Study on release mechanism of berberine hydrochloride-loaded carboxymethyl konjac glucomannan pellets for colonic delivery / 中国中药杂志

<p><b>OBJECTIVE</b>To study release mechanism of berberine hydrochloride (BH) from carboxymethyl konjac glucomannan pellets for colonic delivery.</p><p><b>METHOD</b>The pellets were prepared by ionotropic gelation technique. The effects of the kinds of enzyme and enzyme concentration of dissolution media on the release of BH and the erosion properties of the pellets were studied.</p><p><b>RESULT</b>Compared with the dissolution media without enzymes, the release of BH and the erosion of the pellets were increased obviously in the media with rat cecal and colonic content or beta-mannase, the degradation of the carrier material of pellets by enzymes was the main factor which result in the erosion of the pellets. With the increased of beta-mannase concentration, the release of BH and the erosion of the pellets increased, the amount relationships of the release of BH and the erosion of the pellets were approximately 1:1. The release of BH exhibit Peppas equation, the n value was more than 1.</p><p><b>CONCLUSION</b>The release mechanism of BH from the pellets was enzymatic erosion-controlled, which indicates the potential of the pellets to serve as a colon-specific drug delivery system.</p>

Comparison of kinetic behavior in both plasma and tissue after intravenous administration of alpha-asarone in lipid emulsion and aqueous solution in rats and mice / 中国中药杂志

<p><b>OBJECTIVE</b>To compare the pharmacokinetics and tissue distribution of alpha-asarone in lipid emulsion and aqueous solution for injection and study the feasibility of lipid emulsion of alpha-asarone as the parenteral drug delivery system.</p><p><b>METHOD</b>HPLC was used to determine the drug concentration in rat plasma and mice tissues after intravenous (i.v.) administration of lipid emulsion and aqueous solution of alpha-asarone at a single dose (40 mg x kg(-1)), respectively.</p><p><b>RESULT</b>The plasma concentration-time profiles of lipid emulsion and aqueous solution of alpha-asarone after intravenous administration of them are similar and the drug concentration-time data were fitted to a two-compartment open model. The results of tissues distribution showed that distribution contents of alpha-asarone from lipid emulsion and aqueous solution in vivo are similar in lungs but lipid emulsion increased the uptake in livers and spleens, and decreased the uptake in hearts and kidneys for alpha-asarone.</p><p><b>CONCLUSION</b>The plasma concentration-time profiles of alpha-asarone in lipid emulsion and aqueous solution are similar, but lipid emulsion significantly altered the tissue distribution of alpha-asarone, which may be beneficial to decrease its potential toxicity to heart and kidney.</p>

Studies on in vivo release of berberine hydrochloride from carboxymethyl konjac glucomannan pellets in rats / 中国中药杂志

<p><b>OBJECTIVE</b>To observe the absorption and concentration of berberine hydrochloride (BH) in gastric, entric, colonic tissue after intragastric administration of BH-containing carboxymethyl konjac glucomannan pellets for evaluating colon-specific drug delivery characteristics of the pellets.</p><p><b>METHOD</b>BH-containing carboxymethyl konjac glucomannan pellets (pellets group) and BH-containing carboxymethyl cellulose suspension (control group) were intragastric administrated to rats at the dose of 50 mg x kg(-1), respectively. A high performance liquid chromatography method determinated BH concentration in rat plasma and tissue. Drug delivery index (DDI) was calculated.</p><p><b>RESULT</b>The range of BH in plasma and tissue in rats were 0.025 2-2.52 mg x L(-1) (r = 0.999 2) and 0.126-25.22 mg x L(-1) (R > 0.99),respectively. The detection of BH in plasma and tissue were 10 microg x L(-1) and 8 microg x L(-1), respectively. The area under the curve (AUC(0 --> infinity)) in the plasma samples of pellets group was 0.477 times that of the control group; in the gastric, entric, colonic tissue, the AUC(0 --> infinity) of pellets group was as much as 0.187, 0.228, 2.00 times that of the control group, respectively. The DDI of the pellets was 0.392 4, 0.478 6, 4.193 in the gastric, entric, colonic tissue of the rat, respectively.</p><p><b>CONCLUSION</b>Carboxymethyl konjac glucomannan pellets may be a useful carrier of BH for colon-specific delivery.</p>

Study on drug release of gastrodin ion-activated nasal in situ gel in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To study on the drug release characteristics and mechanism of gastrodin ion-activated nasal in situ gel in vitro.</p><p><b>METHOD</b>Regularity and mechanism of the drug release of gastrodin nasal in situ gel were studied by using the diffusion cell model and the membrane-less dissolution model, respectively. A novel kinesis diffusion cell model was designed according to the characteristics of release environment of nasal cavity. It was used to investigate the effect of adhesiveness on the release of the in situ gel.</p><p><b>RESULT</b>Drug release of gastrodin nasal in situ gel followed the one order release model. Erosion rate of the gel was low and not linearly correlated with the release rate. Compared with gastrodin solution, the nasal in situ gel could increase release time and release amount.</p><p><b>CONCLUSION</b>Gastrodin in the nasal in situ gel is released mainly by diffusion rather than erosion. Release amount of the in situ gel in nasal cavity may be obviously increased because of its adhesiveness.</p>

Effect of several penetration enharcers on transdermal permeation and skin accumulation of artemether / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate penetration characteristics of artemether and the effect of different permeation enhancer on transdermal permeation of artemether through rat skin.</p><p><b>METHOD</b>The permeation experiments were performed using rat skin on modified Franz diffusion cells in vitro. The concentrations of artemether in receptor compartment at specified time points were determined by HPLC.</p><p><b>RESULT</b>The permeating ratio through human skin of artemether solution was Js (2.78 +/- 0.78) microg x cm(-2) x h(-1), the quantity of drug penetrated through and accumulated in the skin by the end of the experiment were (69.07 +/- 3.01) microg x cm(-2), (58.93 +/- 3.56) microg x cm(-2) respectively. Four different permeation enhancers can improve the transdermal permeation of artemether.</p><p><b>CONCLUSION</b>Artemether have the potential to be developed to new transdermal preparation.</p>

In vitro dexamethasone release from nanoparticles and its pharmacokinetics in the inner ear after administration of the drug-loaded nanoparticles via the round window / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the feasibility of local drug delivery into the inner ear using solid lipid nanoparticles (SLN) and evaluate its potential for inner ear disease treatment in terms of the pharmacokinetics of the delivered drug in the inner ear.</p><p><b>METHODS</b>Dexamethasone acetate (DA)-loaded SLN was prepared with Compritol 888 ATO as the matrix by means of hot dispersion-ultrasonic technique. A high-performance liquid chromatography (HPLC) was established for determining DA and dexamethasone (Dex). The pharmaceutical properties of DA-loaded SLN including the particle size, entrapment ratio and in vitro release were estimated. DA-loaded SLN was administered via intratympanic injection or intravenous injection in guinea pigs and Dex concentration in the perilymph was measured with HPLC for estimation of the pharmacokinetic parameters.</p><p><b>RESULTS</b>The mean diameter of the DA-loaded SLN was 106.8 nm with entrapment ratio of 83.8%, and the in vitro DA release from the nanoparticles well conformed to Weibull distribution, with sustained-release of DA from the SLN exceeding 6 days. After intravenous injection of DA-loaded SLN in guinea pigs, Dex failed to be detected in the perilymph. Compared with Dex-loaded in situ gel following intratympanic injection, the relative bioavailability of Dex in the perilymph was 504% following intratympanic injection of DA-loaded SLN, which also resulted in increased t(1/2) and mean residence time (MRT) by 0.5 and 1.9 folds respectively.</p><p><b>CONCLUSION</b>Nanoparticles can be a promising tympanic drug delivery system for topical drug administration in the treatment of inner ear diseases.</p>

In vitro evaluation of self-emulsifying drug delivery system of volatile oil from rhizome of Ligusticum chuanxiong / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the evaluation method for self-emulsifying drug delivery system of volatile oil from rhizome of Ligusticum chuanxiong (VOC SEDDS).</p><p><b>METHOD</b>The self-emulsifying ability, the efficiency of self-emulsification, the properties of emulsion, the dissolution of volatile oil from Rhizome of Ligusticum Chuanxiong and the stability of the emulsion were determined.</p><p><b>RESULT</b>The optimized formulation can fully emulsify in 5 min and the particle sizes were around 102 nm. Zeta potential was about -30 mV. The O/W emulsions were stable through centrifugation with high reproducibility. In vitro dissolution test indicated that over 80% of drug dissolved in 30 min and VOC SEDDS was stable under light and high temperature in 10 d.</p><p><b>CONCLUSION</b>VOC SEDDS has strong self-emulsifying ability, fine stability and high dissolution rate in vitro.</p>

Study on in vitro colon-specific enzymatic degradation performance of carboxymethyl konjac glucomannan / 中国中药杂志

<p><b>OBJECTIVE</b>In vitro enzymatic degradation of carboxymethy konjac glucomannan (CMKGM) were studied to evaluate the feasibility of CMKGM used as carrier materials to prepare colon-specific drug delivery systems.</p><p><b>METHOD</b>The solutions with rat gastrointestinal tract (GIT) contents or with commercial enzymes were chosen to stimulate in vivo GIT environment, respectively. Enzymatic degradation of CMKGM were studied by viscometic procedure. Degradation kinetics of CMKGM and konjac glucomannan (KGM) by enzymes, the effects of the degree of substitution (DS) of CMKGM and the pH of solution on its susceptibility to degradation were investigated.</p><p><b>RESULT</b>CMKGM were degraded mainly in the simulated cecal and colonic media, but not in the simulated gastric and enteric media. Degradation of KGM and CMKGM by enzymes obeyed Michaelis-Menton kinetics. CMKGM with lower DS were more susceptible substrates. CMKGM were more susceptible substrates in solution with pH 6. 0-6. 8.</p><p><b>CONCLUSION</b>CMKGM had colon-specific enzymatic degradation characteristics and could be used as carrier materials to prepare colon-specific drug delivery systems.</p>

Preparation and characterization of biotinylated chitosan nanoparticles / 药学学报

Biotinylated chitosan nanoparticles (Bio-CS-NP) were prepared for the active delivery to cancer cells and its characterization was investigated in this study. The preparation process included two steps. First, biotinylated chitosan ( Bio-CS ) was obtained through a reaction between sulfosuccinimidobiotin and chitosan (CS). Second, Bio-CS-NP were prepared by the precipitation of Bio-CS with sodium chloride solution. With a biotin reagent box, the conjugation densities of biotin on the surface of Bio-CS-NP were determined. The morphology and diameter of the nanoparticles were assayed by transmission electron microscope (TEM) and laser light scattering particle analyzer, respectively. The uptake of nanoparticles by human hepotacarcinoma HepG2 cells, for example, Bio-CS-NP and chitosan nanoparticles (CS-NP) without any modification, was quantitatively examined. The results indicated that the conjugation densities of biotin on the surface of Bio-CS-NP were 2.2 biotin CS. Bio-CS-NP were spherical, smooth on the surface. The average diameter was 296.8 nm. The polydispersion index was 0.155. The uptake of Bio-CS-NP by HepG2 cells was much higher than that of CS-NP (P < 0.05). It demonstrated that Bio-CS-NP can be applied as a new vehicle to actively deliver anticancer drugs to tumor cells. The method for the determination of biotin was simple and practical.

Study on drug release in vitro and rat intestinal absorption of resveratrol nanoliposomes / 中国中药杂志

<p><b>OBJECTIVE</b>To study the release feature of Res-nanoliposomes in vitro and clarify the difference in absorption of Res-nanoliposomes from varied intestinal segments and the absorptive mechanism in vivo.</p><p><b>METHOD</b>Dialytic method was used to determine resveratrol release rate of Res-nanoliposomes in vitro. An in situ rat perfusion method was used to investigate the intestinal absorption of Res-nanoliposomes.</p><p><b>RESULT</b>Resveratrol release from nanoliposomes in vitro fitted the log-normal distribution equation and had a property of sustained release. Compared with other intestinal segments, significantly high percentage of Res-nanoliposomes was absorbed in ileum (P < 0.001). The absorption rate constants (ka) of Res-nanoliposomes in intestine were not significantly different.</p><p><b>CONCLUSION</b>Res-nanoliposomes could sustain to release drug in vitro. The absorption was a first-order process with the passive diffusion mechanism. The Res-nanoliposomes could promote the absorption of Res in rat small intestine.</p>

Comparison of two preparation methods applied in tanshinone II(A)-loaded PLGA nanoparticles / 中国中药杂志

<p><b>OBJECTIVE</b>To optimize formulation of tanshinone II(A)-loaded PLGA nanoparticles and compare the difference of two methods in preparation and quality of nanoparticles.</p><p><b>METHOD</b>The two methods were nanoprecipitation method and emulsion-evaporation method. Single factor experiments and central composite design and response surface method were used to optimize the formulation of nanoparticles. The nanoparticles were characterized at size, morphology, entrapment efficiency, drug loading, drug recovery rate, crystallinity and drug release in vitro.</p><p><b>RESULT</b>The mean diameters were 225 nm and 183 nm, the entrapment efficiency were 95.49% and 87.99%, the drug loading were 2.03% and 0.16%, and the drug recovery rates were 38.42% and 17.59% respectively for nanoprecipitation method and emulsion-evaporation method.</p><p><b>CONCLUSION</b>Nanoprecipitation method was better than emulsion-evaporation method for preparation of tanshinone II(A)-loaded PLGA nanoparticles.</p>

Preparation of liposome entrapped vincristine sulfate and mitoxantrone chlorhydric acid / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the prepation of the liposome carried with vincristine sulfate (VCR) and mitoxantrone chlorhydric acid (MTO) and to evaluate the quality of the liposome.</p><p><b>METHOD</b>The liposome carried with VCR and MIT was prepared by pH-gradients method and reverse evaporation technique. HPLC was employed to determine VCR and MIT entrapping efficiency of liposomal. Laser particle analyzer was applied to determine the size and zeta potential of the liposomes carried with VCR and MTO.</p><p><b>RESULT</b>The mean diameter of the liposome carried with MIT and VCR was 72.22 nm, with the entrapping rate of 95.77% for VCR and 99.53% for MTO. The liposome had perfect shape.</p><p><b>CONCLUSION</b>The liposomes with high entrapping rate and small particle size had been prepared by pH-gradient method and reverse evaporation technique.</p>

Transdermal and lymph targeting transfersomes of vincristine / 药学学报

Vincristine (VCR) is mainly used to treat acute lymphocytic leukemia, Hodgkin and non-Hodgkin lymphoma in clinic with definite therapeutic effect. But the obvious neurotoxicity and local stimulation of which limit its clinic use. In order to increase the lymph targeting to enhance the curative effect and to lower the adverse reaction of VCR, the VCR loaded transfersomes (VCR-T) were prepared with dry-film and ultrasonic dispersing methods, and the corresponding pharmaceutical properties, pharmacokinetical characteristics and the targeting ability were studied. The average particle size of VCR-T prepared was 63 nm with an entrapment ratio of 59%. The in vitro transdermal research with modified Franz cell showed that VCR-T permeated through the skin in accordance with polynomial equation, and with an accumulation permeation percentage of 67.4% up to 12 h. An HPLC method was utilized to determine the pharmacokinetics and tissue distribution of VCR. Compared with the iv injection of VCR solution, the retention time of VCR in blood was extended by 12 times with VCR-T, and the targeting index in rat lymph was increased by 2.75 times. As a result, transfersomes could penetrate the skin and enter into the systemic circulation carrying VCR with good lymph targeting ability, which makes it probably a new lymphtic targeting drug delivery system.

Preliminary study on brain-targeted drug delivery via inner ear / 药学学报

The article investigates the feasibility of delivering drugs to brain via inner ear, and provides a novel route for delivering drugs to the brain tissues. Dexamethasone acetate (DA)-loaded solid lipid nanoparticles (SLN) was prepared by using Compritol 888 ATO as material. HPLC assays for the determination of DA, dexamethasone sodium phosphate (DSP) and dexamethasone (Dex) were developed, separately. DA-loaded SLN and DSP solution were administered after intratympanic injection (IT) or intravenous injection (IV). Perilymph ( PL) and cerebrospinal fluid (CSF) were collected periodically. The concentrations in PL and CSF were measured by HPLC, and used to estimate pharmacokinetic parameters of Dex in CSF. The AUC of Dex in CSF following IT DA-loaded SLN or DSP solution were respectively 2.5 and 4.3-fold higher than those following IV. After IT, DA-loaded SLN increased the AUC by 13 times and extended the MRT by 19 times, compared with the solution. Moreover, the AUC of Dex in PL following IT the SLN was 76% lower than that following IT the solution. Intra-cochlear administration shows great potential and offers a promising alternative to brain-targeted drug delivery.

Comparison of preparing two polylactide nanoparticles loaded lipophilic anti-cancer herb drug by nanoprecipitation method / 中国中药杂志

This paper introduced an experimental study of polylacticacid (PLA) nanoparticles of lipophilic anti-cancer herb drug using a precipitation method. Cucurbitacins (Cu) and Curcuminoids (Cur) were selected to be model drugs. They had similar solubility but their incorporation effects were significantly different: the average drug entrapment ratio, the average drug loading and the average drug recovery were 38.53%, 2.21% and 27.02% respectively; while those of Cur-PLA-NP were 94.36%, 14.35% and 91.23% respectively. To analyse the reason, drug incorporation process was investigated. By measuring solvent evaporation rate, ratio of drug PLA precipitates, drug distribution in system and entrapping ratio at different time of preparation, we found the difference of precipitation velocity of drug was the main reason. We also concluded that not all lipophilic drug can be well entrapped into PLA nanoparticle by nanoprecipitation method. The drug incorporation depended on the interations among drug, PLA and organic solvents, in addition to the solubility of the drug.

Preparation and characterization of transfersomes of three drugs in vitro / 中国中药杂志

<p><b>OBJECTIVE</b>To investigate the influence of drug properties on the encapsulation effiency (EE) and drug release of transfersomes for a proper transfersome preparation.</p><p><b>METHOD</b>To prepare the transfersomes of colchicines (CLC), vincristine sulfate (VCR) and mitoxantrone hydrochloride (DHAD) with the same materials and methods, and then measure their EE. To find out the relationship between drug properties like solubility, molecular weight and charges, and EE. To performe the drug release experiments of various types of transfersomes in vitro, and compare their differences.</p><p><b>RESULT</b>VCR and DHAD are lipophilic or hydrophilic, owing positive charges and large molecular weight, as a result, their EE are high, while CLC is amphipathic, neutral, and of small molecular weight, its EE is very low. As DHAD can insert into the membrane of transfersome, the drug release of DHAD-T in vitro is much slower than that of VCR-T.</p><p><b>CONCLUSION</b>To prepare transfersomes with high EE, drugs that are lipophilic or hydrophilic, high molecular weight and opposite charges to the membrane should be chosen. Interaction between drugs and membrane will influnce the rate of drug release.</p>

Study on the preparation of resveratrol chitosan nanoparticles with free amino groups on the surface / 中国中药杂志

<p><b>OBJECTIVE</b>To prepare resveratrol chitosan nanoparticles with free amine groups on the surface so as to conjugate ligands, which will actively target to special tissues or organs.</p><p><b>METHOD</b>The chitosan nanoparticles with free amine on the surface was prepared by sodium chloride precipitation. Nanoparticles with different solidification degrees were studied on turbidity, in vitro release, encapsulation efficiency, drug loading and diameter.</p><p><b>RESULT</b>The turbidity of nanoparticles with various solidification degrees decreased at different rates after ultrasonic or water bath heating treatment. All nanoparticles mentioned above obviously shew sustained release. The rate of release was slowed down with the increase of solidification agents. Solidification had no obvious effects on the encapsulation efficiency and drug loading. The diameter of chitosan nanoparticles with 200 microL solidification agents was 487 nm. The polydispersion was 0.144.</p><p><b>CONCLUSION</b>The diameter of the prepared nanoparticles was relatively small. The amine on the surface was free, which offered the possibility of designing the acive target drug delivery system.</p>

Study on preparation of konjac glucomannan-hydroxypropyl methyl cellulose compression coated tablets for colonic delivery and in vitro release / 中国中药杂志

<p><b>OBJECTIVE</b>Prepare konjac glucomannan-hydroxypropyl methyl cellulose (HPMC) compression coated tablets and study the effects of the formulation, technics and in vitro dissolution condition on drug release behavior to elevate the colon-specific effects of preparation.</p><p><b>METHOD</b>Berberine hydrochloride core tablets were prepared by wet granulation technique and konjac glucomannan-HPMC mixture as the coating layer were used with compression coated technique. The effects of the formulation and technics on drug release behavior were investigated by dissolution test. The erosion of coat layer during dissolution test was investigated.</p><p><b>RESULT</b>Drug almost not released in dissolution medium stimulating gastric and intestinal condition, and released completely by coating layer erosion and rupture by enzyme in stimulating colonic condition. Drug release decreased with decreasing the ratio of konjac glucomannan-HPMC and increasing coat weight (P < 0.05), compression force was not found to be a significant factor on drug release. Drug release increased with increasing the concentration of beta-mannase in dissolution medium (P < 0.05), rotation speed has no effect on drug release. The release of drug was correlative with erosion of coat layer. The mechanism of drug release were diffusion and erosion.</p><p><b>CONCLUSION</b>The konjac glucomannan-HPMC compression coated tablets was a promising delivery system for drugs to be delivered to the colon.</p>

Studies on characteristics of absorption and separation of traditional Chinese medicine compound prescription by macroporous resin / 中国中药杂志

<p><b>OBJECTIVE</b>Study the characteristics of absorption and separation of traditional Chinese medicine compound prescription using macroporous resin.</p><p><b>METHOD</b>Study the techniquecs and characteristics of absorption and separation of a sample by macroporous resin, which is composed of coptis root, rhubarb and common anemarrhena rhizome, containing alkaloid, anthraquinone and saponin.</p><p><b>RESULT</b>It is proved by qualitative and quantitative researches studies that after absorbed and separated by optimized technics process, most prime effective components or section fractions in traditional Chinese medicine compound prescription can be reserved maintained.</p><p><b>CONCLUSION</b>If the techniquecs of separation is properly designed, the same kind of macropore resin can absorbd and separate various effective components or section in traditional Chinese medicine compound prescription which have with different chemical structures efficiently.</p>

Release profile of compound liposomes entrapped with vincristine sulfate and mitoxantrone chlorhydric acid in vitro and their distribution in mice / 药学学报

<p><b>AIM</b>To study on the release profile in vitro and biodistribution in mice of the compound liposomes carried with vincristine sulfate (VCR) and mitoxantrone chlorhydric acid (MTO).</p><p><b>METHODS</b>The release behaviors of the VCR and MTO from compound liposomes were studied in vitro. HPLC was developed for the determination of the contents of VCR and MTO in tissues in mice.</p><p><b>RESULTS</b>The release time of VCR from compound liposome was 24 h and that from free drug (in control solution) was 6 h. The release of MTO from compound liposome was 0.05% after 288 h and release time of MTO from free drug (in control solution) was 12 h. The liposomes and free drugs were injected intravenously at same dose to mice. The elimination half-life time (T 1/2) in plasma of liposomal and free VCR were 0.16 h and 0.14 h, and the AUCs (0 - 48 h) of them were 2.69 (ug x g(-1)) x h and 1.58 (ug x g(-1)) x h, respectively. The elimination half-life times (T 1/2) in plasma of liposomal and free MTO were 21.6 h and 0.05 h and the AUCs (0 - 48 h) of them were 17.06 (ug x g(-1)) x h and 0.42 (ug x g(-1)) x h, respectively.</p><p><b>CONCLUSION</b>The compound liposome with high entrapping efficiency and small particle size could be prepared by pH-gradients method and reverse evaporation technique. Two drugs were sustained-released from the compound liposome. Mice tail intravenous injection of compound liposomes showed that compound liposome prolonged the retention time and improved the concentration of MTO and VCR in the blood circulation system compared to control. In the mean time, compound liposome reduced the concentration of the MTO and VCR in heart, lung, kidney etc. These observations indicated that compound liposome could improve anticancer activity and reduce side effect.</p>