Poly-arginines are strong tools to elevate the cellular uptake of nanopreparations. To learn the influence of poly-arginine (RRRRRRRR, R8) density on a series of properties of nanostructured lipid carrier (NLC), we build six R8 modified NLCs with different R8 densities (nR-NLC, where n represents the R8 ratio) by fusion–emulsion method with the aid of stearyl-R8. The pharmaceutical characteristics like size, zeta potential and in vitro drug release, cellular uptake, cytotoxicity to A549 cells and tissue distribution in S180 tumor-bearing mice of the six nR-NLCs are all investigated. It turns out that with as little as 2% weight ratio of stearyl-R8 modified on NLC, its pharmaceutical properties, especially zeta potential changes astonishingly; however, the stearyl-R8 ratio should be higher than 4% to upgrade the cellular uptake and cytotoxicity evidently; in the ex vivo tissue distribution assessment, the nR-NLC with less than 8% R8 showed similar tissue accumulation, while NLC with 10% R8 shows obvious acute toxicity to mice. Our study pays attention to the effect of the R8 ratio on the changes of cargo properties, and the results indicate that this topic is essential and worth to be further developed.

Polymeric micelles are widely used as suitable nano-carriers for a variety of therapeutic applications. Exploring the role of hydrophobic groups on the properties of the amphiphilic carrier and micelles were the aim of this study. Using hyaluronic acid (HA), cholesterol (CHOL) and octadecanoic acid (OA), two amphiphilic polymers were prepared and fully characterized by ¹H NMR, FTIR and DSC. Compared with HA–SA–CYS–OA, HA–SA–CYS–CHOL had a lower critical micellar concentration (CMC) producing docetaxel (DTX)-loaded micelles of a smaller particle size, higher encapsulation efficiency (EE) and drug loading (DL%). However, HA–SA–CYS–OA had the greater EE when loaded with coumarin-6 (Cou6), suggesting that hydrophobic groups had a degree of selectivity for drugs. Cellular uptake demonstrated that the two micelles clearly increased the internalization of DTX via CD44 receptor-mediated endocytosis. In vitro cytotoxic experiments showed that HA–SA–CYS–OA micelles were generally more cytotoxic to MCF-7, A549 and S-180 cells on account of the toxicity of octadecanoic acid while in vivo animal experiments confirmed that HA–SA–CYS–CHOL micelles exhibited better tumor-targeting properties and antitumor effects. From these preliminary evaluations, it is possible to conclude that hydrophobic groups not only affect the stability and drug-loading capacity of the amphiphilic carriers, but also influence the distribution, metabolism, excretion and ultimately, the antitumor efficacy of micelles.

Objective: For better treatment of circadian cardiovascular events, a novel Propranolol hydrochloride (PNH) delayed-release osmotic pump capsule was developed. Methods: The capsule body was designed of asymmetric membrane and the capsule cap was made impermeable. The physical characteristics of capsule body walls and membrane permeability were compared among different coating solutions. Results: The formulation with the glycerin and diethyl phthalate (DEP) ratio of 5:4 appeared to be the best. The lag time and subsequent drug release were investigated through assembling the capsule body with capsule caps of different length. WSR N-10 was chosen as the suspending for its moderate expanding capacity. The influence of factors (WSR N-10 content, NaCl content and capsule cap length) on the responses (lag time and drug release rate) was evaluated using central composite design-response surface methodology. A second-order polynomial equation was fitted to the data and actual response values were in good accordance with the predicted ones. The optimized formulation displayed complete drug delivery, zero-order release rate with 4-h lag time. The results of in vivo pharmacokinetics in beagle dogs clearly suggested the controlled and sustained release of PNH from the system and that the relative bioavailability of this preparation was about 1.023 comparing the marketed preparation. Conclusions: These results indicate that by the adjustment of capsule cap length, PNH could be developed as a novel pulsatile and controlled drug delivery system.