Microgel encapsulated nanoparticles for glucose-responsive insulin delivery

Volpatti, Lisa R.; Facklam, Amanda; Cortinas, Abel B.; Yu-qi, LU; Matranga, Morgan A.; MacIsaac, Corina; Hill, Michael C.; Langer, Robert; Anderson, Daniel G.

doi:10.1016/j.biomaterials.2020.120458

Cited by 42 publications

(45 citation statements)

References 54 publications

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“…INS is the most important drug against the diabetes mellitus disease which is a chronic condition that affects the everyday life of millions of patients. [ 25 ] Administration of INS to the blood stream is necessary to sustain the proper glucose levels and current research is focusing on its delivery by polymeric nanocarriers with examples from polymeric microgels [ 26 ] and block copolymers. [ 27 ] As there is a lack of reports on interactions of mikto‐arm star polyelectrolytes with biological molecules and especially proteins, he interaction of the two mikto‐arm star copolymers with INS has been studied in aqueous media.…”

Section: Resultsmentioning

confidence: 99%

Star Polyelectrolytes with Mixed Arms of PDMAEMA and POEGMA: Self‐Assembly and Coassembly with Insulin

Vlassi

Papagiannopoulos

Pispas

2022

Macro Chemistry & Physics

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Star copolymers with mixed polyelectrolyte/hydrophilic arms of poly(2-(dimethylamino) ethyl methacrylate) (PDMAEMA) and poly(oligo (ethylene glycol) methyl ether methacrylate) (POEGMA) have been synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization and the arm-first method. The star polyelectrolytes self-assemble in aqueous media in nanostructures of hydrodynamic radius in the order of 50 nm. The quaternized star-QPDMAEMA x -POEGMA y aggregates appear to have a higher surface charge and a looser morphology in comparison to the annealed (weakly charged) star-PDMAEMA x -POEGMA y aggregates. The cationic mikto-arm stars coassemble into complexes with insulin (INS) at neutral pH. In the case of the annealed stars INS appears to bind homogeneously to the fractal-like aggregates. However, in the quenched (strongly charged) stars the protein rather attaches to the periphery of the compact aggregates. Interestingly, the size and mass of the star/INS complexes pass through a maximum as a function of the salt content for high INS contents. This is attributed to the anisotropic charge distribution of INS at pH 7, an effect that is reported only for linear and not for star polyelectrolytes. This work motivates the use of the star-PDMAEMA x -POEGMA y polyelectrolytes for the immobilization and delivery of protein drugs.

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Section: Resultsmentioning

confidence: 99%

Star Polyelectrolytes with Mixed Arms of PDMAEMA and POEGMA: Self‐Assembly and Coassembly with Insulin

Vlassi

Papagiannopoulos

Pispas

2022

Macro Chemistry & Physics

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“…Alginate was cross-linked with divalent cations to form the microgel platform, and the nanoparticles were synthesized using acetylateddextran, glucose oxidase, and catalase before loading insulin. The alginate-based microgel demonstrated the ability to maintain glucose-responsive insulin release in preclinical testing with homeostatic blood glucose levels achieved using two doses over a period of 21 days in vivo [45].…”

Section: The Use Of Microgels For the Controlled Delivery Of Insulinmentioning

confidence: 99%

Advanced Hydrogels for the Controlled Delivery of Insulin

2021

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Insulin is a peptide hormone that is key to regulating physiological glucose levels. Its molecular size and susceptibility to conformational change under physiological pH make it challenging to orally administer insulin in diabetes. The most effective route for insulin delivery remains daily injection. Unfortunately, this results in poor patient compliance and increasing the risk of micro- and macro-vascular complications and thus rising morbidity and mortality rates in diabetics. The use of 3D hydrogels has been used with much interest for various biomedical applications. Hydrogels can mimic the extracellular matrix (ECM) and retain large quantities of water with tunable properties, which renders them suitable for administering a wide range of sensitive therapeutics. Several studies have demonstrated the fixation of insulin within the structural mesh of hydrogels as a bio-scaffold for the controlled delivery of insulin. This review provides a concise incursion into recent developments for the safe and effective controlled delivery of insulin using advanced hydrogel platforms with a special focus on sustained release injectable formulations. Various hydrogel platforms in terms of their methods of synthesis, properties, and unique features such as stimuli responsiveness for the treatment of Type 1 diabetes mellitus are critically appraised. Key criteria for classifying hydrogels are also outlined together with future trends in the field.

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“…The glucose-responsive delivery system was developed by encapsulating glucose-responsive, acetylated-dextran microparticles in porous alginate microgels to improve glycemic control by releasing insulin into the blood, thereby detecting an elevation in the blood glucose levels. 94 Moreover, catechin is a natural molecule that possesses antidiabetic activity, but a significant disadvantage of it is that it causes obesity. To overcome this problem, scientists have encapsulated catechin into Eudragit RS100 microparticles.…”

Section: Improving Drug Dissolutionmentioning

confidence: 99%

An Overview of Microparticulate Drug Delivery System and its Extensive Therapeutic Applications in Diabetes

Rafiee

Rasool

2021

Adv Pharm Bull

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Microparticulate drug delivery system (MDDS) has attained much consideration in the modern era due to its effectiveness in overcoming traditional treatment problems. Microparticles are spherical particles of a diameter ranging from 10 μm to 1000 μm. Microparticles can encapsulate both water-soluble and insoluble compounds. MDDS proved their efficacy in improving drugs bioavailability, stability, targeting, and controlling their release patterns. Microparticles also offer comfort, easy administration, and improvement in patient compliance by reducing drugs toxicity and dosage frequency. This review elucidates the fabrication techniques, drug release, and therapeutic application of MDDS. Further details concerning the therapeutic applications of antidiabetic drugs-loaded microparticles were also reviewed, including controlling drugs release by gastroretention, improving drugs dissolution, reducing side effects, localizing drugs to the site of disease, improving insulin stability, natural products loaded with microparticles, sustained drug release, mucosal delivery, and administration routes. Additionally, the current situation and future prospects in developing microparticles loaded with antidiabetic drugs were discussed.

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Microgel encapsulated nanoparticles for glucose-responsive insulin delivery

Cited by 42 publications

References 54 publications

Star Polyelectrolytes with Mixed Arms of PDMAEMA and POEGMA: Self‐Assembly and Coassembly with Insulin

Star Polyelectrolytes with Mixed Arms of PDMAEMA and POEGMA: Self‐Assembly and Coassembly with Insulin

Advanced Hydrogels for the Controlled Delivery of Insulin

An Overview of Microparticulate Drug Delivery System and its Extensive Therapeutic Applications in Diabetes

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