Microfabricated microporous membranes reduce the host immune response and prolong the functional lifetime of a closed-loop insulin delivery implant in a type 1 diabetic rat model

Importance of integrating nanotechnology with pharmacology and physiology for innovative drug delivery and therapy – an illustration with firsthand examples

“…Recent advances in nanomaterials offer new opportunities for developing next-generation closed-loop insulin delivery systems that better mimic the endocrinological secretion of insulin [9] . Our laboratory introduced pH-responsive hydrogel NPs to replicate the rapid and dynamic insulin release at physiologically relevant time scales [168][169][170][171][172][173][174] . The hydrogel NPs, embedded in a pH-insensitive polymer membrane ( Figure 7C), undergo a volume-phase transition from a swollen state at physiological pH to a collapsed state at acidic pH below their pK a [175,176] .…”

“…When combined with glucose oxidase (GOx), the pH-responsive nanogels shrink in response to decreased local pH due to the production of gluconic acid from the catalyzed glucose oxidation. The glucose-responsive volume change of the nanogels regulates the permeability of the composite membrane and thus controls the rate of insulin release from the reservoirs ( Figure 7D) [168][169][170][171][172][173][174] .…”

“…Although catalase is incorporated in some devices to recover consumed O 2 , it can only convert half of the byproduct H 2 O 2 back to O 2 . To solve this problem, we introduced MDNPs in the composite membrane to continuously catalyze the breakdown of H 2 O 2 to molecular O 2 and water at a one-to-one molar ratio (H 2 O 2 + 2H + -MnO2 ----→ O 2 + 2 H 2 O) ( Figure 7D) [169,172,173] . In this way, the incorporated MDNPs not only reduced the enzyme-damaging H 2 O 2 , a by-product of glucose oxidation, preserving the enzymatic activity of GOx and catalase, but also raised the microdomain pH, avoiding over-acidification at low glucose concentration [172,179] .…”

Synthesis of surfactant-free hydroxypropyl methylcellulose nanogels for controlled release of insulin

“…(Qiang, Zhi-Rong, Tao, Guo-Qiang & Xun, 2012) A controlled and prolonged release system is needed to reduce the injection frequency and increase the compliance of diabetic patient. (Jun et al, 2012;Li et al, 2015;Yi et al, 2015) Sustained release systems which use a variety of different polymers especially nanogels as carrier materials to wrap peptide and protein drugs have become a new field of research. They are aimed at improving the stability of drugs, enhancing oral bioavailability and achieving sustained release of drugs.…”

Dispositivo implantável de EUDRAGIR/PCL-T/ Diclofenaco de sódio: caracterização mecânica, liberação do fármaco e atividade anti-inflamatóriain vivo

“…Many of these systems are in early stages of development, and a number of questions are yet to be answered. [1][2][3][4][5][6][7] The non-steroidal anti-inflammatory drugs (NSAIDs) are among the most commonly consumed medications in the world. They are used to decrease pain and inflammation caused by various diseases, such as in the treatment of arthritis.…”