pH-Responsive and Mucoadhesive Nanoparticles for Enhanced Oral Insulin Delivery: The Effect of Hyaluronic Acid with Different Molecular Weights

Abstract

Drug degradation at low pH and rapid clearance from intestinal absorption sites are the main factors limiting the development of oral macromolecular delivery systems. Based on the pH responsiveness and mucosal adhesion of hyaluronic acid (HA) and poly[2-(dimethylamino)ethyl methacrylate] (PDM), we prepared three HA–PDM nano-delivery systems loaded with insulin (INS) using three different molecular weights (MW) of HA (L, M, H), respectively. The three types of nanoparticles (L/H/M-HA–PDM–INS) had uniform particle sizes and negatively charged surfaces. The optimal drug loadings of the L-HA–PDM–INS, M-HA–PDM–INS, H-HA–PDM–INS were 8.69 ± 0.94%, 9.11 ± 1.03%, and 10.61 ± 1.16% (w/w), respectively. The structural characteristics of HA–PDM–INS were determined using FT-IR, and the effect of the MW of HA on the properties of HA–PDM–INS was investigated. The release of INS from H-HA–PDM–INS was 22.01 ± 3.84% at pH 1.2 and 63.23 ± 4.10% at pH 7.4. The protective ability of HA–PDM–INS with different MW against INS was verified by circular dichroism spectroscopy and protease resistance experiments. H-HA–PDM–INS retained 45.67 ± 5.03% INS at pH 1.2 at 2 h. The biocompatibility of HA–PDM–INS, regardless of the MW of HA, was demonstrated using CCK-8 and live–dead cell staining. Compared with the INS solution, the transport efficiencies of L-HA–PDM–INS, M-HA–PDM–INS, and H-HA–PDM–INS increased 4.16, 3.81, and 3.10 times, respectively. In vivo pharmacodynamic and pharmacokinetic studies were performed in diabetic rats following oral administration. H-HA–PDM–INS exhibited an effective hypoglycemic effect over a long period, with relative bioavailability of 14.62%. In conclusion, these simple, environmentally friendly, pH-responsive, and mucoadhesive nanoparticles have the potential for industrial development. This study provides preliminary data support for oral INS delivery.

LA67 Liposome-Loaded Thermo-Sensitive Hydrogel with Active Targeting for Efficient Treatment of Keloid via Peritumoral Injection

“…The blood biochemical analysis was performed for bio-safety evaluation, including creatinine (CREA), alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), and blood urea nitrogen (BUN) [ 28 ]. The serum was separated by centrifugation at 4 °C, 4000 rpm.…”

Muco-Adhesive and Muco-Penetrative Formulations for the Oral Delivery of Insulin

“…The HA can also enhance the MA properties of the nanoparticles and improve their biocompatibility. 37 P(AA-g-EG) hydrogels act as promising MA drug carriers with pH-responsive properties. The hydrogen bond between the PEG chains and the PAA backbone breaks when the pH becomes more basic due to ionization of the carboxylic groups.…”

“…Additionally, PDM is combined with another polymer, hyaluronic acid (HA), to improve the stability and versatility of the delivery system. The HA can also enhance the MA properties of the nanoparticles and improve their biocompatibility …”

Synergistic Effects of Chemotherapy and Phototherapy on Ovarian Cancer Using Follicle-Stimulating Hormone Receptor-Mediated Liposomes Co-Loaded with SN38 and IR820

“…The detection wavelength of SN38 was 265 nm, and methanol:water (70:30) was used as the mobile phase. Free SN38 and IR820 were separated from the liposomes using minicolumn centrifugation [17]. The entrapment efficiency (EE%) was calculated as follows: EE (%) = (weight of encapsulated drug)/(weight of total drug) × 100% To determine the stability of SN38/IR820-Lipo@FSH, the prepared solution was stored at 4 • C for 7 days in PBS or PBS containing 50% of serum.…”