Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy

Luo, Cong; Sun, Jin; Du, Yuqian; Zhang, He

doi:10.1016/j.jconrel.2013.12.030

Cited by 64 publications

(45 citation statements)

References 134 publications

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“…However most anticancer drugs are not good candidates for oral delivery owing to their low absorption in the gastrointestinal tract (GI) and as a result exhibit low oral bioavailability [ 8 – 9 ]. In order to develop an effective oral chemotherapy, the bioavailability of anticancer drugs should be improved [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

Ünal¹,

Öztürk²,

Bilensoy³

2015

Beilstein J. Org. Chem.

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Summary Background: The aim of this study was to design and evaluate hybrid cyclodextrin (CD) nanocapsules intended for the oral delivery of the anticancer agent camptothecin (CPT) in order to maintain drug stability in the body and to improve its eventual bioavailability. For this reason, an amphiphilic cyclodextrin (CD) derivative per-modified on the primary face 6OCAPRO was used as core molecule to form nanocapsules with the nanoprecipitation technique. Nanocapsules were further coated with the cationic polymer chitosan to improve the cellular uptake and interaction with biological membranes through positive surface charge. Nanocapsules were evaluated for their in vitro characteristics such as particle size, zeta potential, drug loading and release profiles followed by cell culture studies with the MCF-7 and Caco-2 cell line evaluating their anticancer efficacy and permeability. The CD nanocapsules were imaged by scanning electron microscopy (SEM). The concentration of CPT entrapped in nanocapsules was determined by reversed phase HPLC. The in vitro release study of CPT was performed with a dialysis bag method under sink conditions mimicking the gastric and intestinal pH. The hydrolytic stability of CPT in nanocapsules was investigated in simulated gastric and intestinal fluids (SGF, SIF). Results: The mean particle sizes of both anionic and cationic CPT-loaded nanocapsules were in the range of 180–200 nm with polydispersity indices lower than 0.400 indicating monodisperse size distribution of nanocapsules with favourable potential for intracellular drug delivery to tumour cells. Surface charges of anionic and cationic nanocapsules were demonstrated as −21 mV and +18 mV, respectively. The stability of CPT in simulated release media, SGF and SIF were maintained suggesting the improved protection of the drug molecule from rapid hydrolysis degradation or gastrointestinal pH in nanocapsule oily core. Furthermore CD nanocapsules showed higher anticancer efficacy than CPT solution against the MCF-7 cell line. Permeation of CPT across Caco-2 cells was found to be 3 fold higher when incorporated in hybrid CD nanocapsules compared with a DMSO solution. Conclusion: Oral CD nanocapsules indicating increased oral bioavailability might be a promising strategy to maintain the physiological stability and to improve the oral bioavailability of problematic anticancer drugs such as CPT which may contribute to patient quality of life and drug efficacy in cancer therapy.

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Section: Introductionmentioning

confidence: 99%

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

Ünal¹,

Öztürk²,

Bilensoy³

2015

Beilstein J. Org. Chem.

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“…The intravenous-to-oral switch in chemotherapy is recommended in our recent review due to its innate patient compliance and mild sustained drug concentration in the circulation. 45 At present, more than 60% of marketed drugs are administered via the oral route, 46 but approximately 70% of new chemical entities exhibit poor In situ single-pass perfusion, K a and P app of duodenum, jejunum, ileum, and colon (n = 6 for each group). (B) The inhibition of P-gp efflux test in ileum segment.…”

Section: ■ Discussionmentioning

confidence: 99%

Enteric Polymer Based on pH-Responsive Aliphatic Polycarbonate Functionalized with Vitamin E To Facilitate Oral Delivery of Tacrolimus

et al. 2015

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To improve the bioavailability of orally administered drugs, we synthesized a pH-sensitive polymer (poly(ethylene glycol)-poly(2-methyl-2-carboxyl-propylene carbonate)-vitamin E, mPEG-PCC-VE) attempting to integrate the advantages of enteric coating and P-glycoprotein (P-gp) inhibition. The aliphatic polycarbonate chain was functionalized with carboxyl groups and vitamin E via postpolymerization modification. Optimized by comparison and central composite design, mPEG113-PCC32-VE4 exhibited low critical micelle concentration of 1.7 × 10(-6) mg/mL and high drug loading ability for tacrolimus (21.2% ± 2.7%, w/w). The pH-responsive profile was demonstrated by pH-dependent swelling and in vitro drug release. Less than 4.0% tacrolimus was released under simulated gastric fluid after 2.5 h, whereas an immediate release was observed under simulated intestinal fluid. The mPEG113-PCC32-VE4 micelles significantly increased the absorption of P-gp substrate tacrolimus in the whole intestine. The oral bioavailability of tacrolimus micelles was 6-fold higher than that of tacrolimus solution in rats. This enteric polymer therefore has the potential to become a useful nanoscale carrier for oral delivery of drugs.

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“…In general, these multifunctional nanocarriers have potential to improve the therapeutic index by targeting multiple pathways, minimizing systematic toxicity by reducing the leakage of the chemotherapeutic drug in blood circulation, and delivering the chemotherapeutic drugs specifically to the tumor (Jin et al, 2012 ). More recent evidence in the progress of hybrid nanocarriers encompasses the integration of imaging capability (either attached on the surface of these hybrids or incorporated into their internal domains) for either pre-operative or post-operative diagnosis of tumor, or facilitate pharmacokinetic and pharmacodynamics studies as a part of drug delivery applications responsible to minimize drug cytotoxicity in normal tissues (Prakash et al, 2011 ; Hu et al, 2013 ; Luo et al, 2014 ; Song E. et al, 2014 ; Zeng et al, 2014 ; Wang et al, 2016 ). In brief, these hybrid nanocarriers hold tremendous potential to overcome the limitation of traditional chemotherapy (e.g., rapid clearance, high toxicity, and non-specific cell/tissue distribution; Wakaskar, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Cerasomes and Bicelles: Hybrid Bilayered Nanostructures With Silica-Like Surface in Cancer Theranostics

2018

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Over years, theranostic nanoplatforms have provided a new avenue for the diagnosis and treatment of various cancer types. To this end, a myriad of nanocarriers such as polymeric micelles, liposomes, and inorganic nanoparticles (NPs) with distinct physiochemical and biological properties are routinely investigated for preclinical and clinical studies. So far, liposomes have received great attention for various biomedical applications, however, it still suffers from insufficient morphological stability. On the other hand, inorganic NPs depicting excellent therapeutic ability have failed to address biocompatibility issues. This has raised a serious concern about the clinical approval of multifunctional organic or inorganic-based theranostic agents. Recently, partially silica coated nanohybrids such as cerasomes and bicelles demonstrating both diagnostic and therapeutic ability in a single system, have drawn profound attention as a fascinating novel drug delivery system. Compared with traditional liposomal or inorganic-based nanoformulations, this new and highly stable nanocarriers integrates the functional attributes of biomimetic liposomes and silica NPs, therefore, synergize strengths and functions, or even surpass weaknesses of individual components. This review at its best enlightens the emerging concept of such partially silica coated nanohybrids, fabrication strategies, and theranostic opportunities to combat cancer and related diseases.

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Emerging integrated nanohybrid drug delivery systems to facilitate the intravenous-to-oral switch in cancer chemotherapy

Cited by 64 publications

References 134 publications

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

Formulation development, stability and anticancer efficacy of core-shell cyclodextrin nanocapsules for oral chemotherapy with camptothecin

Enteric Polymer Based on pH-Responsive Aliphatic Polycarbonate Functionalized with Vitamin E To Facilitate Oral Delivery of Tacrolimus

Cerasomes and Bicelles: Hybrid Bilayered Nanostructures With Silica-Like Surface in Cancer Theranostics

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