[Research progress on liposome and nanomicelle targeted drug delivery system across blood-brain barrier].

The blood-brain barrier(BBB), a protective barrier between brain tissues and brain capillaries, can prevent drugs from entering the brain tissues to exert the effect, which greatly increases the difficulty in treating brain diseases. The drug delivery system across the BBB can allow efficient drug delivery across the BBB by virtue of carriers and formulations, thereby enhancing the therapeutic effect of drugs on brain tissue diseases. Liposomes and micelles have been extensively studied with advances in the targeted therapy across the BBB for the brain due to their unique structures and drug delivery advantages. This study summarized the research status of liposome and micelle drug delivery systems across the BBB based on the literature in recent years and analyzed their application advantages and mechanism in terms of trans-BBB capability, targeting, and safety. Moreover, the problems and possible countermeasures in the research on trans-BBB liposomes and micelles were discussed according to the current clinical translation, which may provide refe-rences and ideas for the development of trans-BBB targeted nano-drugs.

Enteric polymer based on pH-responsive aliphatic polycarbonate functionalized with vitamin E to facilitate oral delivery of tacrolimus.

To improve the bioavailability of orally administered drugs, we synthesized a pH-sensitive polymer (poly(ethylene glycol)-poly(2-methyl-2-carboxyl-propylene carbonate)-vitamin E, mPEG-PCC-VE) attempting to integrate the advantages of enteric coating and P-glycoprotein (P-gp) inhibition. The aliphatic polycarbonate chain was functionalized with carboxyl groups and vitamin E via postpolymerization modification. Optimized by comparison and central composite design, mPEG113-PCC32-VE4 exhibited low critical micelle concentration of 1.7 × 10(-6) mg/mL and high drug loading ability for tacrolimus (21.2% ± 2.7%, w/w). The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. Less than 4.0% tacrolimus was released under simulated gastric fluid after 2.5 h, whereas an immediate release was observed under simulated intestinal fluid. The mPEG113-PCC32-VE4 micelles significantly increased the absorption of P-gp substrate tacrolimus in the whole intestine. The oral bioavailability of tacrolimus micelles was 6-fold higher than that of tacrolimus solution in rats. This enteric polymer therefore has the potential to become a useful nanoscale carrier for oral delivery of drugs.

Dissolution and oral bioavailability enhancement of praziquantel by solid dispersions.

The aim of the present investigation was to enhance the solubility, dissolution, and oral bioavailability of praziquantel (PZQ), a poorly water-soluble BCS II drug (Biopharmaceutical Classification System), using a solid dispersion (SD) technique involving hydrophilic copolymers. The SD formulations were prepared by a solvent evaporation method with PZQ and PEG 4000 (polyethylene glycol 4000), PEG 6000, or P 188 polymers at various weight ratios or a combination of PEG 4000/P 188. The optimized SD formulation, which had the highest solubility in distilled water, was further characterized by its surface morphology, crystallinity, and dissolution in 0.1 M HCl with 0.2% w/v of sodium dodecyl sulfate (SDS). X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR) revealed the amorphous form of PZQ in the SDs. Moreover, at an oral dosage of 5 mg/kg PZQ, the SDs had higher Cmax values and areas under the curve (AUCs) compared to those of commercial PZQ tablets. Preparation of PZQ-loaded SDs using PEG 4000/P 188 is a promising strategy to improve the oral bioavailability of PZQ.

Star-shape redox-responsive PEG-sheddable copolymer of disulfide-linked polyethylene glycol-lysine-di-tocopherol succinate for tumor-triggering intracellular doxorubicin rapid release: head-to-head comparison.

A redox-responsive poly(ethylene glycol) (PEG)-sheddable copolymer of disulfide-linked PEG 5000-lysine-di-tocopherol succinate (P(5k)SSLV) is developed which can self-assemble into nanomicelles in aqueous condition and trigger the rapid release of encapsulated drugs within tumor cells. The reduction-insensitive doxorubicin (DOX)-loaded P(5k)LV (P(5k)LV-DOX) nanomicelles are further prepared. Then head-to-head comparison of P(5k)SSLV-DOX, P(5k)LV-DOX and DOX-Sol is performed concerning in vitro release, cytotoxicity, cellular uptake and apoptosis. Results show that P(5k)SSLV-DOX nanomicelles have a faster DOX release, a higher anti-tumor activity and more DOX concentrating in the nucleus than P(5k)LV-DOX nanomicelles. In conclusion, the redox-responsive P(5k)SSLV nanomicelles might hold a great potential to improve chemotherapy by tumor-triggering intracellular rapid release. The outcomes of this study also address the significance of such head-to-head comparison studies in translational research of nanomedicine.