Development of a Gastric Absorptive, Immediate Responsive, Oral Protein-Loaded Versatile Polymeric Delivery System

Abstract

A multifunctional platform to deliver three diverse proteins of insulin, interferon beta (INF-β) and erythropoietin (EPO), using a novel copolymeric microparticulate system of TMC-PEGDMA-MAA, was synthesised as an intelligent pH-responsive 2-fold gastric and intestinal absorptive system. Physiochemical and physicomechanical studies proved the degree of crystallinity that supported the controlled protein delivery of the microparticulate system. The copolymer was tableted before undertaking in vitro and in vivo analysis. After 2.5 h in simulated gastric fluid (SGF), insulin showed a fractional release of 3.2% in comparison to simulated intestinal fluid (SIF), in which a maximum of 83% of insulin was released. Similarly, INF-β and EPO released 3 and 9.7% in SGF and a maximum of 74 and 81.3% in SIF, respectively. In vivo studies demonstrated a significant decrease in blood glucose by 54.19% within 4 h post-dosing, and the comparator formulation provided 74.6% decrease in blood glucose within the same time period. INF-β peak bioavailable dose in serum was calculated to be 1.3% in comparison to an SC formulation having a peak concentration of 0.9%, demonstrating steady-state release for 24 h. EPO-loaded copolymeric microparticles had a 1.6% peak bioavailable concentration, in comparison to the 6.34% peak concentration after 8 h from the SC comparator formulation.

Synthesis and Evaluation of a Sodium Alginate-4-Aminosalicylic Acid Based Microporous Hydrogel for Potential Viscosupplementation for Joint Injuries and Arthritis-Induced Conditions

“…FTIR and C 13 NMR spectroscopy were undertaken for further confirmation of amide bond formation in the conjugates. In the FTIR spectral analysis, alginate exhibited its characteristic IR bands, as follows: ( Figure 1 a): ν max (cm −1 ) 3302 br (–OH stretch), 2925 w (CH stretch), 1594 s (–CO stretch), 1405 w (C-C bend), 1084 and1025 s br (C–O–C stretch), and 884 cm −1 (C 1 –H β-mannuronate unit) [ 29 , 30 , 31 ]. The FTIR spectrum of amide conjugate in Alg-4-ASA (1:1) was shown in Figure 1 b, which exhibited ν max (cm −1 ) at 3304 s (–OH and/or NH stretch), 2923 m (CH 2 and CH stretch), a band of the carbonyl (CO) stretch for amide (amide I band) at 1693 s cm −1 , 1598 m (–NH, secondary amide II band), and 1243 m (–NH, amide III band) [ 29 , 30 , 31 , 32 ].…”

Sustained in vitro interferon-beta release and in vivo toxicity of PLGA and PEG-PLGA nanoparticles

“…Since very limited number of papers are available in IFN-b drug delivery by nano or microparticles, the comparison with literature data is quite difficult. The most promising results in this aspect were published by Kondiah et al 29 They prepared pH responsive copolymeric trimethyl chitosan-poly(ethylene glycol)-dimethacrylatemethacrylic acid microparticles by free radical suspension polymerisation technique for oral IFN-b controlled delivery. However, for IFN-b, the commercially available and clinically tested products are exclusively intramuscular or subcutaneous formulations.…”

Polymer-Based Nanoparticle Strategies for Insulin Delivery

“…Insulin-loaded polymeric particles showed a significant decrease in BGLs by 54.19% within 4 h (from the original blood glucose concentration). In vivo studies were evaluated using a diabetic New Zealand white (NZW) rabbit model [5]. These studies serve to confirm CS has an important role to play in insulin delivery due to its unique properties, allowing for insulin to be incorporated into novel DDSes as well as into alternative routes of administration, especially orally.…”

“…Dendrimers are 3-D polymeric nanocarriers that consist of a core that can carry water-insoluble drugs and surface-active groups that help determine the properties of the dendrimer [5,43]. Polyamidoamine (PAMAM) is often used as a dendrimer due to its absorption-enhancing effects, which is important for the mucosal delivery of insulin.…”

“…To date, the advancement of nanomedicine has focused on the safe, effective, and accurate delivery of drugs for an array of pathological conditions. Studies employing biodegradable natural/synthetic polymeric nanoparticles (PNPs) and manipulating the distinctive properties of these nanomaterials for TDD have been undertaken [5].…”