pH-sensitive O-carboxymethyl chitosan/sodium alginate nanohydrogel for enhanced oral delivery of insulin

Zhang, Haibin; Gu, Zhou; Li, Wenya; Guo, Lili; Wang, Litong; Guo, Lei; Ma, Saibo; Han, Baoqin; Chang, Jing

doi:10.1016/j.ijbiomac.2022.10.274

Cited by 37 publications

(14 citation statements)

References 62 publications

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“…Another phenomenon was also noted: the DL of the NPs increased with an increase in the INS dose, but the EE decreased significantly. Similar results have been reported previously [ 53 , 54 ]. The excessive INS perhaps approached the upper limit of the EE of the NPs and damaged the equilibrium of the loading process.…”

Section: Resultssupporting

confidence: 93%

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

et al. 2023

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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.

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Section: Resultssupporting

confidence: 93%

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

et al. 2023

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“…Here, the surface potential of CIP + NAR–CM–CS/AG–NPs was recorded as very less positive, indicating that the methyl carboxylation brings down the positive charge significantly due to the formation of carboxylate ion (CH 2 COO – ). The balance in positive and negative surface charge over NPs due to NH 3 + and carboxylate ion (CH 2 COO – ) contributed toward the stability and robustness of the system and impersonated the stability in the biological medium . The particle size and their distribution and surface charge on NPs are shown in Figures and .…”

Section: Resultsmentioning

confidence: 99%

Co-Delivery of Naringin and Ciprofloxacin by Oleic Acid Lipid Core Encapsulated in Carboxymethyl Chitosan/Alginate Nanoparticle Composite for Enhanced Antimicrobial Activity

Almeleebia,

Akhter,

Khalilullah

et al. 2024

ACS Omega

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A novel combination of antibiotic, ciprofloxacin (CIP) with herbal counterpart naringin (NAR) was encapsulated by an oleic acid lipid core and carboxymethyl chitosan (CM−CS)/Alginate (AG) nanoparticle composite (CIP + NAR−CM−CS/AG−NPs) for improved antimicrobial efficacy of antibiotic. Herein, this study explored the design and preparation of a composite system that enables to deliver both CIP and NAR from the oleic acid lipid core of CM− CS/AG nanoparticles using a nonsolvent ionic gelation technique. The nanoparticles (NPs) were fabricated with improved long-acting antimicrobial activity against E. coli and S. aureus. The optimized composition was investigated for physicochemical properties particle size, particle distribution, and ζ−potential. A diverse array of analytical tools was employed to characterize the optimized formulation including DSC, XRD, Malvern Zetasizer for particle size, ζ−potential, TEM, and SEM. Further, the preparation was investigated for % drug release, flux determination, antioxidant, and antimicrobial activity. The formulation stability was tested for 90 days and also evaluated formulation stability in fetal bovine serum to inspect the modification in physicochemical characteristics. NPs size was determined at 85 nm, PDI, and ζ−potential was recorded at 0.318, and 0.7 ± 0.4 mV. The % CIP and NAR entrapment efficiency and % loading were incurred as 91 ± 1.9, and 89.5 ± 1.2; 11.5 ± 0.6, and 10.8 ± 0.5%, respectively. The drug release erupted in the beginning phase followed by sustained and prolonged release for 48 h. The analytical experiments by DSC ensured the noninteracting and safe use of excipients in combination. X−ray studies demonstrated the amorphous state of the drug in the formulation. The insignificant alteration of formulation characteristics in FBS suggested stable and robust preparation. Storage stability of the developed formulation ensured consistent and uniform stability for three months. The DPPH assays demonstrated that NAR had good antioxidant capacity and supported improving antimicrobial activity of CIP. The hemolytic test suggested the developed formulation was compatible and caused insignificant RBC destruction. The in-house built formulation CIP + NAR−CM−CS/AG−NPs significantly improved the antimicrobial activity compared to CIP alone, offering a novel choice in antimicrobial application.

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“…The liraglutide release profiles from different formulations were tested by an in vitro assay. The pH was set to 1.2 and 6.8 to simulate the acidic environment of gastric and intestinal fluids in vivo, respectively [ 31 ]. As shown in Figure 5 a, the amount of liraglutide released from CLs/AT-CLs is approximately 80% at 8 h, unlike the liraglutide released from the PcCLs/Pc-AT-CLs, which is significantly slower at approximately 55%.…”

Section: Resultsmentioning

confidence: 99%

Preparation, Drug Distribution, and In Vivo Evaluation of the Safety of Protein Corona Liposomes for Liraglutide Delivery

Ding

Zhao

et al. 2023

Nanomaterials

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The development of oral drug delivery systems is challenging, and issues related to the mucus layer and low intestinal epithelial permeability have not yet been surmounted. The purpose of this study was to develop a promising formulation that is more adapted to in vivo absorption and to facilitate the administration of oral liraglutide. Cationic liposomes (CLs) linked to AT-1002 were prepared using a double-emulsion method, and BSA was adsorbed on the surface of the AT-CLs, resulting in protein corona cationic liposomes with AT-1002 (Pc-AT-CLs). The preparation method was determined by investigating various process parameters. The particle size, potential, and encapsulation efficiency (EE%) of the Pc-AT-CLs were 202.9 ± 12.4 nm, 1.76 ± 4.87 mV, and 84.63 ± 5.05%, respectively. The transmission electron microscopy (TEM) imaging revealed a nearly spherical structure of the Pc-AT-CLs, with a recognizable coating. The circular dichroism experiments confirmed that the complex preparation process did not affect the secondary structure of liraglutide. With the addition of BSA and AT-1002, the mucosal accumulation of the Pc-AT-CLs was nearly two times lower than that of the AT-CLs, and the degree of enteric metaplasia was 1.35 times higher than that of the PcCLs. The duration of the intestinal absorption of the Pc-AT-CLs was longer, offering remarkable biological safety.

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pH-sensitive O-carboxymethyl chitosan/sodium alginate nanohydrogel for enhanced oral delivery of insulin

Cited by 37 publications

References 62 publications

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

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

Co-Delivery of Naringin and Ciprofloxacin by Oleic Acid Lipid Core Encapsulated in Carboxymethyl Chitosan/Alginate Nanoparticle Composite for Enhanced Antimicrobial Activity

Preparation, Drug Distribution, and In Vivo Evaluation of the Safety of Protein Corona Liposomes for Liraglutide Delivery

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