pH-sensitive poly(lactide-co-glycolide) nanoparticle composite microcapsules for oral delivery of insulin

Abstract

This study proposes a new concept of pH-sensitive poly(lactide-co-glycolide) (PLGA) nanoparticle composite microcapsules for oral delivery of insulin. Firstly, insulin–sodium oleate complex was prepared by the hydrophobic ion pairing method and then encapsulated into PLGA nanoparticles by the emulsion solvent diffusion method. In order to reduce the burst release of insulin from PLGA nanoparticles and deliver insulin to specific gastrointestinal regions, hence to enhance bioavailability of insulin, the PLGA nanoparticles were further encapsulated into Eudragit ® FS 30D to prepare PLGA nanoparticle composite microcapsules by organic spray-drying method. The preparation was evaluated in vitro and in vivo, and the absorption mechanism was discussed. The in vitro drug release studies revealed that the drug release was pH dependent, and the in vivo results demonstrated that the formulation of PLGA nanoparticle composite microcapsules was an effective candidate for oral insulin delivery.

Polymer degradation and drug delivery in PLGA‐based drug–polymer applications: A review of experiments and theories

“…To overcome such drawbacks, versatile approaches have been explored to functionalize bare PLGA materials, generally including conjugation with cell‐targeting ligands, polyion complexation, lipid‐ or surfactant‐coating, and surface modification by PEG . Because PLGA has been widely used in controlled release systems, especially in parenteral and implantation applications, stimulated drug delivery systems based on PLGA have been developed including light‐triggered drug delivery, electro‐responsive systems, and pH‐sensitive systems . Also, a “random” copolymerization technique has been applied to control the dispersity of PLGA copolymers for stimulated drug release …”

“…146,147 Because PLGA has been widely used in controlled release systems, especially in parenteral and implantation applications, [146][147][148] stimulated drug delivery systems based on PLGA have been developed including light-triggered drug delivery, 149,150 electro-responsive systems, 151 and pH-sensitive systems. [152][153][154][155] Also, a "random" copolymerization technique has been applied to control the dispersity of PLGA copolymers for stimulated drug release. 105,156,157 On the other hand, sustained delivery forms are sometimes highly desirable to avoid concentration peak and valley in human body and enhance patient compliance.…”

Strategies for the enhanced intracellular delivery of nanomaterials

“…Thus, modifying the surface of nanomaterials with particular ligands is one way to improve their cellular uptake and endosomal escape [39]. Table 2 summarizes receptors targeted in this approach, including CD31, integrin b3 and transferrin [122], TLR2, TLR3 and TLR9 [123], avb3 integrin [119], transferrin [124], EGFR [125], CD44 [126], IGFR [127],FcRn [128], CD163 [129], biotin [130], folate [131], and vitamin B 12 [132].…”

A composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin

“…[1] Insulin is a peptide that consisted of 51 amino acids, and it has the ability to control the blood glucose level by facilitating the uptake of glucose. [2] Despite the significant developments in insulin therapy over the past few decades, subcutaneous injection of insulin remains the preferred approach for the treatment of insulin-requiring diabetic patients due to ease of administration. Despite their widespread use, such injections must pass through the skin or mucosal barrier, resulting in dermal trauma and pain.…”

“…Furthermore, it also causes inconvenient, resulting in poor patient compliance. [2,3] Development of an oral delivery strategy for insulin therapeutics has draw much attention to both patients and the protein therapeutics industry. It not only alleviates the pain caused by injections, but can also mimic the physiological fate of insulin and may provide a better glucose homeostasis.…”