ARM-NPs with spherical shape possessed 147.7 ± 2.0 nm of particle size with 0.152 ± 0.021 PdI. The ARM-NPs for pMDI had satisfactory fine particle fraction (FPF) value of 46.99 ± 1.33%, while the secondary structure of the peptide drug was unchanged. Stability tests showed no pronounced sedimentation instability for over 12 weeks at 4-6 °C. Furthermore, a hypothesis was raised to explain the formation mechanism of ARM-NPs, which was verified by the differential scanning calorimetry analysis. The lecithin employed in the reverse micelle vesicles could serve as a steric barrier between peptide drugs and bulk propellant, which prevented the instability of peptide drugs in hydrophobic environment. Homogenous particle size could avoid Ostwald ripening phenomenon of particles in pMDIs. It was concluded that the ARM-NPs for pMDI could successfully overcome sedimentation instability by the steric barrier effect and homogeneous particle size.

Nanoparticles (NPs) have shown potential in cancer therapy, while a single administration conferring a satisfactory outcome is still unavailable. To address this issue, the dissolving microneedles (DMNs) were developed to locally deliver functionalized NPs with combined chemotherapy and photothermal therapy (PTT). α -Tocopheryl polyethylene glycol succinate (TPGS)/hyaluronic acid (HA) dual-functionalized PLGA NPs (HD10 NPs) were fabricated to co-load paclitaxel and indocyanine green. HD10 NPs significantly enhanced the cytotoxicity of low-dose paclitaxel because of active and mitochondrial targeting by HA and TPGS, respectively. PTT could further sensitize tumor cells toward chemotherapy by promoting apoptosis into the advanced period, highly activating caspase 3 enzyme, and significantly reducing the expression of survivin and MMP-9 proteins. Further, the anti-tumor effects of HD10 NPs delivered through different administration routes were conducted on the 4T1 tumor-bearing mice. After a single administration, HD10 NPs delivered with DMNs showed the best anti-tumor effect when giving chemotherapy alone. As expected, the anti-tumor effect was profoundly enhanced after combined therapy, and complete tumor ablation was achieved in the mice treated with DMNs and intra-tumor injection. Moreover, DMNs showed better safety due to moderate hyperthermia. Therefore, the DMNs along with combined chemo-photothermal therapy provide a viable treatment option for superficial tumors.

The poly (lactic‐co‐glycolic acid) nanoparticle (PLGA NP) has been widely used in the biomedical field. However, it is insensitive to degradation upon laser irradiation, resulting in a limited increase in drug release, which compromises the therapeutic efficacy. To actively promote drug release, the biphasic α‐tocopheryl succinate (TPGS) functionalized PLGA NPs (PTNPs) are developed by introducing TPGS into the aqueous and organic phase to generate pores in the PLGA core during preparation. Paclitaxel and indocyanine green are encapsulated in the PTNPs to realize chemo‐photothermal combined therapy, and PTNPs are delivered through dissolving microneedles (DMNs) for local treatment in melanoma. PTNPs show enhanced drug release and improved cytotoxicity due to their greater ability in inhibiting cell microtubule depolymerization. In vivo tumor suppression investigation and ki‐67 immunohistochemical staining of tumor tissue further show the superiority of PTNPs loaded DMNs against tumor growth, and photothermal therapy synergistically enhances the chemotherapeutic effect of PTNPs. Moreover, the living imaging of mice demonstrates that the drug is successfully retained in the tumor tissue to avoid it entering into the circulation and producing adverse effects. Therefore, the PTNPs loaded DMNs show a favorable prospect in the treatment of superficial tumor.