Insulin-loaded hydroxyapatite combined with macrophage activity to deliver insulin for diabetes mellitus

Shyong, Yen Jye; Tsai, Chin‐Feng; Lin, Rui Feng; Soung, Hung Sheng; Hsieh, Hui Chen; Hsueh, Yu Sheng; Chang, Kuo-Song; Lin, Feng Huei

doi:10.1039/c4tb01639d

Cited by 22 publications

(10 citation statements)

References 37 publications

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“…A weight loss at 256°C in thermograms of the insulin loaded hydrogel was associated with the temperature of insulin decomposition (Figure 2b). Similar behavior was reported by Yen-Jye Shyong et al 23 HPLC results for the optimized hydrogel shows that the amount of unloaded insulin in loading medium is 14% of the initial value, which confirm that 86% of insulin was loaded into the hydrogels (Figure 3). The surface morphology of the unloaded and insulin loaded hydrogel was investigated by SEM and the micrographs shows that the synthesized hydrogel has a good porosity (Figure 4a), whereas the pores in insulin loaded hydrogel were fully occupied (Figure 4b).…”

Section: Resultssupporting

confidence: 91%

Thermodynamic Studies of Insulin Loading into a Glucose Responsive Hydrogel Based on Chitosan‐polyacrylamide‐polyethylene Glycol

Farahani

Ghasemzadeh

Afraz

2016

J Chinese Chemical Soc

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The insulin therapy constitutes the preferred treatment for Diabetes Mellitus (DM). The traditional insulin therapy, which consists of daily subcutaneous insulin injections to control blood glucose level, is not able to regulate the blood glucose level precisely. In this research, to facilitate the diabetic patient life, an intelligent drug delivery system based on a biodegrable biopolymer to control the insulin release, was designed. In this system, chitosan-polyethylene glycol hydrogel and glucose oxidize play the role of drug carrier and glucose biosensor, respectively. To increase the hydrogel drug loading capacity, hydrogels with different PEG content were synthesized and insulin was loaded by swelling-diffusion method into them. The loaded hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), High performance liquid chromatography (HPLC), and Thermogravimetric analysis (TGA). Finally, the thermodynamic study for insulin loading process was performed to investigate the stability of the drug in the system.

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Section: Resultssupporting

confidence: 91%

Thermodynamic Studies of Insulin Loading into a Glucose Responsive Hydrogel Based on Chitosan‐polyacrylamide‐polyethylene Glycol

Farahani

Ghasemzadeh

Afraz

2016

J Chinese Chemical Soc

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“…As an alternative to CD measurement, with studies conducted by numerous researchers to prove viability of proteins (18)(19)(20)(21)(22), amide 1 bands were studied in detail, to analyse the α-helix bands using ATR-FTIR, which is the main characteristic of denaturation. This result is highly reliable, and thus confirms the integrity of the proteins after protein release analysis (23). This method analyses deconvolution evaluation of the proteins using a 95% smoothing length and 100 times deconvolution Gamma factor, employing Bessel filter analysis, thus reassuring the integrity of the protein molecules.…”

Section: Determination Of Protein Stability Using Attenuated Total Reflectance-fourier Transform Infrared (Atr-ftir) Spectroscopysupporting

confidence: 65%

“…Histological evaluation of tissue samples from rabbits in the experimental oral microparticles. a Intestinal mucosal crypts confirm normal intestinal mucosa (×10 magnification), b intestinal mucosa which shows normal epithelium (×10 magnification), c fundic portion of the stomach which shows normal fundic glands (×10 magnification), d severe loss of cellularity and necrosis of the islet cells in the islet of Langerhans of rabbits induced with diabetes in the insulin study (×20 magnification) after particle entrapment; however, a significant change was observed in the denatured protein samples (23,31). All proteins obtained significant in vivo responses, as discussed extensively in the following section.…”

Section: Particle Size Distribution Protein-loading Efficiency and In Vitro Evaluation Of The Copolymeric Microparticlesmentioning

confidence: 99%

Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System

et al. 2017

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A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-β) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-β and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-β peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.

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“…The similar mechanism has been used in the other applications in our lab, for instance, antidepression, diabetes mellitus, osteoporosis, etc. [32,33]. Supplementary Figure 2 presents the mechanism of HAP-DPZ, which would be uptake by endocytosis and released by the endosome/lysosome complex.…”

Section: Discussionmentioning

confidence: 99%

Characterization and evaluation of porous hydroxyapatite synthesized by oil-in-water method as carrier of donepezil for the preventive of Alzheimer’s disease by controlled release

Fang

Lin

Yang

et al. 2020

Journal of Asian Ceramic Societies

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Alzheimer's disease (AD) is the most common cause of dementia. Patients are generally to forget taking pills because of memory loss or to skip medication due to side effects; that might stop the medication and affect the results of the treatment. In this study, we combine donepezil with hydroxyapatite (HAP-DPZ) to deliver by intramuscular (IM) injection, which may prevent from patient to skip the daily medication and keep the medicine at a constant level in the blood to achieve a constant release. HAP particles synthesized by using the new oilin-water method, the XRD pattern, and the FTIR spectrum were proved the synthesized of HAP. SEM and DLS showed the particle size of synthesized HAP-DPZ was in the range of 0.9-3 μm, which all in the optimal range for cellular uptake. In the drug release profile, DPZ could be released from HAP-DPZ by endosome/lysosome complex to achieve control releasing. In vitro study, there was no cytotoxicity found in HAP-DPZ. In the animal study, only one injection of HAP-DPZ administration, rats revealed well-focused searching strategies with the longest swimming time and most finding times in the quadrant where the platform was initially after three weeks.

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Insulin-loaded hydroxyapatite combined with macrophage activity to deliver insulin for diabetes mellitus

Abstract: InsHAP is engulfed by macrophages and the lysosome/endosome hybrid is broken down by osmosis, which facilitates delivery of insulin into the bloodstream.

Cited by 22 publications

References 37 publications

Thermodynamic Studies of Insulin Loading into a Glucose Responsive Hydrogel Based on Chitosan‐polyacrylamide‐polyethylene Glycol

Thermodynamic Studies of Insulin Loading into a Glucose Responsive Hydrogel Based on Chitosan‐polyacrylamide‐polyethylene Glycol

Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System

Characterization and evaluation of porous hydroxyapatite synthesized by oil-in-water method as carrier of donepezil for the preventive of Alzheimer’s disease by controlled release

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