Administration of Optimum Sustained-Insulin Release PLGA Microcapsules to Spontaneous Diabetes-Prone BB/WorTky Rats

Takenaga, Mitsuko; Yamaguchi, Yoko; Ogawa, Yasuaki; Kitagawa, Aki; Kawai, Shinichi; Mizushima, Yutaka; Igarashi, Rie; Namae, M; Komeda, Kajuro

doi:10.1080/10717540500315989

Cited by 8 publications

(4 citation statements)

References 17 publications

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“…Because parenteral insulin has such a short half-life in blood (∼4.5 min), frequent insulin injections are required. Various approaches have been tried to extend the in vivo fate of insulin. ,− Insulin-loaded microcapsule transplantation has recently emerged as an attractive alternative to daily insulin injections for patients with type 1 diabetes, and as a promising clinical modality. , …”

Section: Discussionmentioning

confidence: 99%

Insulin-Loaded Microcapsules for In Vivo Delivery

Kim

Hyun

et al. 2009

Mol. Pharmaceutics

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Microencapsulation of insulin has been difficult, due to the high sensitivity of insulin to the harsh conditions that can occur during the microencapsulation process. We have developed a method of preparing insulin-loaded microcapsules by using a monoaxial ultrasonic atomizer to form microdroplets of insulin in aqueous solution surrounded by poly(lactic-co-glycolic acid) (PLGA) solution. Administration of these insulin-loaded microcapsules to type 1 diabetic rats maintained plasma insulin concentrations for 30 days, due to the sustained insulin release properties of the microcapsules. In contrast, plasma insulin concentrations after subcutaneous injection of insulin solution reached near zero levels within 2 days. Insulin solution showed only an immediate pharmacological effect, with no reduction of glycemia after 3 days, whereas insulin-loaded microcapsules maintained blood glucose levels at 100-200 mg/dL for 55 days. Molecular imaging using fluorescein isothiocyanate (FITC)-insulin-loaded microcapsules showed in vivo sustained release of the FITC-insulin in microcapsules. Using insulin-loaded microcapsules, we observed inflammation only immediately after injection, indicating that the rats adapted to long-term insulin release. In conclusion, insulin-loaded microcapsules may reduce nonrepetitive insulin administration and show sustained pharmacological performance.

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Section: Discussionmentioning

confidence: 99%

Insulin-Loaded Microcapsules for In Vivo Delivery

Kim

Hyun

et al. 2009

Mol. Pharmaceutics

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“…After the intraperitoneal administration of streptozotocin a loss of body weight is observed. Body weight changes are currently used as an indicator of the efficacy of the insulin controlled release systems (Takenaga et al, 2002a(Takenaga et al, , 2002bJiang et al, 2003;Kang and Singh, 2005;Takenaga et al, 2006). Figure 6 shows the variation in weight of the different groups of rats.…”

Section: In Vivo Characteristics Of Insulin Loaded Microspheresmentioning

confidence: 98%

“…Therefore, it is possible to study the relationship between in vitro and in vivo characteristics of insulin controlled delivery systems. For these reasons, there are several articles related to the subcutaneous administration of insulin loaded PLGA microparticles and their in vitro and in vivo characteristics (Yamaguchi et al, 2002;Takenaga et al, 2002aTakenaga et al, , 2002bTakenaga et al, , 2004Takenaga et al, , 2006Jiang et al, 2003;Shenoy et al, 2003;Hinds et al, 2005;Kang and Singh, 2005;Kim et al, 2009). Although poly (lactic-co-glycolic acid) (PLGA) is the type of controlled release excipient more frequently used for insulin microencapsulation it is still not clear what is the effect of the PLGA hydrophilia on the pharmacokinetic and pharmacodinamic properties of peptide drugs formulated in this delivery system.…”

Section: Introductionmentioning

confidence: 98%

Effect of PLGA hydrophilia on the drug release and the hypoglucemic activity of different insulin-loaded PLGA microspheres

Presmanes

Miguel

Espada

et al. 2011

Journal of Microencapsulation

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The effects of viscosity and hydrophilic characteristics of different PLGA polymers on the microencapsulation of insulin have been studied in vitro and in vivo after subcutaneous administration to hyperglycemic rats. Hydrophilic PLGA polymers produced a higher burst effect than the hydrophobic ones. Moreover, an incomplete insulin release was observed with the hydrophilic PLGA polymers in comparison with the hydrophobic ones. An explanation for that incomplete release can be the development of polymer-insulin interactions associated to the polymer hydrophilic/hydrophobic character, as detected by DSC analysis. Differences in the release rate of microsphere formulations lead to differences in the hypoglycemic action and the weight of animals. Hydrophobic PLGA was able to prolong the hypoglycemic action up to 4 weeks which is at least double than that obtained with hydrophilic PLGA of a similar viscosity. Comparing insulin microspheres with an immediate release formulation, microspheres can increase insulin relative bioavailability up to four times.

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“…It has been reported that the PLGA microspheres can be successfully used to encapsulate proteins, peptides or drugs for later release in vivo [1][2][3][4][5][6][7][8][9][10][11]. The use of a PLGA matrix to deliver such bioactive molecules has gained popularity due to its favorable biocompatibility and biodegradability [12].…”

Section: Introductionmentioning

confidence: 99%