Enhanced bioavailability of poorly absorbed hydrophilic compounds through drug complex/in situ gelling formulation

Dai, Wei; Liang, Dong; Song, Yanqiu

doi:10.1016/j.ijpharm.2013.07.066

Cited by 12 publications

(5 citation statements)

References 39 publications

(44 reference statements)

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“… 44 The HIP-nanocomplex may synchronize the diffusion of insulin with SGDC bile salt at the absorption site and thus maintain maximum concentration gradients, increasing the permeability of insulin across TR146 cell layers. 45 As corroborated by previous investigations, because of the generation of reverse micelles, bile salts may increase the transcellular transport of hydrophilic drugs by forming aqueous channels. 46 Furthermore, owing to the extraction of membrane lipids, bile salts can enhance the transcellular pathways by forming micelles at high concentrations.…”

Section: Resultssupporting

confidence: 59%

Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation

Bashyal¹,

Seo²,

Keum³

et al. 2021

IJN

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Background:The clinical use of therapeutic peptides has been limited because of their inefficient delivery approaches and, therefore, inadequate delivery to target sites. Buccal administration of therapeutic peptides offers patients a potential alternative to the current invasive routes of administration. Purpose: The aim of the study was to fabricate hydrophobic ion-pairing (HIP)-nanocomplexes (C1 and C2) utilizing anionic bile salts and cationic peptides, and to assess their permeability across TR146 buccal cell layers and porcine buccal tissue. Methods: C1 and C2-nanocomplexes were fabricated using the HIP approach. In addition, their physiochemical and morphological attributes, in vitro and ex vivo permeability properties, and qualitative and quantitative cellular uptake were evaluated and compared. The localization of C1 and C2-nanocomplexes in porcine buccal tissue was determined using confocal laser scanning microscopy. Results: The C1-nanocomplex was the superior nanocarrier and significantly enhanced the transport of insulin across TR146 cell layers and porcine buccal tissue, exhibiting a 3.00-and 51.76-fold increase in permeability coefficient, respectively, when compared with insulin solution (p < 0.01). C1-nanocomplex was more efficient than C2-nanocomplex at facilitating insulin permeability, with a 2.18-and 27.64-fold increase across TR146 cell layers and porcine buccal tissue, respectively. The C1-nanocomplex demonstrated immense uptake and localization of insulin in TR146 cells and porcine buccal tissue, as evidenced by a highly intense fluorescence in TR146 cells, and a great shift of fluorescence intensity towards the inner region of buccal tissue over time. The increase in fluorescence intensity was observed in the order of C1 > C2 > insulin solution. Conclusion:In this study, we highlighted the efficacy of potential nanocarriers in addressing the daunting issues associated with the invasive administration of insulin and indicated a promising strategy for the buccal administration and delivery of this life-saving peptide hormone.

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Section: Resultssupporting

confidence: 59%

Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation

Bashyal¹,

Seo²,

Keum³

et al. 2021

IJN

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“…Similarly, the intracellular uptake of QCN-NE was also significantly increased compared with that of QCN in 0.3% NaCMC ( Figure 4 A). These observations suggest that nano-sized oil droplets enhanced the passive transport of QCN through the intestinal walls and that formulation components, such as Labrasol and Cremophor EL, modified the properties of the epithelial barrier, thereby enhancing cellular permeability [ 48 , 52 ].…”

Section: Resultsmentioning

confidence: 99%

Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin

et al. 2018

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Co-administration of conventional and natural chemotherapeutics offers synergistic anticancer efficacy while minimizing adverse effects. In this study, an oral co-delivery system for pemetrexed (PMX) and quercetin (QCN) was designed based on water-in-oil-in-water nanoemulsion (NE), which is highly absorbable because it enhances the intestinal membrane permeability of PMX and aqueous solubility of QCN. To create this system, an ion-pairing complex of PMX with Nα-deoxycholyl-l-lysyl-methylester (DCK) was formed and further incorporated with QCN into the NE, yielding PMX/DCK-QCN-NE. The results revealed synergistic inhibitory effects on human lung carcinoma (A549) cell proliferation and migration after combined treatment with PMX/DCK and QCN. The intestinal membrane permeability and cellular uptake of PMX/DCK and QCN from the NE were significantly improved via facilitated transport of PMX by the interaction of DCK with bile acid transporters, as well as NE formulation-mediated alterations in the membrane structure and fluidity, which resulted in 4.51- and 23.9-fold greater oral bioavailability of PMX and QCN, respectively, than each free drug. Tumor growth in A549 cell-bearing mice was also maximally suppressed by 62.7% after daily oral administration of PMX/DCK-QCN-NE compared with controls. Thus, PMX/DCK-QCN-NE is a promising oral nanocarrier of PMX and QCN for synergistic anticancer efficacy and long-term chemotherapy.

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“…Few works have been published on in situ gelling formulations for oral delivery of drugs. In particular, Daia et al incorporated a Class III drug/permeation enhancer complex into an in situ gelling vehicle, represented by Cremophor [ 89 ]. The aim was to minimize the dilution effect of the formulations in the gastrointestinal lumen and to synchronize the diffusion of both a drug and a permeation enhancer to the duodenum that was the absorption site.…”

Section: Gastrointestinal Routementioning

confidence: 99%

Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

et al. 2020

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In situ gelling drug delivery systems have gained enormous attention over the last decade. They are in a sol-state before administration, and they are capable of forming gels in response to different endogenous stimuli, such as temperature increase, pH change and the presence of ions. Such systems can be administered through different routes, to achieve local or systemic drug delivery and can also be successfully used as vehicles for drug-loaded nano- and microparticles. Natural, synthetic and/or semi-synthetic polymers with in situ gelling behavior can be used alone, or in combination, for the preparation of such systems; the association with mucoadhesive polymers is highly desirable in order to further prolong the residence time at the site of action/absorption. In situ gelling systems include also solid polymeric formulations, generally obtained by freeze-drying, which, after contact with biological fluids, undergo a fast hydration with the formation of a gel able to release the drug loaded in a controlled manner. This review provides an overview of the in situ gelling drug delivery systems developed in the last 10 years for non-parenteral administration routes, such as ocular, nasal, buccal, gastrointestinal, vaginal and intravesical ones, with a special focus on formulation composition, polymer gelation mechanism and in vitro release studies.

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Enhanced bioavailability of poorly absorbed hydrophilic compounds through drug complex/in situ gelling formulation

Cited by 12 publications

References 39 publications

Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation

Facilitated Buccal Insulin Delivery via Hydrophobic Ion-Pairing Approach: In vitro and ex vivo Evaluation

Preparation, Characterization, and In Vivo Evaluation of an Oral Multiple Nanoemulsive System for Co-Delivery of Pemetrexed and Quercetin

Recent Advances in the Development of In Situ Gelling Drug Delivery Systems for Non-Parenteral Administration Routes

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