Cyclodextrin Complexation for Enhanced Stability and Non-invasive Pulmonary Delivery of Resveratrol—Applications in Non-small Cell Lung Cancer Treatment

Wang, Xuechun; Parvathaneni, Vineela; Shukla, Snehal K.; Kanabar, Dipti; Muth, Aaron; Gupta, Vivek

doi:10.1208/s12249-020-01724-x

Cited by 34 publications

(20 citation statements)

References 54 publications

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“…In this study, complexes of BDQ with SBE-βCD were prepared and the impact on aqueous solubility of BDQ was evaluated. In many of our recent studies, we have reported SBE-β-CD to enhance the solubility and stability significantly, compared to other CD types [ 17 , 25 , 28 , 29 ]. As shown in Figure 1 B, the solubility of BDQ linearly increased with increasing concentration of SBE-β-CD in water, which indicates that the phase solubility curve represents an A L -type system [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

“…A stable complex ensures stronger interactions between the guest molecules (drug) and host molecules (SBE-β-CD) that may improve the solubility and therapeutic activity of the drug [ 28 ]. In addition, the complexation efficiency (CE) was found to be 0.4 (reported average for cyclodextrin complexes is 0.3), indicating that on average, only about one out of every three cyclodextrin molecules present in a given complexation medium is in the complex for hydrophobic drug molecules [ 25 ]. Angiolini et al prepared cyclodextrin inclusion complexes of rifampicin (anti-tuberculosis agent) and observed an improvement in aqueous solubility by 23-fold when using methylated cyclodextrin, heptakis (2,6-diO-methyl)-β-cyclodextrin [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

“…By complexation with β-cyclodextrin, the authors increased the aqueous solubility of ethionamide and booster molecule 10 and 90 fold, respectively [ 32 ]. In an earlier study published by our group, a 66-fold increase in solubility was reported for resveratrol after complexation with SBE-β-CD [ 25 ]. In the current study, a superior solubility enhancement (2800-fold) of BDQ was observed after complexation signifying the inclusion complex formation.…”

Section: Resultsmentioning

confidence: 99%

“…Accumulation into the deep lungs is imperative for treatment of NSCLC [ 22 , 23 ]. Especially, accumulation of drug-cyclodextrin complexes in the lungs after pulmonary delivery has been studied by several researchers and an improved efficacy through CD complexation in NSCLC has been reported earlier [ 24 , 25 , 26 , 27 ]. To date, there have been no studies on the inclusion complexation of BDQ using cyclodextrins.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Parvathaneni

Elbatanony

Goyal

et al. 2021

IJMS

Self Cite

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There is growing evidence that repurposed drugs demonstrate excellent efficacy against many cancers, while facilitating accelerated drug development process. In this study, bedaquiline (BDQ), an FDA approved anti-mycobacterial agent, was repurposed and an inhalable cyclodextrin complex formulation was developed to explore its anti-cancer activity in non-small cell lung cancer (NSCLC). A sulfobutyl ether derivative of β-cyclodextrin (SBE-β-CD) was selected based on phase solubility studies and molecular modeling to prepare an inclusion complex of BDQ and cyclodextrin. Aqueous solubility of BDQ was increased by 2.8 × 103-fold after complexation with SBE-β-CD, as compared to its intrinsic solubility. Solid-state characterization studies confirmed the successful incorporation of BDQ in the SBE-β-CD cavity. In vitro lung deposition study results demonstrated excellent inhalable properties (mass median aerodynamic diameter: 2.9 ± 0.6 µm (<5 µm) and fine particle fraction: 83.3 ± 3.8%) of BDQ-CD complex. Accelerated stability studies showed BDQ-CD complex to be stable up to 3 weeks. From cytotoxicity studies, a slight enhancement in the anti-cancer efficacy was observed with BDQ-cyclodextrin complex, compared to BDQ alone in H1299 cell line. The IC50 values for BDQ and BDQ-CD complex were found to be ~40 µM in case of H1299 cell line at 72 h, whereas BDQ/BDQ-CD were not found to be cytotoxic up to concentrations of 50 µM in A549 cell line. Taken together, BDQ-CD complex offers a promising inhalation strategy with efficient lung deposition and cytotoxicity for NSCLC treatment.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Parvathaneni

Elbatanony

Goyal

et al. 2021

IJMS

Self Cite

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“…Thus, the risk of drug side effects can be reduced. There are some examples of biomaterials-based drug delivery systems in the literature that were applied in the treatment of several disorders such as lung cancer and influenza [178][179][180]. Drugencapsulating natural biodegradable polymers, including cyclodextrin, albumin, alginate, chitosan, gelatin, collagen, and synthetic polymers including polylactide (PLA), polyglycolide (PLGA), polyacrylates, and polyanhydrides are suitable for the development of pulmonary therapeutic molecule delivery systems [181,182].…”

Section: Theraputicsmentioning

confidence: 99%

Role of biomaterials in the diagnosis, prevention, treatment, and study of corona virus disease 2019 (COVID-19)

et al. 2021

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Recently emerged novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the resulting corona virus disease 2019 (COVID-19) led to urgent search for methods to prevent and treat COVID-19. Among important disciplines that were mobilized is the biomaterials science and engineering. Biomaterials offer a range of possibilities to develop disease models, protective, diagnostic, therapeutic, monitoring measures, and vaccines. Among the most important contributions made so far from this field are tissue engineering, organoids, and organ-on-a-chip systems, which have been the important frontiers in developing tissue models for viral infection studies. Also, due to low bioavailability and limited circulation time of conventional antiviral drugs, controlled and targeted drug delivery could be applied alternatively. Fortunately, at the time of writing this paper, we have two successful vaccines and new at-home detection platforms. In this paper, we aim to review recent advances of biomaterial-based platforms for protection, diagnosis, vaccination, therapeutics, and monitoring of SARS-CoV-2 and discuss challenges and possible future research directions in this field.

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Nanophytomedicine: A promising practical approach in phytotherapy

Sardarabadi,

Darvishi,

Zohrab

et al. 2024

Phytotherapy Research

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The long and rich history of herbal therapeutic nutrients is fascinating. It is incredible to think about how ancient civilizations used plants and herbs to treat various ailments and diseases. One group of bioactive phytochemicals that has gained significant attention recently is dietary polyphenols. These compounds are commonly found in a variety of fruits, vegetables, spices, nuts, drinks, legumes, and grains. Despite their incredible therapeutic properties, one challenge with polyphenols is their poor water solubility, stability, and bioavailability. This means that they are not easily absorbed by the body when consumed in essential diets. Because of structural complexity, polyphenols with high molecular weight cannot be absorbed in the small intestine and after arriving in the colon, they are metabolized by gut microbiota. However, researchers are constantly working on finding solutions to enhance the bioavailability and absorption of these compounds. This study aims to address this issue by applying nanotechnology approaches to overcome the challenges of the therapeutic application of dietary polyphenols. This combination of nanotechnology and phytochemicals could cause a completely new field called nanophytomedicine or herbal nanomedicine.

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Cyclodextrin Complexation for Enhanced Stability and Non-invasive Pulmonary Delivery of Resveratrol—Applications in Non-small Cell Lung Cancer Treatment

Cited by 34 publications

References 54 publications

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Repurposing Bedaquiline for Effective Non-Small Cell Lung Cancer (NSCLC) Therapy as Inhalable Cyclodextrin-Based Molecular Inclusion Complexes

Role of biomaterials in the diagnosis, prevention, treatment, and study of corona virus disease 2019 (COVID-19)

Nanophytomedicine: A promising practical approach in phytotherapy

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