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Novel transdermal cataplasms have been designed to improve permeability of poorly soluble drugs by different pretreatments. Nanocrystal and porous silica solid dispersions were loaded with Tanshinone IIA and incorporated into a cross-linked hydrogel matrix of cataplasm. It was shown that the small particle size and improved dissolution would increase dermal bioavailability. The adhesion, rheological properties, drug release, skin permeation, skin deposition and in vivo skin absorption of the different formulations were investigated. In an in vitro experiment using mouse skin, cumulative amount of drug permeated within 24 h was 7.32 ± 0.98 μg/cm2 from conventional cataplasm, 13.14 ± 0.70 μg/cm2 from nanocrystal-loaded cataplasm and 11.40 ± 0.13 μg/cm2 from porous silica solid dispersion-loaded cataplasm. In vitro dissolution profiles showed that drug release was 76.5% and 74.9% from two optimized cataplasms within 24 h, while conventional cataplasm was 55.0%. The cross-linking characteristics of the cataplasms were preserved after incorporation of different drug forms, while the elastic and viscous behaviors of the hydrogel layers increased. In vivo evaluation by CLSM showed the more favorable skin permeation for two optimized cataplasms. These findings suggest that applications of nanocrystal and porous silica systems on cataplasms enable effective transdermal delivery of poorly soluble drugs. The resulting drug delivery and rheological properties are desirable for transdermal application.AbbreviationAll the abbreviations that appear in this article are shown in Table 1.

Aim: The aim of this study was to improve solubility and antitumour ability in vitro of tetrandrine (Tet) via preparing nanosuspensions (NSs).Methods: The Tet-NSs were prepared by wet media milling...

This study aims to develop nanosuspensions for improving the dissolution of poorly water-soluble cyclovirobuxine D (CVB-D) containing a binary stabilizer system and further characterize the stabilization potential and physical–chemical variables of CVB-D nanosuspensions. Binary stabilizers of croscarmellose sodium (CCS) with hydroxypropyl methyl cellulose acetate succinate (HPMCAS), hydroxypropyl β cyclodextrin (H-β-CD) and cross-linked polyvinylpyrrolidone (CP) were chosen for nanosuspensions. The rapid dissolution of CVB-D nanosuspensions was achieved by wet media milling. By observing the stability after 30 days of storage, the combination of CCS with HPMCAS was determined to be the most effective binary system. The relative order of effectiveness of the combinations was as follows: CCS/HPMCAS > CCS/CP > CCS/H-β-CD. The obtained particle size and polydispersity index were both within an acceptable range. The particle surface morphology, miscibility, thermal stability and molecular binding energy of CVB-D nanosuspensions were subsequently characterized by SEM, FTIR, TG-DSC and NMR spectroscopy. The results revealed that smaller particle size and better miscibility have a significant contribution to the dissolution and stability of CVB-D nanosuspensions. Overall, these promising results open new perspectives for improving the stability and dissolution rate for CVB-D and other alkaloids.

Objectives: Stability issues are inevitable problems that are encountered in nanosuspension (NS) technology developments and in the industrial application of pharmaceuticals. This study aims to assess the stability of wet-milled cepharanthine NSs and elucidate the stabilization mechanisms of different stabilizers. Methods: The aggregation state was examined via scanning electron microscopy, laser diffraction, and rheometry. The zeta potential, stabilizer adsorption, surface tension, and drug-stabilizer interactions were employed to elucidate the stabilization mechanisms. Results: The results suggest that croscarmellose sodium (CCS), D-α-tocopherol polyethylene glycol 1000 succinate (TPGS), or polyvinyl pyrrolidone VA64 (PVP VA64) alone was able to prevent nanoparticle aggregation for at least 30 days. Attempts to evaluate the stability mechanisms of different stabilization systems revealed that CCS improved the steric-kinetic stabilization of the NSs, attributed to its high viscosity, swelling capacity, and physical barrier effects. In contrast, the excellent physical stability of TPGS systems was mainly due to the reduced surface tension and higher crystallinity. PVP VA64 can adsorb onto the surfaces of nanoparticles and stabilize the NS via steric forces. Conclusion: This study demonstrated the complex effects of CCS, TPGS, and PVP VA64 on cepharanthine NS stability and presented an approach for the rational design of stable NSs.

Objectives Multidrug resistance (MDR) remains a primary challenge in breast cancer treatment. In the present study, D-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS)-coated docetaxel-loaded liposomes were developed as a novel drug delivery system to reverse MDR and enhance breast cancer therapy compared with the traditional liposomes, DSPE-mPEG-coated liposomes (stealth liposomes) and commercial Taxotere®. Key findings Liposomes were prepared by thin – film dispersion method. Evaluations were performed using human breast cancer MCF-7 and resistant MCF-7/ADR cells. The reversal multidrug-resistant effect was assessed by P-gp inhibition assay, cytotoxicity, cellular uptake and apoptosis assay. Results The TPGS-chol-liposomes were of an appropriate particle size (140.0 ± 6.0 nm), zeta potential (−0.196 ± 0.08 mv), high encapsulation efficiency (99.0 ± 0.9) and favourable in vitro sustained release. The TPGS-coated liposomes significantly improved cytotoxicity and increased the intracellular accumulation of docetaxel in both types of breast cancer cells. The TPGS-coated liposomes were confirmed to induce apoptosis via a synergistic effect between docetaxel and TPGS. It was demonstrated that TPGS enhanced the intracellular accumulation of drug by inhibiting overexpressed P-glycoprotein. Conclusions The TPGS-conjugated liposomes showed significant advantages in vitro compared with the PEG-conjugated liposomes. The TPGS-conjugated liposomes could reverse the MDR and enhance breast cancer therapy.

Cilnidipine (CLD) is extensively used in the treatment of hypertension; however, it has extremely low solubility which limits its clinical application. The purpose of the present research was to improve the dissolution rate and oral bioavailability of CLD by preparing a nanosuspension. The CLD nanosuspension (CLD-NS) was developed using a wet-milling method with PVP VA64 as the steric stabilizer and SLS as the electrostatic stabilizer. The formulated CLD-NS displayed a narrow and uniform particle size distribution with a mean particle size of 312 nm, and a marked increase in the dissolution of CLD-NS in different dissolution media was observed compared with bulk CLD. The crystallinity of the drug and molecular interactions between drug and stabilizers were investigated by differential scanning calorimetry (DSC), X-ray powder diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), and Raman spectroscopy, respectively. Furthermore, the in vivo pharmacokinetics of the formulated CLD-NS were evaluated in Sprague-Dawley rats by high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS). The results indicated that the Cmax and AUC0-24 of CLD-NS were 3.13-fold and 2.38-fold higher than those of bulk CLD, respectively. Moreover, the Cmax and AUC0-24 of CLD-NS were increased 1.65-fold and 2.17-fold, compared with commercial CLD capsules. These results indicated the significant increase in CLD bioavailability.