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• Novel self-assembled carrier-free SN38/Ce6 NPs were fabricated. • The driving forces for the self-assembly process were exhaustively disclosed. • The NPs exhibited higher in vitro/in vivo 1O 2 generation capacity. • The NPs displayed enhanced cellular uptake efficiency and tumor accumulation. • The NPs showed superior in vivo antitumor efficacy and minimal systemic toxicity. The combination therapy strategy based on both chemotherapy and photodynamic therapy (PDT) exhibits great potential for advanced cancer treatment. Multimodal nanodrug delivery systems based on both chemotherapeutic drug and photodynamic agent have been proven to possess excellent synergistic efficacy. In this study, 7-ethyl-10-hydroxycamptothecin (SN38) and chlorin e6 (Ce6) were co-assembled into novel carrier-free nanoparticles (SN38/Ce6 NPs) via simple antisolvent precipitation method. As expected, SN38/Ce6 NPs exhibited uniform morphology with a particle size of around 150 nm and a zeta potential of about −30 mV, good stability in aqueous solution/at lyophilized state and high cellular uptake efficiency against murine mammary carcinoma (4T1) cell lines. Besides, enhanced singlet oxygen generation capacity of the nanoparticles was both observed in test-tube and in 4T1 cell lines in contrast with Ce6 injection. Moreover, a ∼85 % inhibition rate of SN38/Ce6 NPs with laser was detected, which was significantly higher (P < 0.05) than those without laser (∼65 %) and injections (less than 20 %), verified the excellent synergistic antitumor efficacy of the nanoparticles due to combined chemo-photodynamic therapy, enhanced tumor accumulation and higher cellular internalization. Notably, chemical thermodynamic method and molecular dynamics (MD) simulations supplied solid data and visual images to estimate the driving forces for the self-assembly process of the carrier-free nanoparticles as primary hydrophobic interactions (π-π stacking) and subordinate hydrogen bonds. Conclusively, the above self-assembled carrier-free nanoparticles represented a promising synergistic anticancer strategy capable of maximal therapeutic efficacy and minimal systemic toxicity. Moreover, the application of thermodynamic method together with MD simulations in the investigation of NPs self-assembly process also provided new ideas for the assembly mechanism exploration of more complicated nanodrug delivery system. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • HPMCAS-HF exhibited superior recrystallization inhibition property for nimodipine. • Nimodipine solid dispersion was prepared with HPMCAS-HF by hot-melt extrusion. • NM-SD tablets were compressed with nimodipine solid dispersion. • NM-SD tablets exhibited higher solubility and enhanced dissolution profiles. • Hot-melt extrusion technique could be employed to improve bioavailability of nimodipine formulations. Abstract In current study, a novel nimodipine solid dispersion (NM-SD) was prepared by hot-melt extrusion (HME) with Hypromellose methylcellulose acetate succinate (H type and fine grades, HPMCAS-HF) for its excellent recrystallization inhibition effects. NM was confirmed to exist as an amorphous state in NM-SD by differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), hot stage microscopy (HSM) and scanning electron micrographs (SEM). FT-IR analysis illustrated hydrogen bond interaction between drugs and excipients in NM-SD. The release behavior of NM-SD tablets was investigated in the dissolution medium of pH 6.8 for the in vitro study, which showed that the release of nimodipine could be realized in vitro without recrystallization within two hours. The in vivo pharmacokinetic profiles study in Sprague-Dawley rats was also determined. It was obvious that the C max value of NM-SD tablets made by dry granulation was slightly higher than Nimotop®, while the area under the curve, AUC (0-t) exhibited no significant difference between them. In conclusion, the solubility of NM and dissolution rate of NM-SD tablets were greatly improved by HME due to the recrystallization inhibition characteristic of HPMCAS-HF. [ABSTRACT FROM AUTHOR]

• Novel Lip-PTX/BSA NPs were fabricated via modified thin-film method. • The fabrication process avoided direct contact of BSA with toxic organic solvents. • The fabrication process eliminated organic solvent residual. • The NPs exhibited excellent colloidal stability and sustained release manner. • The NPs showed effective in vitro/vivo antitumor efficacy. Organic solvents have been reported to exert certain influence on the structure and drug loading efficiency of albumin. It is urgent to develop organic solvent-free albumin-based paclitaxel nanoparticles for effective anticancer therapy. In this study, novel PTX liposome-albumin composite nanoparticles (Lip-PTX/BSA NPs) aimed at avoiding the direct contact of albumin with toxic organic solvents and enhancing the colloidal stability of the formulation were prepared. To methodically evaluate the impacts of multifarious factors on the critical characteristics of the nanoparticles, Box-Behnken design was applied in the formulation optimized process. Ratio of drug-phosphatidylcholine (EPC), ratio of drug-BSA and pH of the media were chosen as the independent variables, while particle size and drug-loading content (DLC) loss rate were applied as the selected response variables. A quadratic model fitted best to describe the data with maximal lack-of-fit p-value and minimum sequential p-value. Three-dimension surface figures were utilized to describe the correlation of independent variables with response variables. Optimized formulation of the nanoparticles with size of 116.2 ± 2.0 nm and zeta potential of -18.4 ± 1.01 mV were obtained with a high encapsulation efficiency of 99.8%. PTX was involved physical interaction with the excipient during the preparation process of the nanoparticles. The release of PTX from Lip-PTX/BSA NPs exhibited a sustained release manner compared to albumin-bound PTX (nab-PTX) and Taxol. Besides, Lip-PTX/BSA NPs presented enhanced in vitro cytotoxicity against 4T1 cells due to highly nonspecific internalization in the cytoplasm. Simultaneously, Lip-PTX/BSA NPs showed effective in vivo antitumor efficacy against 4T1 bearing BALB/c mice, while no apparent adverse effect was observed by histological section and blood biochemical analysis. In conclusion, the novel Lip-PTX/BSA NPs could be applied as a promising drug delivery system for PTX to exert efficient cancer curative effects in clinic. [ABSTRACT FROM AUTHOR]