Multilayer nanoparticles for sustained delivery of exenatide to treat type 2 diabetes mellitus

Kim, Jae Yeon; Lee, Hwanbum; Oh, Keun Sang; Kweon, Seho; Jeon, Ok Cheol; Byun, Youngro; Kim, Kwangmeyung; Kwon, Ick Chan; Kim, Sang Yoon; Yuk, Soon Hong

doi:10.1016/j.biomaterials.2013.07.040

Cited by 33 publications

(18 citation statements)

References 31 publications

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“…5f ), and measurement of mechanical strength using a tensile compression apparatus indicated that integration of mineralized particles significantly increased the failure force of blank alginate MNs by 1.93 fold (from 0.15 to 0.29 N per needle) (Fig. 5g ), owing to the crosslinking effect of mineralized particles, which reinforced the stability of the MN at the cost of reducing the extensibility of the polymer network 46 . Importantly, this range of failure force (≥16 N per array) 52 indicated sufficient MN stiffness and strength to facilitate skin penetration without deformation 53 .…”

Section: Resultsmentioning

confidence: 93%

“…To realize less invasive (more facile) administration, the dual mineralized particles were incorporated into the indissoluble MN-array patch. Interestingly, the incorporation of mineralized particles significantly improved mechanical strength and skin penetration capability of the patch but had little influence on the diffusion of small molecules from porous gel network 46 , demonstrating a sustained transdermal administration. Compared to traditional ID injection, MN-array patch treatment induced a milder inflammatory reaction due to less invasiveness of the patch approach, and after treatment, the patch could be easily removed, suggesting a disposable manner.…”

Section: Discussionmentioning

confidence: 99%

“…To realize facile administration, the dual mineralized particles are loaded onto an alginate-based MN-array patch for convenient and non-invasive drug delivery 28 – 30 . Importantly, the integration of mineralized particles can significantly improve the mechanical strength of MN for skin penetration by crosslinking effect to reinforce the alginate gel at the cost of reducing the extensibility of the polymeric networks 46 . In this way, a patch-based delivery system providing long-term glucose responsiveness and on-demand Ex4 release is constructed, which may serve as a reliable and effective candidate for glucose regulation in T2D.…”

Section: Introductionmentioning

confidence: 99%

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Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy

et al. 2017

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The delivery of therapeutic peptides for diabetes therapy is compromised by short half-lives of drugs with the consequent need for multiple daily injections that reduce patient compliance and increase treatment cost. In this study, we demonstrate a smart exendin-4 (Ex4) delivery device based on microneedle (MN)-array patches integrated with dual mineralized particles separately containing Ex4 and glucose oxidase (GOx). The dual mineralized particle-based system can specifically release Ex4 while immobilizing GOx as a result of the differential response to the microenvironment induced by biological stimuli. In this manner, the system enables glucose-responsive and closed-loop release to significantly improve Ex4 therapeutic performance. Moreover, integration of mineralized particles can enhance the mechanical strength of alginate-based MN by crosslinking to facilitate skin penetration, thus supporting painless and non-invasive transdermal administration. We believe this smart glucose-responsive Ex4 delivery holds great promise for type 2 diabetes therapy by providing safe, long-term, and on-demand Ex4 therapy.

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Section: Resultsmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy

et al. 2017

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“…Recently, the multi-scale drug delivery system with tiny nanoparticles as ‘seed’ (gold particle, silica particle, or polymer nanoparticles such as pluronic, polystyrene, or PLGA (Yuk et al., 2011 ; Kim et al., 2013 ; Oh et al., 2013 )) in the aqueous phase of larger liposomes/vesicles or inside a matrix nanoparticles (Wong et al., 2011 ), has gained significant attention, which could ‘bomb’ upon tumor microenvironment to meet different requirements from circulation and tumor penetration by size adaptation (Sunoqrot et al., 2014 ). Apart from the smart adapting function, this composite drug delivery system was hypothesized to improve drug retention by providing double barriers for drug release (Yuk et al., 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy

Zhang

et al. 2018

Drug Delivery

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To improve drug retention in carriers for amphiphilic asulacrine (ASL), a novel active loading method using micelle gradient was developed to fabricate the ASL-loaded multiseed liposomes (ASL-ML). The empty ML were prepared by hydrating a thin film with empty micelles. Then the micelles in liposomal compartment acting as ‘micelle pool’ drove the drug to be loaded after the outer micelles were removed. Some reasoning studies including critical micelle concentration (CMC) determination, influencing factors tests on entrapment efficiency (EE), structure visualization, and drug release were carried out to explore the mechanism of active loading, ASL location, and the structure of ASL-ML. Comparisons were made between pre-loading and active loading method. Finally, the extended drug retention capacity of ML was evaluated through pharmacokinetic, drug tissue irritancy, and in vivo anti-tumor activity studies. Comprehensive results from fluorescent and transmission electron microscope (TEM) observation, encapsulation efficiency (EE) comparison, and release studies demonstrated the formation of ML-shell structure for ASL-ML without inter-carrier fusion. The location of drug mainly in inner micelles as well as the superiority of post-loading to the pre-loading method , in which drug in micelles shifted onto the bilayer membrane was an additional positive of this delivery system. It was observed that the drug amphiphilicity and interaction of micelles with drug were the two prerequisites for this active loading method. The extended retention capacity of ML has been verified through the prolonged half-life, reduced paw-lick responses in rats, and enhanced tumor inhibition in model mice. In conclusion, ASL-ML prepared by active loading method can effectively load drug into micelles with expected structure and improve drug retention.

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“…Kim et al (2013) DOI: 10.3109/10717544.2014 proved as a carrier of choice for the drug accumulation at the desired site of action. Several formulation strategies, namely thin film hydration and membrane dialyzing method (Huang & Wang, 2006), two-step double emulsification (Pardakhty et al, 2007), modified reverse phase evaporation (Pardakhty et al, 2007;Misra et al, 2009), etc., are made to develop such liposomes using a variety of polymers.…”

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confidence: 99%

Novel drug delivery system: an immense hope for diabetics

et al. 2014

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Context: Existing medication systems for the treatment of diabetes mellitus (DM) are inconvenient and troublesome for effective and safe delivery of drugs to the specific site. Therefore, investigations are desired to deliver antidiabetics using novel delivery approaches followed by their commercialization. Objective: The present review aims to provide a compilation on the latest development in the field of novel drug delivery systems (NDDSs) for antidiabetics with special emphasis on particulate, vesicular and miscellaneous systems. Methods: Review of literature (restricted to English language only) was done using electronic databases like Pubmed Õ and Scirus, i.e. published during [2005][2006][2007][2008][2009][2010][2011][2012][2013]. The CIMS/MIMS India Medical Drug Information eBook was used regarding available marketed formulation of antidiabetic drugs. Keywords used were ''nanoparticle'', ''microparticle'', ''liposomes'', ''niosomes'', ''transdermal systems'', ''insulin'', ''antidiabetic drugs'' and ''novel drug delivery systems''. Single inclusion was made for one article. If in vivo study was not done then article was seldom included in the manuscript. Results: The curiosity to develop NDDSs of antidiabetic drugs with special attention to the nanoparticulate system followed by microparticulate and lipid-based system is found to emerge gradually to overcome the problems associated with the conventional dosage forms and to win the confidence of end users towards the higher acceptability. Conclusion: In the current scientific panorama when the area of novel drug delivery system has been recognized for its palpable benefits, unique potential of providing physical stability, sustained and site-specific drug delivery for a scheduled period of time can open new vistas for precise, safe and quality treatment of DM.

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Multilayer nanoparticles for sustained delivery of exenatide to treat type 2 diabetes mellitus

Cited by 33 publications

References 31 publications

Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy

Microneedle-array patches loaded with dual mineralized protein/peptide particles for type 2 diabetes therapy

Multiseed liposomal drug delivery system using micelle gradient as driving force to improve amphiphilic drug retention and its anti-tumor efficacy

Novel drug delivery system: an immense hope for diabetics

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