Synthesis and characterization of amphiphilic star-shaped copolymers based on ß-cyclodextrin for micelles drug delivery.

PURPOSE: A series of ß-CD amphiphilic star-shaped copolymers with exceptional characteristics were synthesized and their potential as carriers for micelles drug delivery was investigated. METHODS: A series of amphiphilic copolymers based on ß-CD were synthesized by introducing poly (acrylic acid)-co-poly(methyl methacrylate)-poly (vinyl pyrrolidone) or poly (acrylic acid)-co-poly(methyl methacrylate)-co-poly(monoacylated-ß-CD)-poly (vinyl pyrrolidone) blocks to the primary hydroxyl group positions of ß-CD. The micellization behavior of the copolymers, the synthesis conditions, characteristics, drug release in vitro and tissue distribution of vinpocetine (VP) micelles in vivo were investigated. RESULTS: Around 60 types of ß-CD amphiphilic star-shaped copolymers were successfully synthesized and the critical micelle concentration ranged from 9.80 × 10-4 to 5.24 × 10-2g/L. The particle size, drug loading and entrapment efficiency of VP-loaded ß-CD-P4 micelles prepared with optimal formulation were about 65 nm, 21.44 ± 0.14%, and 49.05 ± 0.36%, respectively. The particles had good sphericity. The cumulative release rates at 72 h of VP-loaded ß-CD-P4 micelles in pH 1.0, pH 4.5, pH 6.5, or pH 7.4 media were 93%, 69%, 49%, and 43%, respectively. And, the lung targeting efficiency of VP-loaded ß-CD-P4 micelles was 8.98 times higher than that of VP injection. CONCLUSION: The VP-loaded ß-CD-P4 micelles exhibited controlled-release property, pH-induced feature and lung targeting capacity compared with VP injection, suggesting that the ß-CD-P4 copolymers are an excellent candidate for micelles drug delivery.

Preparation and application of subdivided tablets using 3D printing for precise hospital dispensing.

This study aimed to use three-dimensional printing technology to provide patients with accurate, safe and convenient subdivided drugs and bring the transformation of subdivided drugs' fabrication in the hospital. The formulation, preparation process, model and printing parameters, relationship between dose and preset model for printing of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg subdivided tablets prepared by three-dimensional printers were investigated in the study. The three-dimensional printed material consists of commercial tablets powders and other excipients, including lactose, corn starch, microcrystalline cellulose, and so on. Mass variation, drug content and drug content uniformity of subdivided tablets obtained by three-dimensional printing were compared with the pharmacists splitting subdivided tablets. Besides, the results from fourier transform infrared spectroscopy, differential scanning calorimetry and X-ray powder diffraction confirmed that the preparation process of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg did not change the crystal structure of the active pharmaceutical ingredient. Furthermore, mass variation, drug content range and drug content uniformity of spironolactone of 2 mg, 4 mg and hydrochlorothiazide of 5 mg tablets split by pharmacists failed to comply with European Pharmacopoeia and Chinese Pharmacopoeia, while those of the three-dimensional printed subdivided tablets did. After the review of the ethics committee as a new technology for hospital dispensing, three-dimensional printed spironolactone subdivided tablets of 2 mg have been used in clinical inpatients and was accepted by pharmacists, nurses and patients. Compared with tablets subdivided split by pharmacists, three-dimensional printed spironolactone tablets of 2 mg were more accurate, safer and more customized, which indicated considerable potential in using three-dimensional printing technology as a new method for hospital dispensing.

mPEG-PLA/TPGS mixed micelles via intranasal administration improved the bioavailability of lamotrigine in the hippocampus.

PURPOSE: This study aimed to develop a novel methoxy poly(ethylene glycol)-poly(lactide) (mPEG-PLA)/D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) mixed micelle drug delivery system to improve lamotrigine (LTG) distribution in the hippocampus. METHODS: LTG-loaded mPEG-PLA/TPGS mixed micelles and LTG-loaded mPEG-PLA micelles were formulated, and their characteristics, particle size, surface morphology, and release behavior in vitro were researched. Then, a microdialysis sampling technique coupled with two validated chromatographic systems was developed for the continuous measurement of the protein-unbound form of LTG in the rat plasma and hippocampus after administering two kinds of micelles and LTG solution intranasally. RESULTS: The drug loading and mean size of LTG-loaded micelles and LTG-loaded mixed micelles prepared with optimal formulation were 36.44%±0.14%, 39.28%±0.26%, 122.9, and 183.5 nm, respectively, with a core-shell structure. The cumulative release rate in vivo of LTG-loaded mixed micelles was 84.21% at 24 hours and showed more sustained release while that of LTG-loaded micelles was 80.61% at 6 hours. The Tmax and area under concentration-time curve from zero to time of last quantifiable concentration of LTG solution, LTG-loaded micelles, and LTG-loaded mixed micelles were 55, 35, and 15 minutes and about 5,384, 16,500, and 25,245 (min⋅µg)/L in the hippocampus, respectively. CONCLUSION: The results revealed that LTG-loaded mPEG-PLA/TPGS mixed micelles enhanced the absorption of LTG at the nasal cavity and reduced the efflux of LTG in the brain, suggesting that the function of TPGS inhibited P-glycoprotein and LTG-loaded mPEG-PLA/TPGS mixed micelles had the potential to overcome refractory epilepsy.