Prospective of guar gum and its derivatives as controlled drug delivery systems

Guar gum is a non-ionic polysaccharide that is found abundantly in nature and has many properties desirable for drug delivery applications. However, due to its high swelling characteristics in aqueous solution, the use of guar gum as delivery carriers is limited. Guar gum can be modified by derivatization, grafting and network formation to improve its property profile for a wide spectrum of biomedical applications. This review article is aimed at focusing the recent efforts and developments on guar gum and its derivatives as colon-specific, antihypertensive, protein and transdermal drug delivery systems. Based on the literatures reviewed, it is concluded that guar gum and its derivatives in the various forms such as coatings, matrix tablets, hydrogels and nano/microparticles can be exploited as potential carriers for targeted drug delivery.     

纳米枸杞多糖合生元靶向微生态调节剂的制备及质量研究

目的制备合生元结肠靶向微生态调节剂,并建立其质量标准。方法球磨法制备枸杞多糖纳米粒,并将其与双歧杆菌、结肠粘附材料按一定比例装填入结肠靶向胶囊中,制备成合生元结肠靶向微生态调节剂;苯酚-硫酸法测定制剂中多糖含量,平板活菌计数法检测制剂中活菌数量。结果球磨法制备的枸杞多糖纳米粒成类球形,表面圆整,无粘连,80％粒径集中在464nm;合生元结肠靶向微生态调节剂符合2010版药典对胶囊剂的质量要求。结论按本法制备的合生元结肠靶向微生态调节剂安全可靠,其质量符合2010版药典对胶囊剂的质量要求。     

Structural assignment of a heteropolysaccharide isolated from the gum of Cochlospermum religiosum (Katira gum)

A heteropolysaccharide isolated from the gum (Katira) of Cochlospermum religiosum was found to consist of D-galactose, D-galacturonic acid and L-rhamnose in a molar ratio 2:1:3. Structural assignment of the polysaccharide was carried out using total acid hydrolysis, methylation analysis, periodate oxidation, Smith degradation and NMR studies (1H, 13C, DQF-COSY, TOCSY, NOESY, HMBC and HSQC) and the repeating unit of the polysaccharide was established as [Formula: see text].     

Eudragit-coated pectin microspheres of 5-fluorouracil for colon targeting

An objective of the present investigation was to prepare and evaluate Eudragit-coated pectin microspheres for colon targeting of 5-fluorouracil (FU). Pectin microspheres were prepared by emulsion dehydration method using different ratios of FU and pectin (1:3 to 1:6), stirring speeds (500–2000 rpm) and emulsifier concentrations (0.75%–1.5% wt/vol). The yield of preparation and the encapsulation efficiencies were high for all pectin microspheres. Microspheres prepared by using drug:polymer ratio 1:4, stirring speed 1000 rpm, and 1.25% wt/vol concentration of emulsifying agent were selected as an optimized formulation. Eudragit-coating of pectin microspheres was performed by oil-in-oil solvent evaporation method using coat: core ratio (5:1). Pectin microspheres and Eudragit-coated pectin microspheres were evaluated for surface morphology, particle size and size distribution, swellability, percentage drug entrapment, and in vitro drug release in simulated gastrointestinal fluids (SGF). The in vitro drug release study of optimized formulation was also performed in simulated colonic fluid in the presence of 2% rat cecal content. Organ distribution study in albino rats was performed to establish the targeting potential of optimized formulation in the colon. The release profile of FU from Eudragit-coated pectin microspheres was pH dependent. In acidic medium, the release rate was much slower; however, the drug was released quickly at pH 7.4. It is concluded from the present investigation that Eudragit-coated pectin microspheres are promising controlled release carriers for colon-targeted delivery of FU. Published: February 16, 2007     

In vivo evaluation of modified gum karaya as a carrier for improving the oral bioavailability of a poorly water-soluble drug,nimodipine

This work examines the influence of modified gum karaya (MGK) on the oral bioavailability of a poorly water-soluble drug, nimodipine (NM), in comparison with that of gum karaya (GK). A cogrinding method was selected to prepare mixtures of NM and GK or MGK in a 1:9 ratio (NM:GK/MGK). Differential scanning calorimetry (DSC), Fourier transmission infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), solubility studies, and in vitro release studies were performed to characterize the properties of the cogrinding mixtures. No drug-carrier interactions were found, as confirmed by DSC and FT-IR studies. The XRD study revealed that the crystallinity of NM was identical in both the cogrinding mixtures and was decreased when compared to that of physical mixtures or pure NM. The in vitro release rate of NM from both cogrinding mixtures was significantly higher than that of physical mixtures or pure NM. The in vivo study revealed that the bioavailability of NM from pure drug was significantly lower when compared to the cogrinding mixtures. The oral bioavailability was found to be NM powder < cogrinding mixtures of NM and GK < cogrinding mixtures of NM and MGK < NM solution. It can be inferred from the above results that MGK, an economical carrier, could be used for the dissolution enhancement of NM.     

槐豆胶与黄原胶的协效性研究

对槐豆胶与黄原胶的协效性进行了研究,结果表明,槐豆胶和黄原胶有较高的协效性,其最佳配比（重量比）为2：8;当混合液浓度达到0.5%-0.6%时形成凝胶,因此槐豆胶可作为黄原胶的增稠剂和凝胶剂。     

A double prodrug system for colon targeting of benzenesulfonamide COX-2 inhibitors

The design, synthesis and delivery potential of a new type of benzenesulfonamide cyclo-oxygenase-2 (COX-2) inhibitor prodrug is investigated using celecoxib. The approach involves a double prodrug that is activated first by azoreductases and then by cyclization triggering drug release. We studied the intramolecular aminolysis of the acylsulfonamide. The cyclization was surprisingly rapid at physiological pH and very fast at pH 5. The prodrug is activated specifically under conditions found in the colon but highly stable in the presence of human and rodent intestinal extracts. Finally, the prototype with celecoxib was transported much more slowly in the Caco-2 transepithelial model than the parent. The design therefore shows significant promise for the site specific delivery of benzenesulfonamide COX-2 inhibitors to the colon.     

New targeting system for antimycotic drugs: beta-glucosidase sensitive amphotericin B-star poly(ethylene glycol) conjugate

A new targeting potentially intravenous conjugate Amphotericin B (AMB)–star poly(ethylene glycol) (sPEG) (M = 25,160) has been synthesized and characterized. It contains a β-d-glucopyranoside molecular switch which is sensitive to β-glucosidases (E.C.3.2.1.21). The β-glucosidase-catalyzed release of AMB from the polymeric carrier was proved in vitro by means of spectrophotometry and HPLC.     

An in vitro study of the stereoselective dissolution of (rac)-verapamil from two sustained release formulations

The stereoselectivity of the in vitro dissolution of two commercially available sustained release formulations of rac-verapamil (rac-VER) has been investigated. The studies were carried out using a single-tablet continuous-flow apparatus and the concentrations of R- and S-VER released from the formulations were measured using enantioselective chromatography on a high performance liquid chromatography (HPLC) chiral stationary phase containing immobilized α₁-acid glycoprotein (Chiral AGP-column). The data from this study demonstrates that the two formulations have different dissolution profiles and that the amount of drug dissolved was highly dependent on pH. In addition, between pH 3 and 8, the total cumulative amount of R-VER released was greater than the amount of S-VER and a statistically significant difference (P < 0.01) was detected at pH 6. The results of this study indicate that bioavailability and bioequivalency studies should consider the possibility of enantioselective dissolution when racemic compounds are present in the formulations. © 1993 Wiley-Liss, Inc.     

Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery

A great challenge for gene therapy is to develop a high efficient gene delivery system with low toxicity. Nonviral vectors are still attractive although the current agents displayed some disadvantages (i.e., low transfection efficiency, high toxicity). To overcome the high toxicity of poly(ethylene imine) (PEI) and low transfection efficiency of PEGylated PEI (PEG-PEI), we linked a cell specific target molecule folate (FA) on poly(ethylene glycol) (PEG) and then grafted the FA-PEG onto hyperbranched PEI 25 kDa. The FA-PEG- grafted-hyperbranched-PEI (FA-PEG-PEI) effectively condensed plasmid DNA (pDNA) into nanoparticles with positive surface charge under a suitable N/P ratio. Tested in deferent cell lines (i.e., HEK 293T, glioma C6 and hepatoma HepG2 cells), no significant cytotoxicity of FA-PEG-PEI was added to PEG-PEI. More importantly, significant transfection efficiency was exhibited in FA-targeted cells. Reporter assay showed that FA-PEG-PEI/pDNA complexes had significantly higher transgene activity than that of PEI/pDNA in folate-receptor (FR) positive (HEK 293T and C6) cells but not FR-negative (HepG2) cells. These results indicated that FA-PEG-PEI might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, and relatively high gene transfection efficiency.     

Stereospecific determination of the in vitro dissolution of modified release formulations of (±)-verapamil

The determination of the in vitro dissolution profiles of three different modified-release formulations of (±)-verapamil were determined and compared to a reference (Calan SR). The determination of (±)-verapamil utilized a microwave-facilitated derivatization reaction with an enantiomerically pure reagent followed by measurement of drug by reversed-phase high-performance liquid chromatography (HPLC). The dissolution profile of each of the four modified-release formulations was followed for the first hour in simulated gastric fluid (pH 1.2) and then in simulated intestinal fluid (pH 7.5) for up to a total of 12 h. The resulting dissolution profiles of each modified-release formulation suggested that only one of the three test formulations had a similar dissolution to the Calan SR reference. Interestingly, the (S:R)-enantiomer ratios of two of the test products were significantly different from unity, and the third test product was also significantly different from unity if 4 out of 5 outliers were omitted. It is suggested that dissolution testing of modified-release formulations containing chiral active ingredients must be stereospecific in order to discern whether a drug-excipient interaction occurs. Additionally, it may be suggested that dissolution techniques relying more upon diffusion of medium through the tablet matrix, rather than erosion of the tablet, may accentuate enantiomeric differences in release rates. © 1993 Wiley-Liss, Inc.     

Mechanisms by which docosahexaenoic acid and related fatty acids reduce colon cancer risk and inflammatory disorders of the intestine

A growing body of epidemiological, clinical, and experimental evidence has underscored both the pharmacological potential and the nutritional value of dietary fish oil enriched in very long chain n − 3 PUFAs such as docosahexaenoic acid (DHA, 22:6, n − 3) and eicosapentaenoic acid (EPA, 20:5, n − 3). The broad health benefits of very long chain n − 3 PUFAs and the pleiotropic effects of dietary fish oil and DHA have been proposed to involve alterations in membrane structure and function, eicosanoid metabolism, gene expression and the formation of lipid peroxidation products, although a comprehensive understanding of the mechanisms of action has yet to be elucidated. In this review, we present data demonstrating that DHA selectively modulates the subcellular localization of lipidated signaling proteins depending on their transport pathway, which may be universally applied to other lipidated protein trafficking. An interesting possibility raised by the current observations is that lipidated proteins may exhibit different subcellular distribution profiles in various tissues, which contain a distinct membrane lipid composition. In addition, the current findings clearly indicate that subcellular localization of proteins with a certain trafficking pathway can be subjected to selective regulation by dietary manipulation. This form of regulated plasma membrane targeting of a select subset of upstream signaling proteins may provide cells with the flexibility to coordinate the arrangement of signaling translators on the cell surface. Ultimately, this may allow organ systems such as the colon to optimally decode, respond, and adapt to the vagaries of an ever-changing extracellular environment.     

Relationship between Cell Localization of Sesbania gum and Its Viscosity

The observation by transmission and scanning electronic microscopy on the endosperm cells from mature and developing seeds of Sesbania cannabina shows that the Sesbania gum after its synthesis is not secreted out of cells, it is accumulated inside the cells. The viscosity determination of different size of granules demonstrates that, the larger the size of granules, dm lower the gum viscosity, on the contrary, the smaller the size, the higher the viscosity. This result is in agreement with the localization of gum inside the cells. In addition, the total Content of saccharide and insoluble substances for different size granules was also determined, These results provide the need of small size of gum granules in the process of production with tile evidence of gum localization inside the endosperm cells of Sesbania seeds.     

Undesired versus designed enzymatic cleavage of linkers for liver targeting

A design for the selective release of drug molecules in the liver was tested, involving the attachment of a representative active agent by an ester linkage to various 2-substituted 5-aminovaleric acid carbamates. The anticipated pathway of carboxylesterase-1-mediated carbamate cleavage followed by lactamization and drug release was frustrated by unexpectedly high sensitivity of the ester linkage toward hydrolysis by carboxylesterase-2 and other microsomal components.     

黄原胶发酵液纯化精制研究

溶剂法直接提取的黄原胶产品含有大量菌体蛋白和色素杂质,总氮含量高、透明度差、色泽暗深。通过中性蛋白酶处理发酵液,使成品含氮量下降５６．５％;通过Ｎａ２ＳＯ３漂白液,使产品色泽大为改善。实验得出最佳酶解条件：发酵液稀释１倍,温度４４℃、ｐＨ７,加酶量１００ｕ／ｇ发酵液,作用时间２．５ｈ;最佳Ｎａ２ＳＯ３漂白条件：温度２０￣３０℃,ｐＨ５￣６,Ｎａ２ＳＯ３用量为１％（ｗ／ｗ）,作用时间１￣１．５ｈ。     

Impact of the extrusion process on xanthan gum behaviour

Processing xanthan gum by extrusion and subsequent drying produces a biopolymer showing particulate, rather than molecular behaviour in aqueous solution. This form of xanthan disperses very readily to give a viscosity that is strongly dependent on salt concentration. On heating above the temperature of the order-disorder transition as determined by calorimetry, there is a viscosity transition that is indicative of the irreversible loss of the particulate structure. It is suggested that the extrusion process melts and aligns xanthan macromolecules. On cooling reordering will occur but in the highly concentrated environment in the extruder ( approximately 45% water w/w), inter-molecular association between neighbouring macromolecules cannot proceed to completion due to kinetic trapping. As a consequence a network structure is created maintained by associations involving ordered regions. A xanthan solution can be prepared from this particulate material by dispersing and subsequent heating far more readily than can be achieved with non-processed xanthan.     

In vitro and in vivo evaluation of guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride

The objective of the study was to develop guar gum matrix tablets for oral controlled release of water-soluble diltiazem hydrochloride. Matrix tablets of diltiazem hydrochloride, using various viscosity grades of guar gum in 2 proportions, were prepared by wet granulation method and subjected to in vitro drug release studies. Diltiazem hydrochloride matrix tablets containing either 30% wt/wt lowviscosity (LM1), 40% wt/wt medium-viscosity (MM2), or 50% wt/wt high-viscosity (HM2) guar gum showed controlled release. The drug release from all guar gum matrix tablets followed first-order kinetics via Fickian-diffusion. Further, the results of in vitro drug release studies in simulated gastrointestinal and colonic fluids showed that HM2 tablets provided controlled release comparable with marketed sustained release diltiazem hydrochloride tablets (D-SR tablets). Guar gum matrix tablets HM2 showed no change in physical appearance, drug content, or in dissolution pattern after storage at 40°C/relative humidity 75% for 6 months. When subjectd to in vivo pharmacokinetic evaluation in healthy volunteers, the HM2 tablets provided a slow and prolonged drug release when compared with D-SR tablets. Based on the results of in vitro and in vivo studies it was concluded that that guar gum matrix tablets provided oral controlled release of water-soluble diltiazem hydrochloride. Published: June 30, 2005     

山樱桃树胶中的黄酮类成分研究

从蔷薇科植物山樱桃的树胶中分离得到4个具有不同结构类型的黄酮类成分,经现代波谱学方法鉴定为genistein(Ⅰ),sakuranetin(Ⅱ),neosakuranin(Ⅲ)和prunetinoside(Ⅳ),所有成分均系首次从该植物中分离得到。     

Rheological properties of guar gum and hydroxyethyl guar gum in aqueous solution

The rheological properties of aqueous solutions of guar gum (GG) and hydroxyethyl guar gum (HEG) have been investigated. The flow properties of these polysaccharide solutions were studied at the shear rate in the range 1.5–1310s⁻¹ using a Rheotest-2 viscometer. The flow of these polysaccharide solutions was described by equation of state based on Cross model. The basic rheological parameters, like zero shear rate viscosity (η_o), elasticity modulus (G_o) and relaxation time (gl_o) were calculated using simple and established relations. Master viscosity curves indicated that the molecular weight distribution of native guar gum has been changed by hydroxyethylation under specified reaction conditions. The effect of concentration and temperature on η_o and λ_o has been studied, and the relations among these were established by simple equations.