Bioequivalence decision for nanoparticular iron complex drugs for parenteral administration based on their disposition.

Although parenteral iron products have been established to medicinal use decades before, their structure and pharmacokinetic properties are not fully characterized yet. With its' second reflection paper on intravenous iron-based nano-colloidal products (EMA/CHMP/SWP/620008/2012) the European Medicine Agency provided an extensive catalogue of methods for quality, non-clinical and pharmacokinetic studies for the comparison of nano-sized iron products to an originator (EMA, 2015). For iron distribution studies, the reflection paper assumed the use of rodents. In our tests, we used a turkey fetus model to investigate time dependent tissue concentrations in pharmacological and toxicological relevant tissues liver, heart and kidney. We found turkey embryos to be a suitable alternative to rodents with high discriminatory sensitivity. Clear differences were found between equimolar doses of iron products with hydroxyethyl amylopectin, sucrose, dextrane and carboxymaltose shell. A linear dose dependency for the tissue accumulation was also demonstrated.

In vitro digestion rate of fully gelatinized rice starches is driven by molecular size and amylopectin medium-long chains.

In current study, the effects of starch fine molecular structures on its in vitro digestibility at fully gelatinized stage were investigated. The digestion kinetics of 15 fully gelatinized rice starches were obtained and correlated with starch chain-length distributions and molecular size distributions. Both logarithm of slopes and parallel first-order kinetic model were applied to fit the digestion curves to a few kinetics-based parameters. Result showed there were two simultaneous digestion fractions (fast versus slow) for fully gelatinized rice starches. The rate constants of slowly-digestible fraction significantly correlated with starch molecular sizes, especially with that of amylopectin molecules. Hydrodynamically larger amylopectin molecules tend to contain more shorter branches but less long chains. This slows down the starch hydrolysis by α-amylase while the action of AMG is less antagonistically hindered, increasing overall digestion rate. This study provides important information for rice breeders and manufacturers to develop rice products with reduced starch digestibility.

Molecular-structure evolution during in vitro fermentation of granular high-amylose wheat starch is different to in vitro digestion.

This study investigates the evolution of the distributions of whole molecular size and of chain length of granular wheat starches (37 ~ 93% amylose content), subjected to in vitro fermentation with a porcine faecal inoculum or digestion with pancreatic enzymes. The results showed that the molecular structures of high-amylose starch (HAS) unfermented residues largely remained unchanged during the fermentation process, while wild-type starch (37% amylose content) showed a preferential degradation of the amylopectin fraction. In contrast, under simulated digestion conditions, the undigested residues of HAS showed structural changes, including a decrease in amylose content, a shift of amylose peak position towards lower degrees of polymerisation, and an enzyme-resistant fraction. These changes of starch structure are likely to be dependent on the different starch-degrading enzyme activities present in pancreatic vs. microbial systems. Molecular changes in response to fermentation metabolism revealed by size-exclusion chromatography can help understand the microbial utilization of resistant starch.

Stability and bioavailability of vitamin D3 encapsulated in composite gels of whey protein isolate and lotus root amylopectin.

A gel delivery system was developed in the present work using whey protein isolate and lotus root amylopectin via regulating pH. The texture, thermodynamics, rheology and microstructure of gels were evaluated. Results showed that pH at 7.0 induced a more compact and stable gel structure than other pH. The composite gel formed at pH 7.0 was accordingly employed to encapsulate vitamin D3. Results exhibited that the encapsulation of composite gel of whey protein isolate and lotus root amylopectin could enhance the storage stability of vitamin D3 and protect vitamin D3 from photochemical degradation. Moreover, this encapsulation could control the release of vitamin D3 in simulated intestinal fluid. Animal experiments exhibited that the bioavailability was significantly increased after vitamin D3 was encapsulated by the composite gel. This work indicated that the whey protein isolate-lotus root amylopectin gel is a good delivery system to improve the stability and bioavailability of vitamin D3.

Growth factor release from amylopectin hydrogel based on copper coordination.

This paper describes a biodegradable hydrogel matrix releasing basic fibroblast growth factor (bFGF) on the basis of protein metal coordination with the protein drug. The biodegradable hydrogel was prepared from amylopectin by its crosslinking with ethylene glycol diglycidyl ether, followed by introduction of diethylenetriaminepentaacetic acid (DTPA) residues for copper chelation. When bFGF was incorporated into the DTPA-introduced amylopectin hydrogel after chelation with Cu2+, an insignificant amount of bFGF was released from the hydrogel in buffered solution, in contrast to that without Cu2+ chelation. An increased ionic strength in the solution did not affect the bFGF release, indicating the occurrence of coordinate bonding of bFGF to the DTPA-introduced hydrogel through Cu2+ chelation. An implantation study with 125I-labeled amylopectin hydrogels demonstrated that they underwent degradation in the back subcutis of mice. Cu2+ chelation of hydrogels enabled bFGF to remain in the mouse back for a long time period, irrespective of DTPA introduction. However, DTPA residues were necessary to induce significant neovascularization by the Cu2+-chelating hydrogels incorporating bFGF. The DTPA-introduced amylopectin prevented Cu2+-induced deactivation of bFGF, again in marked contrast to DTPA-free amylopectin. It was concluded that biologically active bFGF could be incorporated to DTPA-introduced amylopectin through Cu2+ chelation in a stabilized state and was released as a result of hydrogel biodegradation, resulting in prolonged neovascularization.

Polysaccharide-coated liposomal amphotericin B for the treatment of murine pulmonary candidiasis.

Amylopectin-coated liposomal amphotericin B was investigated in a murine model of pulmonary candidiasis. The LD50 of amylopectin-coated liposomal amphotericin B in normal mice was more than 10.0 mg/kg, and that of conventional amphotericin B was 1.2 mg/kg. Amylopectin-coated liposomes showed twice the concentration in the lungs of conventional liposomes. Candida albicans was inoculated intratracheally into BALB/C mice. Twenty-four hours later, the number of Candida in the lungs of mice treated with amylopectin-coated liposomes was less than in those treated with conventional liposomes, and amylopectin-coated liposomes improved the survival rate of inoculated mice. Coating liposomes with amylopectin aids the targeting of amphotericin B to the lungs.

Development of insulin resistance in the rat is dependent on the rate of glucose absorption from the diet.

The effect of long-term consumption of diets of different carbohydrate composition was investigated be feeding rats for up to 52 wk on diets in which the carbohydrate was either glucose, amylose or amylopectin. A glucose-based diet was included to examine the relationship between the rate of carbohydrate absorption from the diet and the development of insulin resistance. Insulin sensitivity was assessed by subjecting animals to an intravenous glucose tolerance test (IVGTT). Amylopectin-fed animals became progressively insulin resistant from 12 to 26 wk of feeding. The area under the plasma insulin curves in response to a glucose load (IVGTT) for these animals rose progressively from 15.1 +/- 2.5 nmol/L.30 min at 8 wk to 45.8 +/- 3.5 nmol/L.30 min (P < 0.001) at 26 wk of feeding. Amylose-fed animals did not exhibit insulin resistance until 26 wk of feeding when insulin secretion in response to a glucose load was 28.3 +/- 0.9 vs. 14.6 +/- 3.2 nmol/L.30 min at 16 wk of feeding (P < 0.005). Glucose-fed animals displayed insulin resistance after only 8 wk of feeding. At this time, the area under their plasma insulin curves was almost double that for amylose- or amylopectin-fed animals (P < 0.001). We conclude that long-term consumption of a diet in which available carbohydrate is rapidly absorbed causes insulin resistance in rats. The more rapidly glucose is absorbed from the diet, the faster the insulin resistance develops.