A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin

Li, Lei; Jiang, Guohua; Yang, Yuedong; Liu, Depeng; Chen, Hua; Liu, Yongkun; Huang, Qin; Tong, Zaizai; Yao, Juming; Kong, Xiangdong

doi:10.1016/j.msec.2016.06.059

Cited by 71 publications

(39 citation statements)

References 48 publications

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“…These morphological properties have been connected with water exchange and swelling of hydrogels. Swelling characteristics of hydrogels are essential for material transfer when applied to insulin carriers [ 56 ].…”

Section: Resultsmentioning

confidence: 99%

Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

Nur

Vasiljevic

2018

Materials

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Nanoparticles or microparticles created by physical complexation between two polyelectrolytes may have a prospective use as an excipient for oral insulin administration. Natural polymers such as tragacanth, alginate, dextran, pullulan, hyaluronic acid, gelatin and chitosan can be potential candidates for this purpose. In this research, insulin particles were prepared by the inclusion of insulin into a tragacanth hydrogel. The effect of the pH and concentration relationship involving polyelectrolytes offering individual particle size and zeta potential was assessed by zetasizer and scanning electron microscopy (SEM). Insulin–tragacanth interactions at varying pH (3.7, 4.3, 4.6, or 6), and concentration (0.1%, 0.5%, or 1% w/w) were evaluated by differential scanning calorimetry (DSC) and ATR Fourier transform infrared (ATR-FTIR) analysis. Individual and smaller particles, approximately 800 nm, were acquired at pH 4.6 with 0.5% of tragacanth. The acid gelation test indicated that insulin could be entrapped in the physical hydrogel of tragacanth. DSC thermograms of insulin–tragacanth showed shifts on the same unloaded tragacanth peaks and suggested polyelectrolyte–protein interactions at a pH close to 4.3–4.6. FTIR spectra of tragacanth–insulin complexes exhibited amide absorption bands featuring in the protein spectra and revealed the creation of a new chemical substance.

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Section: Resultsmentioning

confidence: 99%

Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

Nur

Vasiljevic

2018

Materials

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“…After injecting the mice with the NPs, the released insulin can been used to determine the relative bioavailability [46,47]. Lei et al [48] manufactured a composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin and found the glucose-responsive nanocarriers can significantly prolong the time of insulin in the serum. In addition, Depeng et al…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Phenylboronic acid-diol crosslinked 6-O-vinylazeloyl-d-galactose nanocarriers for insulin delivery

Bremner

et al. 2017

Materials Science and Engineering: C

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A new block polymer named poly 3-acrylamidophenylboronic acid-b-6-O-vinylazeloyl-d-galactose (p(AAPBA-b-OVZG)) was prepared using 3-acrylamidophenylboronic acid (AAPBA) and 6-O-vinylazeloyl-d-galactose (OVZG) via a two-step procedure involving S-1-dodecyl-S-(α', α'-dimethyl-α″-acetic acid) trithiocarbonate (DDATC) as chain transfer agent, 2,2-azobisisobutyronitrile (AIBN) as initiator and dimethyl formamide (DMF) as solvent. The structures of the polymer were examined by Fourier transform infrared spectroscopy (FT-IR) and H NMR and the thermal stability was determined by thermal gravimetric analysis (TG/DTG). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were utilized to evaluate the morphology and properties of the p(AAPBA-b-OVZG) nanoparticles. The cell toxicity, animal toxicity and therapeutic efficacy were also investigated. The results indicate the p(AAPBA-b-OVZG) was successfully synthesized and had excellent thermal stability. Moreover, the p(AAPBA-b-OVZG) nanoparticles were submicron in size and glucose-sensitive in phosphate-buffered saline (PBS). In addition, insulin as a model drug had a high encapsulation efficiency and loading capacity and the release of insulin was increased at higher glucose levels. Furthermore, the nanoparticles showed a low-toxicity in cell and animal studies and they were effective at decreasing blood glucose levels of mice over 96h. These p(AAPBA-b-OVZG) nanoparticles show promise for applications in diabetes treatment using insulin or other hypoglycemic proteins.

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“…Hydroxyethyl methacrylate nanogel via emulsion polymerization was developed for the oral delivery of insulin with improved bioavailability that controlled blood glucose levels for up to 12 hours (Wang et al, 2018). Insulin-loaded glucose responsive nanocarriers dispersed in hyaluronic acid hydrogel, offered better protection (almost 50% more protective than without hyaluronic acid gel nanocarriers) from harsh gastric environment in vivo in rats (Li et al, 2016).…”

Section: Hydrogelsmentioning

confidence: 99%

Oral Drug Delivery Technologies—A Decade of Developments

Kaur

Arora

Kumar

2019

J Pharmacol Exp Ther

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Advanced drug delivery technologies, in general, enable drug reformulation and administration routes, together contributing to life-cycle management and allowing the innovator to maintain the product monopoly. Over the years, there has been a steady shift from mere life-cycle management to drug repurposingapplying delivery technologies to tackle solubility and permeability issues in early stages or safety and efficacy issues in the late stages of drug discovery processes. While the drug and the disease in question primarily drive the choice of route of administration, the oral route, for its compliance and safety attributes, is the most preferred route, particularly when it comes to chronic conditions, including pain, which is not considered a disease but a symptom of a primary cause. Therefore, the attempt of this review is to take a stock of the advances in oral delivery technologies that are applicable for injectable to oral transformation, improve risk-benefit profiles of existing orals, and apply them in the early discovery program to minimize the drug attrition rates.

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A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin

Cited by 71 publications

References 48 publications

Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

Insulin Inclusion into a Tragacanth Hydrogel: An Oral Delivery System for Insulin

Phenylboronic acid-diol crosslinked 6-O-vinylazeloyl-d-galactose nanocarriers for insulin delivery

Oral Drug Delivery Technologies—A Decade of Developments

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