Nintedanib-cyclodextrin complex to improve bio-activity and intestinal permeability

Vaidya, Bhuvaneshwar; Shukla, Snehal K.; Kolluru, Srikanth; Huen, Melanie; Mulla, Nihal S.; Mehra, Neelesh Kumar; Kanabar, Dipti; Palakurthi, Srinath; Ayehunie, Seyoum; Muth, Aaron; Gupta, Vivek

doi:10.1016/j.carbpol.2018.09.080

Cited by 61 publications

(26 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The common types of CD are alpha (α), beta (β), and gamma (γ) CDs formed by six, seven, and eight α-D-glucopyranose units, respectively. Among the three CDs, βCD (Figure 1B) is the most commonly used in many pharmaceutical purposes due to its low price, easy synthetic access, and structural orientation suitable for inclusion complex generation [19,20]. However, the low water solubility (18.5 mg/mL at 25 °C) and nephrotoxicity of βCD limit its use for practical applications [21].…”

Section: Introductionmentioning

confidence: 99%

Enhanced Solubility and Anticancer Potential of Mansonone G By β-Cyclodextrin-Based Host-Guest Complexation: A Computational and Experimental Study

et al. 2019

View full text Add to dashboard Cite

Mansonone G (MG), a plant-derived compound isolated from the heartwood of Mansonia gagei, possesses a potent antitumor effect on several kinds of malignancy. However, its poor solubility limits the use for practical applications. Beta-cyclodextrin (βCD), a cyclic oligosaccharide composed of seven (1→4)-linked α-D-glucopyranose units, is capable of encapsulating a variety of poorly soluble compounds into its hydrophobic interior. In this work, we aimed to enhance the water solubility and the anticancer activity of MG by complexation with βCD and its derivatives (2,6-di-O-methyl-βCD (DMβCD) and hydroxypropyl-βCD). The 90-ns molecular dynamics simulations and MM/GBSA-based binding free energy results suggested that DMβCD was the most preferential host molecule for MG inclusion complexation. The inclusion complex formation between MG and βCD(s) was confirmed by DSC and SEM techniques. Notably, the MG/βCDs inclusion complexes exerted significantly higher cytotoxic effect (~2–7 fold) on A549 lung cancer cells than the uncomplexed MG.

show abstract

Section: Introductionmentioning

confidence: 99%

Enhanced Solubility and Anticancer Potential of Mansonone G By β-Cyclodextrin-Based Host-Guest Complexation: A Computational and Experimental Study

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Native or non-substituted CDs and their hydroxy-propyl derivatives have been used as pharmaceutical excipients to increase drug solubility, improve chemical stability, reduce toxicity and transport molecules to specific sites [19,20,21,22,23]. Importantly, drug/CD complexation increases the aqueous solubility of poorly soluble drugs without altering their properties [24]; as a result, CDs have been used in over 40 marketed products to date.…”

Section: Introductionmentioning

confidence: 99%

Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation

2019

View full text Add to dashboard Cite

The topical administration route is commonly used for targeting therapeutics to the eye; however, improving the bioavailability of drugs applied directly to the eye remains a challenge. Different strategies have been studied to address this challenge. One of them is the use of aggregates that are formed easily by self-assembly of cyclodextrin (CD)/drug complexes in aqueous solution. The aim of this study was to design a new eye drop formulation based on aggregates formed between CD/drug complexes. For this purpose, the physicochemical properties of the aggregates associated with six CDs and selected water-soluble polymers were analysed. Complex formation was studied using differential scanning calorimetry (DSC), Fourier-transform infrared spectroscopy (FT-IR) and 1H nuclear magnetic resonance spectroscopy (1H-NMR). Results showed that HPβCD performed best in terms of solubilization, while γCD performed best in terms of enhancing nanoaggregate formation. Formation of inclusion complexes was confirmed by DSC, FT-IR and 1H-NMR studies. A mixture of 15% (w/v) γCD and 8% (w/v) HPβCD was selected for formulation studies. It was concluded that formulations with aggregate sizes less than 1 µm and viscosity around 10–19 centipoises can be easily prepared using a mixture of CDs. Formulations containing polymeric drug/CD nanoaggregates represent an interesting strategy for enhanced topical delivery of nepafenac.

show abstract

“…In another study, the effect of enhancers on the permeation of low permeability drugs was demonstrated using the EpiIntestinal tissue model. Complexing the low permeability, idiopathic pulmonary fibrosis drug, Nintedanib, with cyclodextrin was shown to significantly increase absorption and bioavailability across the intestinal barrier (Vaidyaa et al 2019). Recently, Marrella et al (2020) utilized in a flow system to monitor the absorption of two non-metabolized sugars, lactulose and mannitol, in EpiIntestinal tissues grown under standard (healthy) and pathological conditions (EGTA-induced barrier disruption).…”

Section: Structure and Cellular Phenotypes Of Small Intestinal Epithementioning

confidence: 99%

Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays

Markus¹,

Landry

Stevens

et al. 2020

In Vitro Cell.Dev.Biol.-Animal

Self Cite

View full text Add to dashboard Cite

The gastrointestinal tract (GIT), in particular, the small intestine, plays a significant role in food digestion, fluid and electrolyte transport, drug absorption and metabolism, and nutrient uptake. As the longest portion of the GIT, the small intestine also plays a vital role in protecting the host against pathogenic or opportunistic microbial invasion. However, establishing polarized intestinal tissue models in vitro that reflect the architecture and physiology of the gut has been a challenge for decades and the lack of translational models that predict human responses has impeded research in the drug absorption, metabolism, and drug-induced gastrointestinal toxicity space. Often, animals fail to recapitulate human physiology and do not predict human outcomes. Also, certain human pathogens are species specific and do not infect other hosts. Concerns such as variability of results, a low throughput format, and ethical considerations further complicate the use of animals for predicting the safety and efficacy xenobiotics in humans. These limitations necessitate the development of in vitro 3D human intestinal tissue models that recapitulate in vivo-like microenvironment and provide more physiologically relevant cellular responses so that they can better predict the safety and efficacy of pharmaceuticals and toxicants. Over the past decade, much progress has been made in the development of in vitro intestinal models (organoids and 3D-organotypic tissues) using either inducible pluripotent or adult stem cells. Among the models, the MatTek's intestinal tissue model (EpiIntestinal™ Ashland, MA) has been used extensively by the pharmaceutical industry to study drug permeation, metabolism, drug-induced GI toxicity, pathogen infections, inflammation, wound healing, and as a predictive model for a clinical adverse outcome (diarrhea) to pharmaceutical drugs. In this paper, our review will focus on the potential of in vitro small intestinal tissues as preclinical research tool and as alternative to the use of animals.

show abstract

Nintedanib-cyclodextrin complex to improve bio-activity and intestinal permeability

Cited by 61 publications

References 40 publications

Enhanced Solubility and Anticancer Potential of Mansonone G By β-Cyclodextrin-Based Host-Guest Complexation: A Computational and Experimental Study

Enhanced Solubility and Anticancer Potential of Mansonone G By β-Cyclodextrin-Based Host-Guest Complexation: A Computational and Experimental Study

Nepafenac-Loaded Cyclodextrin/Polymer Nanoaggregates: A New Approach to Eye Drop Formulation

Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays

Contact Info

Product

Resources

About