Biocompatible and biodegradable nanoparticles for enhancement of anti-cancer activities of phytochemicals / 中国天然药物

Many phytochemicals show promise in cancer prevention and treatment, but their low aqueous solubility, poor stability, unfavorable bioavailability, and low target specificity make administering them at therapeutic doses unrealistic. This is particularly true for (-)-epigallocatechin gallate, curcumin, quercetin, resveratrol, and genistein. There is an increasing interest in developing novel delivery strategies for these natural products. Liposomes, micelles, nanoemulsions, solid lipid nanoparticles, nanostructured lipid carriers and poly (lactide-co-glycolide) nanoparticles are biocompatible and biodegradable nanoparticles. Those nanoparticles can increase the stability and solubility of phytochemicals, exhibit a sustained release property, enhance their absorption and bioavailability, protect them from premature enzymatic degradation or metabolism, prolong their circulation time, improve their target specificity to cancer cells or tumors via passive or targeted delivery, lower toxicity or side-effects to normal cells or tissues through preventing them from prematurely interacting with the biological environment, and enhance anti-cancer activities. Nanotechnology opens a door for developing phytochemical-loaded nanoparticles for prevention and treatment of cancer.

Comparison of the characteristics of several polymer materials used in hydrophilic matrix tablets / 药学学报

Pure and drug hydrophilic matrix tablets were prepared by direct compression method with theophylline as a model drug. The characteristics of four hydrophilic matrix polymers, hydroxypropylmethylcellulose (HPMC), polyethylene oxide (PEO), sodium alginate (NaAlg) and xanthan gum (XG), were compared by investigating the water absorption, swelling, erosion and gel layer strength. The sequence of water absorption rate was XG > NaAlg (H) > PEO > NaAlg (L) > HPMC; The sequence of swelling index was XG > PEO > HPMC > NaAlg; The sequence of erosion rate was NaAlg (L) > NaAlg (H) > PEO80 > PEO200 > PEO300 > XG approximately PEO400 approximately K4M > K15M > PEO600 approximately K100M; The sequence of the gel layer strength was PEO > HPMC > XG > NaAlg. For the PEO and HPMC matrix tablets, with the polymer molecular weight increased, the drug release mechanism was gradually transferred from mainly depending on the erosion to the diffusion; for SAL matrix tablets, the drug release mainly depends on erosion mechanism; and for XG matrix tablets, the drug release mainly depends on non-Fick diffusion mechanism. Comparison of the performance difference between the polymer materials will contribute to rational design and prediction of drug release behaviors from matrix tables and ultimately to achieve clinical needs.

Optimization of a floating osmotic pump system of dipyridamole using central composite design-response surface methodology / 药学学报

A new type of floating osmotic pump of dipyridamole was designed in this paper. Apparatus three (Chinese Pharmacopeia 2005, appendix XD) was employed for in vitro dissolution test in order to evaluate the release and floating behavior in a same experiment. The system was optimized using central composite design-response surface methodology; where similarity factor (f2) between the dissolution profile of prepared formulation and the target dissolution profile was taken as dependent factor, usage amount of polyoxyethylene (X1, mg), NaCl (X2, mg) and pore former (PEG4000, X3, %) were taken as independent factors. The optimization model was f2 = -29.3 + 2.35X3 - 0.123X1(2) - 0.046X2(2) + 0.145X1X2 (R = 0.996). It was found that the dissolution profile could match the target dissolution profile under the condition of weight gain 8%-9%, X1 (20-34), X2 (30-57), X3 = 50. It is also found that the minimum usage percentage of pore former is 35.1%. The prediction results of the optimization model were good in the experiments.

Study on in vitro release empirical method and the release mechanism of budesonide colonic localization tablet / 药学学报

The three-step dissolution experiment was established to investigate the in vitro release of budesonide colon-specific tablet and to elucidate the drug release mechanism by fitting to different mathematical models. The physiological parameters of stomach, small intestine and colon such as pH value, intestinal flora, specific organic enzyme, vermiculation and conveying time were mimicked to plot the in vitro dissolution, separately. Sample were taken at predetermined time intervals in 24 h and the accumulated drug releases were determined by using HPLC method. Drug release curves of the localization tablets were fitted to various mathematical models. It shows that no drug release was found in 2 h. About 5% release was determined after 6 h while 77.5% accumulated release was reached within 24 h. Drug release from the in house formulation fitted well into first-order model. The three-step dissolution method could be used to evaluate the colon-specific characteristics of budesonide colonic localization tablet. The drug release behavior of the localization tablet conforms to the drug release mechanisms of controlled porosity osmotic pump where osmotic pressure is the main driving force for controlled delivery of drugs.

Tissue distribution of solid lipid nanoparticles loaded garlic oil in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the tissue distribution of the diallyl disulfide (DADS) and diallyl trisulfide (DATS) in solid lipid nanoparticles loaded garlic oil (GO-SLN) in rats.</p><p><b>METHOD</b>The gas chromatography-electron capture detection (GC-ECD) method was established to determined the DADS and DATS simultaneously in the biological samples of rats after administration of 0.5 mL garlic oil injection or GO-SLN (containing about 10 mg garlic oil) via jugular vein cannula. The conditions for gas chromatographic separation were as follows. The oven temperature was set at 110 degrees C and maintained for 15 min. Temperatures at the injection port and detector were 180 degrees C and 300 degrees C, respectively. Ultra-pure nitrogen (purity > 99.999%, Shenyang Kerui Special Gases Co. Ltd., China) was used as a carrier gas and made-up gas at flow-rates of 1 mL x min(-1) and 60 mL x min(-1), respectively. All injections were carried out in the split injection mode with a split ratio of 1:10.</p><p><b>RESULT</b>The GC-ECD method was fit for determing the concentration of DADS and DATS in garlic oil. The distribution character of GO-SLN in rats had changed to some extent and the concentration of GO-SLN in tissues was higher than that of GO-Injection.</p><p><b>CONCLUSION</b>The SLN can elevate the passive targeting of drugs and lengthen their action time in tissues.</p>

Preparation of PEG-modified nanostructured lipid carriers loaded with hydroxycamptothecin and tissue distribution in mice / 药学学报

Hydroxycamptothecin (HCPT) loaded PEG modified nanostructured lipid carriers (HCPT-PEG-NLC) and nanostructured lipid carriers (HCPT-NLC) were prepared by melt emulsification and homogenization method. The morphology, particle size and encapsulation efficiency of them were investigated. HCPT concentrations in plasma, heart, liver, spleen, lung, kidney and ovary were determined after iv of HCPT injection, HCPT-PEG-NLC and HCPT-NLC in mice. The targeting indexes of HCPT-PEG-NLC and HCPT-NLC were calculated. The transmission electron microscope imaging showed that HCPT-PEG-NLC and HCPT-NLC exhibited a spherical shape. The particle sizes of them were (88.6 +/- 22.5) and (127.2 +/- 43.4) nm. The encapsulation efficiency were (90.51 +/- 3.29)% and (84.37 +/- 2.81)%, respectively. After iv injection into the tail vein of mice, HCPT plasma concentrations of HCPT-PEG-NLC and HCPT-NLC were higher than that of HCPT injection at each sampling time. They also showed longer elimination time in every tissue. HCPT-NLC accumulated in endothelial system (RES), Re and Ce of it in liver and spleen were significantly higher than HCPT-PEG-NLC. HPCT-PEG-NLC prolonged circulation time and increased bioavailability of HCPT. MRT and AUC0-24 h of it were 19.80 and 17.02 times higher than those of HCPT injection. It also significantly reduced phagocytosis of RES, and showed lung targeting effect (Re and Ce were 14.51 and 41.35). To summarize, HCPT-PEG-NLC could prolong the circulation time of HCPT in vivo, and had the lung targeting effect. It was a promising carrier to increase therapeutic effect of HCPT in treating lung cancer.

Design and in vitro evaluation of self-microemulsifying drug delivery systems for piroxicam / 药学学报

Self-microemulsifying drug delivery systems (SMEDDS) were developed to overcome the problems of delivery and administration of piroxicam, a drug with low bioavailability and gastrointestinal irritation, The in vitro properties of it were assessed. The solubility of piroxicam in several oils and surfactants was determined, and the compatibility of various oils and surfactants was investigated. Ternary phase diagrams were constructed to optimal area of microemulsion, and the influence of different oily phases, surfactants and co-surfactants was studied. The droplet size and dissolution of optimal formulation were determined to prove that the dosage form is a useful delivery system for piroxicam. In the optimized piroxicam SMEDDS, cinnamic alcohol was selected that gave the maximal solubility to piroxicam. Labrafil M 1944CS, Cremophor EL and Transcotol P were used as oils, surfactant and co-surfactant, respectively. Droplet size and distribution of three piroxicam SMEDDS formulations were (32.2 +/- 5.0), (40.1 +/- 6.4), (81.9 +/- 12.2) nm individually. And the releasing of piroxicam was rapid and complete. The optimized SMEDDS for piroxicam was obtained.

The pharmacokinetics and bioequivalence of acipimox sustained-release tablets after a single and multiple oral administration in healthy dogs / 药学学报

<p><b>AIM</b>To study the pharmacokinetics and bioequivalence of acipimox sustained-release tablets (SRT) after a single and multiple oral dose in healthy dogs.</p><p><b>METHODS</b>The plasma concentrations of of SRT and reference capsules with a single and multiple oral doses.</p><p><b>RESULTS</b>The drug concentration-time profiles fitted to a noncompartment model. After a single dose administration of sustained-release tablets and capsules, the pharmacokinetic parameters were as follows: AUC were (158 +/- 30) and (147 +/- 37) microg x h x mL(-1); Tmax were (4.3 +/- 0.8) and (2.6 +/- 1.3) h; Cmax were (29 +/- 6) and (42 +/- 10) microg x mL(-1); T(1/2) were (2.3 +/- 0.7) and (1.60 +/- 0.10) h; MRT were (6.0 +/- 0.8) and (3.9 +/- 0.7) h, respectively. The relative bioavailability of the sustained-release tablet was (108 +/- 16) %. After a multiple oral administration of sustained-release tablets and capsules, the pharmacokinetic parameters were as follows: AUC were (209 +/- 23) and (195 +/- 26) microg x h x mL(-1); Tmax were (6.3 +/- 0.8) and (3.4 +/- 1.5) h; Cmax were (27 +/- 4) and (36 +/- 5) microg x mL(-1); Cmmin were (2.2 +/- 1.0) and (0.20 +/- 0.20) microg x mL(-1); Cav were (8.7 +/- 1.0) and (8.1 +/- 1.1) micro x mL(-1); FI were (293 +/- 73) % and (448 +/- 91) % , respectively. The relative bioavailability of the sustained-release tablet was (114 +/- 19) %.</p><p><b>CONCLUSION</b>The results of two one-side test from single dose administration shown that two preparations were bioequivalent. The Cmax of sustained-release tablet was lower than that of capsules, while the Tmax and MRT of sustained-release tablet were higher than that of capsule, which indicating a good retarding effect. The results from multiple dose administration also shown that two preparations were bioequivalent and the DF of sustained-release tablet was significant lower than that of capsule.</p>

The erosion behaviour of matrix tablets using polyethylene oxide matrices as hydrophilic polymer / 药学学报

<p><b>AIM</b>To study the erosion behaviour during dissolution of matrices using different molecular weight polyethylene oxide (PEO) as hydrophilic polymer.</p><p><b>METHODS</b>PEO hydrophilic matrix tablets with no added drug and excipients were prepared by direct compression method. The erosion rates of matrices comprised of pure or blending PEO polymers were evaluated in distilled water at (37 +/- 0.5) degrees C with rotating rate of 50 r x min(-1). The relationship between PEO molecular weight and erosion rate of matrices was investigated by experimental and mathematical model methods.</p><p><b>RESULTS</b>The gravimetric erosion experimental results indicated that the power-law relationship which relates the polymer erosion rate and weight average molecular weight: k infinity (M(w)) -1.30 4 was proved to have great potential utility in predicting the degree of polymer erosion of matrices comprised of either intermediate molecular weight (97. 98 x 10(4) - 553. 36 x 10(4)) or blends of lower and higher molecular weight polymers. Based on the semiempirical equation for mass transfer rate: Jp = (fp < Dp > (2/3) v (-1/6) omega (1/2)) C(p,dis), a theoretical mathematic model was developed for describing the relationship between PEO erosion rate and PEO weight average molecular weight: Jp infinity M(-1.241), where the exponent of -1. 241 was very close to the exponent of - 1. 130 4 obtained from practical determination.</p><p><b>CONCLUSION</b>PEO was proved to be a good candidate of hydrophilic polymer and appeared to have great potential for controlled release applications. The mathematic model presented together with the utilization of the erosion behaviour discussed in our study could provide a guide line to predict the degree of polymer erosion for other intermediate polymer grades and / or mixture of the polymers utilized in this study, which could play an active role in designing PEO hydrophilic sustained delivery systems.</p>

Studies on the influencing factors on the drug release from sodium alginate matrices / 药学学报

<p><b>AIM</b>To investigate the in vitro influencing factors on drug release from matrices with sodium alginate as the hydrophilic polymer.</p><p><b>METHODS</b>Sodium alginate hydrophilic matrix tablets were prepared by direct compression method with theopylline as a model drug. The in vitro influencing factors on drug release behavior from matrices were studied by investigating the swelling, water uptake and erosion characteristics of pure sodium alginate matrices.</p><p><b>RESULTS</b>The results showed that drug release rate and drug release mechanism were both related to the viscosity of sodium alginate used in matrices, pH values and ionic strength of dissolution media and rotation speeds.</p><p><b>CONCLUSION</b>Sodium alginate can be tailor-made to suit the demands of applicants in sustained delivery systems as a good candidate of hydrophilic polymer.</p>