Research

13 pages, 2446 KiB

Open AccessArticle

Assessment of Metabolic Interaction between Repaglinide and Quercetin via Mixed Inhibition in the Liver: In Vitro and In Vivo

by Ji-Min Kim, Seong-Wook Seo, Dong-Gyun Han, Hwayoung Yun and In-Soo Yoon

Pharmaceutics 2021, 13(6), 782; https://doi.org/10.3390/pharmaceutics13060782 - 23 May 2021

Cited by 8 | Viewed by 2680

Abstract

Repaglinide (RPG), a rapid-acting meglitinide analog, is an oral hypoglycemic agent for patients with type 2 diabetes mellitus. Quercetin (QCT) is a well-known antioxidant and antidiabetic flavonoid that has been used as an important ingredient in many functional foods and complementary medicines. This [...] Read more.

Repaglinide (RPG), a rapid-acting meglitinide analog, is an oral hypoglycemic agent for patients with type 2 diabetes mellitus. Quercetin (QCT) is a well-known antioxidant and antidiabetic flavonoid that has been used as an important ingredient in many functional foods and complementary medicines. This study aimed to comprehensively investigate the effects of QCT on the metabolism of RPG and its underlying mechanisms. The mean (range) IC₅₀ of QCT on the microsomal metabolism of RPG was estimated to be 16.7 (13.0–18.6) μM in the rat liver microsome (RLM) and 3.0 (1.53–5.44) μM in the human liver microsome (HLM). The type of inhibition exhibited by QCT on RPG metabolism was determined to be a mixed inhibition with a K_i of 72.0 μM in RLM and 24.2 μM in HLM as obtained through relevant graphical and enzyme inhibition model-based analyses. Furthermore, the area under the plasma concentration versus time curve (AUC) and peak plasma concentration (C_max) of RPG administered intravenously and orally in rats were significantly increased by 1.83- and 1.88-fold, respectively, after concurrent administration with QCT. As the protein binding and blood distribution of RPG were observed to be unaltered by QCT, it is plausible that the hepatic first-pass and systemic metabolism of RPG could have been inhibited by QCT, resulting in the increased systemic exposure (AUC and C_max) of RPG. These results suggest that there is a possibility that clinically significant pharmacokinetic interactions between QCT and RPG could occur, depending on the extent and duration of QCT intake from foods and dietary supplements. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Figure 1

15 pages, 1577 KiB

Open AccessArticle

Oleacein Intestinal Permeation and Metabolism in Rats Using an In Situ Perfusion Technique

by Anallely López-Yerena, Maria Pérez, Anna Vallverdú-Queralt, Eleftherios Miliarakis, Rosa M. Lamuela-Raventós and Elvira Escribano-Ferrer

Pharmaceutics 2021, 13(5), 719; https://doi.org/10.3390/pharmaceutics13050719 - 14 May 2021

Cited by 12 | Viewed by 2200

Abstract

Oleacein (OLEA) is one of the most important phenolic compounds in extra virgin olive oil in terms of concentration and health-promoting properties, yet there are insufficient data on its absorption and metabolism. Several non-human models have been developed to assess the intestinal permeability [...] Read more.

Oleacein (OLEA) is one of the most important phenolic compounds in extra virgin olive oil in terms of concentration and health-promoting properties, yet there are insufficient data on its absorption and metabolism. Several non-human models have been developed to assess the intestinal permeability of drugs, among them, single-pass intestinal perfusion (SPIP), which is commonly used to investigate the trans-membrane transport of drugs in situ. In this study, the SPIP model and simultaneous luminal blood sampling were used to study the absorption and metabolism of OLEA in rats. Samples of intestinal fluid and mesenteric blood were taken at different times and the ileum segment was excised at the end of the experiment for analysis by LC–ESI–LTQ–Orbitrap–MS. OLEA was mostly metabolized by phase I reactions, undergoing hydrolysis and oxidation, and metabolite levels were much higher in the plasma than in the lumen. The large number of metabolites identified and their relatively high abundance indicates an important intestinal first-pass effect during absorption. According to the results, OLEA is well absorbed in the intestine, with an intestinal permeability similar to that of the highly permeable model compound naproxen. No significant differences were found in the percentage of absorbed OLEA and naproxen (48.98 ± 12.27% and 43.96 ± 7.58%, respectively). Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Graphical abstract

16 pages, 2870 KiB

Open AccessArticle

Enhanced Bioavailability and Efficacy of Silymarin Solid Dispersion in Rats with Acetaminophen-Induced Hepatotoxicity

by Im-Sook Song, So-Jeong Nam, Ji-Hyeon Jeon, Soo-Jin Park and Min-Koo Choi

Pharmaceutics 2021, 13(5), 628; https://doi.org/10.3390/pharmaceutics13050628 - 28 Apr 2021

Cited by 21 | Viewed by 2500

Abstract

We evaluated the bioavailability, liver distribution, and efficacy of silymarin-D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) solid dispersion (silymarin-SD) in rats with acetaminophen-induced hepatotoxicity (APAP) compared with silymarin alone. The solubility of silybin, the major and active component of silymarin, in the silymarin-SD group [...] Read more.

We evaluated the bioavailability, liver distribution, and efficacy of silymarin-D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) solid dispersion (silymarin-SD) in rats with acetaminophen-induced hepatotoxicity (APAP) compared with silymarin alone. The solubility of silybin, the major and active component of silymarin, in the silymarin-SD group increased 23-fold compared with the silymarin group. The absorptive permeability of silybin increased by 4.6-fold and its efflux ratio decreased from 5.5 to 0.6 in the presence of TPGS. The results suggested that TPGS functioned as a solubilizing agent and permeation enhancer by inhibiting efflux pump. Thus, silybin concentrations in plasma and liver were increased in the silymarin-SD group and liver distribution increased 3.4-fold after repeated oral administration of silymarin-SD (20 mg/kg as silybin) for five consecutive days compared with that of silymarin alone (20 mg/kg as silybin). Based on higher liver silybin concentrations in the silymarin-SD group, the therapeutic effects of silymarin-SD in hepatotoxic rats were evaluated and compared with silymarin administration only. Elevated alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels were significantly decreased by silymarin-SD, silymarin, and TPGS treatments, but these decreases were much higher in silymarin-SD animals than in those treated with silymarin or TPGS. In conclusion, silymarin-SD (20 mg/kg as silybin, three times per day for 5 days) exhibited hepatoprotective properties toward hepatotoxic rats and these properties were superior to silymarin alone, which may be attributed to increased solubility, enhanced intestinal permeability, and increased liver distribution of the silymarin-SD formulation. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Graphical abstract

12 pages, 1744 KiB

Open AccessArticle

Physico-Chemical and In Vitro Characterization of Chitosan-Based Microspheres Intended for Nasal Administration

by Csilla Bartos, Patrícia Varga, Piroska Szabó-Révész and Rita Ambrus

Pharmaceutics 2021, 13(5), 608; https://doi.org/10.3390/pharmaceutics13050608 - 22 Apr 2021

Cited by 16 | Viewed by 2337

Abstract

The absorption of non-steroidal anti-inflammatory drugs (NSAIDs) through the nasal epithelium offers an innovative opportunity in the field of pain therapy. Thanks to the bonding of chitosan to the nasal mucosa and its permeability-enhancing effect, it is an excellent choice to formulate microspheres [...] Read more.

The absorption of non-steroidal anti-inflammatory drugs (NSAIDs) through the nasal epithelium offers an innovative opportunity in the field of pain therapy. Thanks to the bonding of chitosan to the nasal mucosa and its permeability-enhancing effect, it is an excellent choice to formulate microspheres for the increase of drug bioavailability. The aim of our work includes the preparation of spray-dried cross-linked and non-cross-linked chitosan-based drug delivery systems for intranasal application, the optimization of spray-drying process parameters (inlet air temperature, pump rate), and the composition of samples. Cross-linked products were prepared by using different amounts of sodium tripolyphosphate. On top of these, the micrometric properties, the structural characteristics, the in vitro drug release, and the in vitro permeability of the products were studied. Spray-drying resulted in micronized chitosan particles (2–4 μm) regardless of the process parameters. The meloxicam (MEL)-containing microspheres showed nearly spherical habit, while MEL was present in a molecularly dispersed state. The highest dissolved (>90%) and permeated (~45 µg/cm²) MEL amount was detected from the non-cross-linked sample. Our results indicate that spray-dried MEL-containing chitosan microparticles may be recommended for the development of a novel drug delivery system to decrease acute pain or enhance analgesia by intranasal application. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Graphical abstract

18 pages, 2534 KiB

Open AccessArticle

Developing pH-Modulated Spray Dried Amorphous Solid Dispersion of Candesartan Cilexetil with Enhanced In Vitro and In Vivo Performance

by Surendra Poudel and Dong Wuk Kim

Pharmaceutics 2021, 13(4), 497; https://doi.org/10.3390/pharmaceutics13040497 - 06 Apr 2021

Cited by 11 | Viewed by 3097

Abstract

Candesartan cilexetil (CC), a prodrug and highly effective antihypertensive agent, is a poorly soluble (BCS Class II) drug with limited bioavailability. Here, we attempted to improve CC’s bioavailability by formulating several CC-loaded amorphous solid dispersions with a hydrophilic carrier (PVPK30) and pH modifier [...] Read more.

Candesartan cilexetil (CC), a prodrug and highly effective antihypertensive agent, is a poorly soluble (BCS Class II) drug with limited bioavailability. Here, we attempted to improve CC’s bioavailability by formulating several CC-loaded amorphous solid dispersions with a hydrophilic carrier (PVPK30) and pH modifier (sodium carbonate) using the spray drying technique. Solubility, in vitro dissolution, and moisture content tests were used for screening the optimized formulation. We identified an optimized formulation of CC/PVPK30/SC, which at the ratio of 1:0.5:1 (w/w/w) exhibited a 30,000-fold increase in solubility and a more than 9-fold enhancement in dissolution compared to pure CC. Solid-state characterization revealed that in pH-modulated CC amorphous solid dispersion (CCSD_pM), CC’s crystallinity was altered to an amorphous state with the absence of undesirable interactions. Stability studies also showed that the optimized formulation was stable with good drug content and drug release under accelerated conditions of up to 4 weeks and real-time stability conditions of up to 12 weeks. Furthermore, pharmacokinetic parameters, such as AUC and C_max of candesartan, had a 4.45-fold and 7.42-fold improvement, respectively, in CCSD_pM-treated rats compared to those in the CC-treated rats. Thus, these results suggest that CCSD_pM is highly effective for increasing oral absorption. The application of these techniques can be a viable strategy to improve a drug’s bioavailability. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Graphical abstract

14 pages, 1718 KiB

Open AccessArticle

Estimating the Oral Absorption from Self-Nanoemulsifying Drug Delivery Systems Using an In Vitro Lipolysis-Permeation Method

by Mette Klitgaard, Anette Müllertz and Ragna Berthelsen

Pharmaceutics 2021, 13(4), 489; https://doi.org/10.3390/pharmaceutics13040489 - 02 Apr 2021

Cited by 11 | Viewed by 3376

Abstract

The aim of this study was to design an in vitro lipolysis-permeation method to estimate drug absorption following the oral administration of self-nanoemulsifying drug delivery systems (SNEDDSs). The method was evaluated by testing five oral formulations containing cinnarizine (four SNEDDSs and one aqueous [...] Read more.

The aim of this study was to design an in vitro lipolysis-permeation method to estimate drug absorption following the oral administration of self-nanoemulsifying drug delivery systems (SNEDDSs). The method was evaluated by testing five oral formulations containing cinnarizine (four SNEDDSs and one aqueous suspension) from a previously published pharmacokinetic study in rats. In that study, the pharmacokinetic profiles of the five formulations did not correlate with the drug solubilization profiles obtained during in vitro intestinal lipolysis. Using the designed lipolysis-permeation method, in vitro lipolysis of the five formulations was followed by in vitro drug permeation in Franz diffusion cells equipped with PermeaPad^® barriers. A linear in vivo–in vitro correlation was obtained when comparing the area under the in vitro drug permeation–time curve (AUC_0–3h), to the AUC_0–3h of the plasma concentration–time profile obtained from the in vivo study. Based on these results, the evaluated lipolysis-permeation method was found to be a promising tool for estimating the in vivo performance of SNEDDSs, but more studies are needed to evaluate the method further. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Graphical abstract

18 pages, 2031 KiB

Open AccessArticle

Characterization of P-Glycoprotein Inhibitors for Evaluating the Effect of P-Glycoprotein on the Intestinal Absorption of Drugs

by Yusuke Kono, Iichiro Kawahara, Kohei Shinozaki, Ikuo Nomura, Honoka Marutani, Akira Yamamoto and Takuya Fujita

Pharmaceutics 2021, 13(3), 388; https://doi.org/10.3390/pharmaceutics13030388 - 15 Mar 2021

Cited by 10 | Viewed by 2771

Abstract

For developing oral drugs, it is necessary to predict the oral absorption of new chemical entities accurately. However, it is difficult because of the involvement of efflux transporters, including P-glycoprotein (P-gp), in their absorption process. In this study, we conducted a comparative analysis [...] Read more.

For developing oral drugs, it is necessary to predict the oral absorption of new chemical entities accurately. However, it is difficult because of the involvement of efflux transporters, including P-glycoprotein (P-gp), in their absorption process. In this study, we conducted a comparative analysis on the inhibitory activities of seven P-gp inhibitors (cyclosporin A, GF120918, LY335979, XR9576, WK-X-34, VX-710, and OC144-093) to evaluate the effect of P-gp on drug absorption. GF120918, LY335979, and XR9576 significantly decreased the basal-to-apical transport of paclitaxel, a P-gp substrate, across Caco-2 cell monolayers. GF120918 also inhibited the basal-to-apical transport of mitoxantrone, a breast cancer resistance protein (BCRP) substrate, in Caco-2 cells, whereas LY335979 hardly affected the mitoxantrone transport. In addition, the absorption rate of paclitaxel after oral administration in wild-type mice was significantly increased by pretreatment with LY335979, and it was similar to that in mdr1a/1b knockout mice. Moreover, the absorption rate of topotecan, a BCRP substrate, in wild-type mice pretreated with LY335979 was similar to that in mdr1a/1b knockout mice but significantly lower than that in bcrp knockout mice. These results indicate that LY335979 has a selective inhibitory activity for P-gp, and would be useful for evaluating the contribution of P-gp to drug absorption. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Figure 1

13 pages, 2178 KiB

Open AccessArticle

Study of the l-Phenylalanine Ammonia-Lyase Penetration Kinetics and the Efficacy of Phenylalanine Catabolism Correction Using In Vitro Model Systems

by Lyubov Dyshlyuk, Stanislav Sukhikh, Svetlana Noskova, Svetlana Ivanova, Alexander Prosekov and Olga Babich

Pharmaceutics 2021, 13(3), 383; https://doi.org/10.3390/pharmaceutics13030383 - 13 Mar 2021

Cited by 1 | Viewed by 2278

Abstract

The kinetics of l-phenylalanine ammonia-lyase (PAL) penetration into the monolayer of liver cells after its release from capsules was studied. The studies showed the absence of the effect of the capsule shell based on plant hydrocolloids on the absorption of l-phenylalanine [...] Read more.

The kinetics of l-phenylalanine ammonia-lyase (PAL) penetration into the monolayer of liver cells after its release from capsules was studied. The studies showed the absence of the effect of the capsule shell based on plant hydrocolloids on the absorption of l-phenylalanine ammonia-lyase in systems simulating the liver surface. After 120 min of incubation, in all variants of the experiment, from 87.0 to 96.8% of the enzyme penetrates the monolayer of liver cells. The combined analysis of the results concludes that the developed encapsulated form of l-phenylalanine ammonia-lyase is characterized by high efficiency in correcting the disturbed catabolism of phenylalanine in phenylketonuria, which is confirmed by the results of experiments carried out on in vitro model systems. PAL is approved for the treatment of adult patients with phenylketonuria. The encapsulated l-phenylalanine ammonia-lyase form can find therapeutic application in the phenylketonuria treatment after additional in vitro and in vivo studies, in particular, the study of preparation safety indicators. Furthermore, it demonstrated high efficacy in tumor regression and the treatment of tyrosine-related metabolic disorders such as tyrosinemia. Several therapeutically valuable metabolites biosynthesized by PAL via its catalytic action are included in food supplements, antimicrobial peptides, drugs, amino acids, and their derivatives. PAL, with improved pharmacodynamic and pharmacokinetic properties, is a highly effective medical drug. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Figure 1

19 pages, 3875 KiB

Open AccessArticle

Dose-Dependent Solubility–Permeability Interplay for Poorly Soluble Drugs under Non-Sink Conditions

by Kazuya Sugita, Noriyuki Takata and Etsuo Yonemochi

Pharmaceutics 2021, 13(3), 323; https://doi.org/10.3390/pharmaceutics13030323 - 02 Mar 2021

Cited by 8 | Viewed by 2613

Abstract

We investigated the solubility–permeability interplay using a solubilizer additive under non-sink conditions. Sodium lauryl sulfate (SLS) was used as a solubilizer additive. The solubility and permeability of two poorly soluble drugs at various doses, with or without SLS, were evaluated by flux measurements. [...] Read more.

We investigated the solubility–permeability interplay using a solubilizer additive under non-sink conditions. Sodium lauryl sulfate (SLS) was used as a solubilizer additive. The solubility and permeability of two poorly soluble drugs at various doses, with or without SLS, were evaluated by flux measurements. The total permeated amount of griseofulvin, which has high permeability, increased by the addition of SLS. On the other hand, triamcinolone, which has low permeability, showed an almost constant rate of permeation regardless of the SLS addition. The total permeated amount of griseofulvin increased by about 20–30% when the dose amount exceeded its solubility, whereas its concentration in the donor chamber remained almost constant. However, the total permeated amount of triamcinolone was almost constant regardless of dose amount. These results suggest that the permeability of the unstirred water layer (UWL) may be affected by SLS and solid drugs for high-permeable drugs. The effect of solid drugs could be explained by a reduction in the apparent UWL thickness. For the appropriate evaluation of absorption, it would be essential to consider these effects. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Figure 1

12 pages, 1389 KiB

Open AccessArticle

Solubility, Permeability, and Dissolution Rate of Naftidrofuryl Oxalate Based on BCS Criteria

by Marta Kus-Slowinska, Monika Wrzaskowska, Izabela Ibragimow, Piotr Igor Czaklosz, Anna Olejnik and Hanna Piotrowska-Kempisty

Pharmaceutics 2020, 12(12), 1238; https://doi.org/10.3390/pharmaceutics12121238 - 19 Dec 2020

Cited by 3 | Viewed by 3273

Abstract

The Biopharmaceutics Classification System (BCS) was conceived to classify drug substances by their in vitro aqueous solubility and permeability properties. The essential activity of naftidrofuryl oxalate (NF) has been described as the inhibition of the serotonin receptors (5-HT₂), resulting in vasodilation [...] Read more.

The Biopharmaceutics Classification System (BCS) was conceived to classify drug substances by their in vitro aqueous solubility and permeability properties. The essential activity of naftidrofuryl oxalate (NF) has been described as the inhibition of the serotonin receptors (5-HT₂), resulting in vasodilation and decreasing blood pressure. Since the early 1980s, NF has been used to treat several venous and cerebral diseases. There is no data available on the BCS classification of NF. However, based on its physical-chemical properties, NF might be considered to belong to the 1st or the 3rd BCS class. The present study aimed to provide data concerning the solubility and permeability of NF through Caco-2 monolayers and propose its preliminary classification into BCS. We showed that NF is a highly soluble and permeable drug substance; thus, it might be suggested to belong to BCS class I. Additionally, a high dissolution rate of the encapsulated NF based on Praxilene^® 100 mg formulation was revealed. Hence, it might be considered as an immediate-release (IR). Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Graphical abstract

11 pages, 4508 KiB

Open AccessArticle

Development of Lipid–Polymer Hybrid Nanoparticles for Improving Oral Absorption of Enoxaparin

by Bo Tang, Yu Qian and Guihua Fang

Pharmaceutics 2020, 12(7), 607; https://doi.org/10.3390/pharmaceutics12070607 - 30 Jun 2020

Cited by 18 | Viewed by 2562

Abstract

Enoxaparin, an anticoagulant that helps prevent the formation of blood clots, is administered parenterally. Here, we report the development and evaluation of lipid–polymer hybrid nanoparticles (LPHNs) for the oral delivery of enoxaparin. The polymer poloxamer 407 (P407) was incorporated into lipid nanoparticles to [...] Read more.

Enoxaparin, an anticoagulant that helps prevent the formation of blood clots, is administered parenterally. Here, we report the development and evaluation of lipid–polymer hybrid nanoparticles (LPHNs) for the oral delivery of enoxaparin. The polymer poloxamer 407 (P407) was incorporated into lipid nanoparticles to form gel cores and ensure high encapsulation efficiency and the controlled release of enoxaparin. In vitro results indicated that 30% of P407 incorporation offered higher encapsulation efficiency and sustained the release of enoxaparin. Laser confocal scanning microscopy (LCSM) images showed that LPHNs could not only significantly improve the accumulation of enoxaparin in intestinal villi but also facilitate enoxaparin transport into the underlayer of intestinal epithelial cells. In vivo pharmacokinetic study results indicated that the oral bioavailability of enoxaparin was markedly increased about 6.8-fold by LPHNs. In addition, its therapeutic efficacy against pulmonary thromboembolism was improved 2.99-fold by LPHNs. Moreover, LPHNs exhibited excellent biocompatibility in the intestine. Overall, the LPHN is a promising delivery carrier to boost the oral absorption of enoxaparin. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Figure 1

12 pages, 3961 KiB

Open AccessArticle

Hydrogel Formulations Incorporating Drug Nanocrystals Enhance the Therapeutic Effect of Rebamipide in a Hamster Model for Oral Mucositis

by Noriaki Nagai, Ryotaro Seiriki, Saori Deguchi, Hiroko Otake, Noriko Hiramatsu, Hiroshi Sasaki and Naoki Yamamoto

Pharmaceutics 2020, 12(6), 532; https://doi.org/10.3390/pharmaceutics12060532 - 09 Jun 2020

Cited by 8 | Viewed by 3139

Abstract

A mouthwash formulation of rebamipide (REB) is commonly used to treat oral mucositis; however, this formulation does not provide sufficient treatment or prevention in cases of serious oral mucositis. To improve treatment, we attempted to design a hydrogel incorporating REB nanocrystals (R-NPs gel). [...] Read more.

A mouthwash formulation of rebamipide (REB) is commonly used to treat oral mucositis; however, this formulation does not provide sufficient treatment or prevention in cases of serious oral mucositis. To improve treatment, we attempted to design a hydrogel incorporating REB nanocrystals (R-NPs gel). The R-NPs gel was prepared by a bead mill method using carbopol hydrogel, methylcellulose and 2-hydroxypropyl-β-cyclodextrin, and another hydrogel incorporating REB microcrystals (R-MPs gel) was prepared following the same protocol but without the bead mill treatment. The REB particle size in the R-MPs gel was 0.15–25 μm, and while the REB particle size was 50–180 nm in the R-NPs gel. Next, we investigated the therapeutic effect of REB nanocrystals on oral mucositis using a hamster model. Almost all of the REB was released as drug nanocrystals from the R-NPs gel, and the REB content in the cheek pouch of hamsters treated with R-NPs gel was significantly higher than that of hamsters treated with R-MPs gel. Further, treatment with REB hydrogels enhanced the healing of oral wounds in the hamsters. REB accumulation in the cheek pouch of hamsters treated with the R-NPs gel was prevented by an inhibitor of clathrin-dependent endocytosis (CME) (40 μM dynasore). In conclusion, we designed an R-NPs gel and found that REB nanocrystals are taken up by tissues through CME, where they provide a persistent effect resulting in an enhancement of oral wound healing. Full article

(This article belongs to the Special Issue Drug Absorption Studies: In Situ, In Vitro and In Silico Models)

► Show Figures

Graphical abstract

Journal Menu

Journal Browser

Drug Absorption Studies: In Situ, In Vitro and In Silico Models

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (12 papers)

Research

Further Information

Guidelines

MDPI Initiatives

Follow MDPI