In vitro release behavior and stability of insulin in complexation hydrogels as oral drug delivery carriers

Kim, Bumsang; Peppas, Nicholas A.

doi:10.1016/s0378-5173(03)00378-8

Cited by 123 publications

(67 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Due to the presence of chemical or physical crosslinking, they can make conventional change of volume in response with different pH values, namely swelling or deswelling in solvents of different pH values (Gupta et al, 2002;Kim & Peppas, 2003;Ranjha et al, 2008;Nguyen et al, 2009;Wang et al, 2010a). Therefore, they have more potential applications in drug delivery systems, especially oral drug delivery systems owning to the particularity of the physiological structure of the digestive tract (the pH in the upper gastrointestinal tract is relatively low, while in the lower gastrointestinal tract is higher) (Peppas et al, 2004;Sande, 2005;Guo & Gao, 2007;Wong, 2010;Chaturvedi et al, 2012;Yang et al, 2012).…”

Section: Introductionmentioning

confidence: 99%

Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel

Dong

You

et al. 2014

Drug Delivery

View full text Add to dashboard Cite

, then mixing them together to prepare hydrogel through the heat-initiated free radical polymerization method. Differential scanning calorimetry and X-ray diffraction methods were used to verify whether dexamethasone was loaded into hydrogels. In vitro drug release behavior and in vivo pharmacokinetic study were also investigated in detail.Results: Dexamethasone was successfully loaded into hydrogel, and its loading capacity was improved (5 mg/g). Both the in vitro release study and the in vivo pharmacokinetic study showed the good colon-targeting character of the pH-sensitive P(LE-IA-MEG) hydrogel (T max ¼ 1.0 h, C max ¼ 2.16 mg/ml of dexamethasone; T max ¼ 3.9 h, C max ¼ 0.43 mg/ml of dexamethasone hydrogel). Discussion: Dexamethasone could be targeted to the colon site by P(LE-IA-MEG) hydrogel, thereby improving its therapeutic effect and reduce its side effects. Conclusion: P(LE-IA-MEG) hydrogel might have great potential application in colon-targeted drug delivery systems. KeywordsDexamethasone, drug-loading, in vitro drug release study, in vivo pharmacokinetic study, pH-sensitive History

show abstract

Section: Introductionmentioning

confidence: 99%

Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel

Dong

You

et al. 2014

Drug Delivery

View full text Add to dashboard Cite

show abstract

“…The amount of insulin contained in each batch of the formulations was determined by the HPLC method (Builders et al, 2008b). The drug loading efficiency was then determined by evaluating with Equation 2 (Kim & Peppas, 2003;Cui et al, 2006;Sarmento et al, 2007).…”

Section: Insulin Loading Efficiencymentioning

confidence: 99%

“…Blood glucose reduction occurred within 30 min of oral administration in some samples. This could be attributed to such factors as early gastric emptying of the drug from the stomach into the small intestine and the effective mucoadhesiveness of the polymer matrix (Eudragit Õ RL 100) that was efficient in adhering the microspheres to the gastric mucosa and protecting the insulin from degradation which is one of the major drawbacks in oral insulin delivery (Beals & Kovach, 1997;Kisel et al, 2001;Owens, 2002;Giriraj & Giriraj, 2003;Gowthamarajan & Kulkarni, 2003;Kim & Peppas, 2003;Whitehead et al, 2004;Cui et al, 2006;Morishita & Peppas, 2006;Sarmento et al, 2007;Pamnani, 2008). It was helpful to protect insulin activity against the enzymatic attack in harsh environment of stomach and intestine.…”

Section: Blood Glucose Reducing Efficiencymentioning

confidence: 99%

“…Insulin is administered parenterally by subcutaneous injection (Beals & Kovach, 1997), which results in low level of compliance due to pain as well as complications due to multiple jabs, hence the need for an alternative less invasive but effective method of insulin administration (Gowthamarajan & Kulkarni, 2003). The oral route is considered to be the most convenient, acceptable and desired route of drug delivery which will help eliminate the pain caused by injection, psychological barrier associated with multiple daily injection and possible infections (Kisel et al, 2001;Kim & Peppas, 2003;Whitehead et al, 2004;Cui et al, 2006;Sarmento et al, 2007). Oral delivery of insulin as a non-invasive therapy for diabetes mellitus is still a challenge to the drug delivery technology, due to low oral bioavailability, lack of lipophility, poor permeability across intestinal epithelium because of insulin high molecular weight as well as digestion by proteolytic enzymes in the luminal cavity (Tozaki, 2001; Gowthamarajan & Kulkarni, 2003;Tiyaboonchai, 2003;Krauland et al, 2004;Li & Deng, 2004;Nakamura et al, 2004;Toorisaka et al, 2005;Sajeesh & Sharma, 2006;Sarmento, 2006;Tuesca & Lowman, 2006;Lin, 2007;Simon, 2007).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres

et al. 2014

View full text Add to dashboard Cite

Effective oral insulin delivery has remained a challenge to the pharmaceutical industry. This study was designed to evaluate the effect of magnesium stearate on the properties of insulin-loaded Eudragit Õ RL 100 entrapped mucoadhesive microspheres. Microspheres containing Eudragit Õ RL 100, insulin, and varying concentrations of magnesium stearate (agglomeration-preventing agent) were prepared by emulsification-coacervation method and characterized with respect to differential scanning calorimetry (DSC), morphology, particle size, loading efficiency, mucoadhesive and micromeritics properties. The in vitro release of insulin from the microspheres was performed in simulated intestinal fluid (SIF, pH 7.2) while the in vivo hypoglycemic effect was investigated by monitoring the plasma glucose level of the alloxaninduced diabetic rats after oral administration. Stable, spherical, brownish, mucoadhesive, discrete and free flowing insulin-loaded microspheres were formed. While the average particle size and mucoadhesiveness of the microspheres increased with an increase in the proportion of magnesium stearate, loading efficiency generally decreased. After 12 h, microspheres prepared with Eudragit Õ RL 100: magnesium stearate ratios of 15:1, 15:2, 15:3 and 15:4 released 68.20 ± 1.57, 79.40 ± 1.52, 76.60 ± 1.93 and 70.00 ± 1.00 (%) of insulin, respectively. Reduction in the blood glucose level for the subcutaneously (sc) administered insulin was significantly (p 0.05) higher than for most of the formulations. However, the blood glucose reduction effect produced by the orally administered insulin-loaded microspheres prepared with four parts of magnesium stearate and fifteen parts of Eudragit Õ RL 100 after 12 h was equal to that produced by subcutaneously administered insulin solution. The results of this study can suggest that this carrier system could be an alternative for the delivery of insulin.

show abstract

“…It would be advantageous to investigate formulations prepared with a biodegradable matrix. Since insulin and amphiphilic copolymers both possess hydrophobic and hydrophilic segments, it is expected that they are mutually compatible and may be advantageous to the efficacy of the resultant drug formulations [12].…”

Section: Introductionmentioning

confidence: 99%

Self-assembled nanomicelles using PLGA–PEG amphiphilic block copolymer for insulin delivery: a physicochemical investigation and determination of CMC values

Ashjari

Khoee

Mahdavian

et al. 2012

J Mater Sci: Mater Med

View full text Add to dashboard Cite

Self-assembled nanomicelles can be used as synthetic biomaterials and colloidal carriers for poorly water-soluble drug delivery systems. Some of these micellar systems have been introduced in clinical trials and showed hopeful results relating to their therapeutic index in patients. Biodegradable nanomicelle was prepared from self-assembling amphiphilic block copolymer composed of poly(DL-lactic-co-glycolic acid) (PLGA) as a core and polyethylene glycol (PEG) as a corona. The PLGA-PEG block copolymer was first synthesized and characterized by FTIR, (1)H NMR, GPC and inherent viscosity measurements. The nanomicelle formed by PLGA-PEG block copolymer in the aqueous solution was characterized by dynamic light scattering, zeta potential, scanning electron microscopy (SEM) and fluorescence excitation and emission spectra of pyrene probe. The critical micelle concentration of obtained nanomicelle was about 0.006 mg/mL, with the size of about 160 nm and the zeta potential of -29 mV. Insulin-loaded PLGA-PEG nanomicelles were prepared by modified dialysis method and the physicochemical parameters of the micelles such as drug content, entrapment efficiency and in vitro drug release were characterized. The results showed that insulin was entrapped into PLGA-PEG nanomicelles with drug loading of 3.9 wt% and entrapment efficiency of 55 wt%. The nanomicelles containing insulin exhibited a controlled release profile. These observations suggested that the PLGA-PEG block copolymers nanomicelles have been prepared by a new synthetic route are potent nanocarrier for poorly water-soluble drugs as insulin.

show abstract

In vitro release behavior and stability of insulin in complexation hydrogels as oral drug delivery carriers

Cited by 123 publications

References 33 publications

Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel

Assessment of the drug loading, in vitro and in vivo release behavior of novel pH-sensitive hydrogel

Influence of magnesium stearate on the physicochemical and pharmacodynamic characteristics of insulin-loaded Eudragit entrapped mucoadhesive microspheres

Self-assembled nanomicelles using PLGA–PEG amphiphilic block copolymer for insulin delivery: a physicochemical investigation and determination of CMC values

Contact Info

Product

Resources

About