Papers by Chukwunweike Okeke
Journal of Biomedical Nanotechnology
The combination of antiangiogenesis with chemotherapy has become a promising multi-modal combinat... more The combination of antiangiogenesis with chemotherapy has become a promising multi-modal combinational therapy for solid tumor. However, hypoxia-mediated resistance and the subsequent treatment failure associated with antiangiogenesis therapy have limited the maximization of this promising approach. It remains a major challenge to balance the effect of angiogenesis and the accumulation of the cytotoxic drug within the tumor microenvironment. In this study, we report a nanotechnology based drug delivery solution that would improve both the antiangiogenic activity and cytotoxic efficacy of the loaded drugs. We designed core–shell ‘lipid nanocells’ drug delivery systems (denoted as DTX/ITZ-LNCs), which entrapped the antiangiogenic drug itraconazole (ITZ) in the outside liposomal shell and encapsulated anticancer drug docetaxel (DTX) in the inner hydrophobic PLGA core. In vitro evaluations showed that the dual drug loaded DTX/ITZ-LNCs retained the cytotoxic efficacy of the DTX against both the sensitive and multidrug resistant breast cancer cell line MCF-7. DTX/ITZ-LNCs also effectively inhibited the vascular endothelial growth factor (VEGF) induced migratory and invasive actions of HUVECs and neovascularization of subcutaneously implanted matrigel plugs. The tumor growth of MCF-7 tumor xenograft model was effectively inhibited by the systemic administration of the DTX/ITZ-LNCs. Taken together, these results showed that the DTX/ITZ-LNCs provided a drug delivery platform that can optimize the combinatory effects of the antiangiogenic agent with a conventional chemotherapeutic agent.
Nano Research
Seeking profitable therapies for triple-negative breast cancer (TNBC) has attracted intense resea... more Seeking profitable therapies for triple-negative breast cancer (TNBC) has attracted intense research interest. However, an efficient cure for TNBC remains an unresolved challenge in oncology. Herein, for the first time, we describe the use of polymeric nanoparticles loaded with NVP-BEZ235 and Chlorin-e6, denoted as NVP/Ce6@NPs, to overcome the adaptive treatment tolerance of TNBC by taking advantage of the synergistic effect between biochemical and photodynamic therapies. Upon laser irradiation, the NVP/Ce6@NPs generated reactive oxygen species (ROS) and efficiently induced the apoptosis of tumor cells through DNA damage. Furthermore, the released NVP-BEZ235 could prevent Chk1 phosphorylation-induced DNA damage repair, thus enhancing the sensitivity of tumor cells to ROS. Animal studies on mice bearing an MDA- MB-231 tumor validated that the NVP/Ce6@NPs had a greater therapeutic efficacy compared to that of monotherapies, with an inhibition ratio of 89.3%. Western blotting and cell viability analyses confirmed the inhibition of both MDA-MB-231 cell proliferation and Chk1 phosphorylation by NVP/Ce6@NPs. These findings provide a rational understanding of the synergistic effect of the biochemical/photodynamic therapy and pave the way for the development of efficient therapeutic approaches to fight against TNBC.
RSC Adv.
pH-sensitive polymeric micelles for targeted co-delivery of mitochondria-damaged proapoptotic pep... more pH-sensitive polymeric micelles for targeted co-delivery of mitochondria-damaged proapoptotic peptide and DTX for synergistic cancer therapy.
Current pharmaceutical design, Jan 17, 2016
Polymersomes are self-assembled nano-vesicles composed of amphiphilic block copolymers. These bui... more Polymersomes are self-assembled nano-vesicles composed of amphiphilic block copolymers. These building blocks can be selected from a large number of hydrophilic and hydrophobic polymers in order to achieve required properties of the final system, such as biodegradability, sustainable and multiple stimuli-response drug release, long blood circulation, and low toxicity. Moreover, the surface of polymersomes can be functionalized to induce targeted character. Polymersomes are able to encapsulate a broad range of hydrophilic or/and hydrophobic molecules either in the aqueous core or membrane bilayer, respectively. In addition, colloidal stability and low membrane fluidity make polymersomes attractive nano-sized drug carriers. The review describes polymersomes compositions, their applications in pharmaceutical delivery, and preparation methods.
ACS applied materials & interfaces, Jan 19, 2015
Carrier-free pure nanodrugs (PNDs) that are composed entirely of pharmaceutically active molecule... more Carrier-free pure nanodrugs (PNDs) that are composed entirely of pharmaceutically active molecules are regarded as promising candidates to be the next generation of drug formulations and are mainly formulated from supramolecular self-assembly of drug molecules. It benefits from the efficient use of drug compounds with poor aqueous solubility and takes advantage of nanoscale drug delivery systems. Here, a type of all-in-one nanoparticle consisting of multiple drugs with enhanced synergistic antiproliferation efficiency against drug-resistant cancer cells has been created. To nanoparticulate the anticancer drugs, 10-hydroxycamptothecin (HCPT) and doxorubicin (DOX) were chosen as a typical model. The resulting HD nanoparticles (HD NPs) were formulated by a "green" and convenient self-assembling method, and the water-solubility of 10-hydroxycamptothecin (HCPT) was improved 50-fold after nanosizing by coassembly with DOX. The formation process was studied by observing the morph...
Objective To apply the response surface-central composite design to developing and optimizing the... more Objective To apply the response surface-central composite design to developing and optimizing the oral fast disintegrating tablets (ODT) formulation for Jiawei Qing'e, a kind of prescription of Chinese herbal medicine.Methods The bitterness of Jiawei Qing'e was masked using Eudragit E-100 by solvent evaporation technique. Response surface approach was applied to investigating the interaction of formulation parameters in optimizing the formulation. The independent variables were Eudragit E-100/drug ratio (X1), amount of disintegrants (X2), and the amount of diluents (X3). The disintegration time (Y1), hardness (Y2), and weight variations of the tablets were characterized.ResultsThe models predicted levels of X1 = 4.63%, X2 = 5.25%, and X3 = 34.33%, for the optimal formulation having a hardness of 3.0 kg with the disintegration time of 30 s within experimental region. The observed response of Y1 = 26.5 s and Y2 = 3.14 kg reasonably agreed with the predicted response.Conclusion...
International journal of pharmaceutics, Jan 17, 2015
Baicalin has many pharmacological activities, including neuroprotective function against ischemia... more Baicalin has many pharmacological activities, including neuroprotective function against ischemia and neurodegeneration. In our previous study, we found that Baicalin-loaded PEGylated cationic solid lipid nanoparticles modified by OX26 antibody (OX26-PEG-CSLN) might be a promising carrier to deliver drugs across the blood-brain barrier for the treatment of brain diseases. So, the aim of this present study was to further elucidate the mechanisms of OX26-PEG-CSLN cerebral ischemia protection by monitoring the changes of extracellular amino acids. In addition, we investigated the effect of OX26-PEG-CSLN on the excitotoxic neuronal injury as well as the pharmacokinetic profiles of baicalin in cerebrospinal fluid during ischemia-reperfusion period. The cerebrospinal fluid was collected by a microdialysis technique and divided into two parts-one part for pharmacokinetic study of baicalin using LC-MS/MS method and the other for pharmacodynamic study which was done by pre-column derivatizat...
Current Pharmaceutical Design, 2015
1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE- PEG) is a widely us... more 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE- PEG) is a widely used phospholipids-polymer conjugate in drug delivery applications. It is a biocompatible, biodegradable and amphiphilic material which can also be functionalized with various biomolecules for specific functions. With the emerging interest in use of nanocarriers for therapeutic drug delivery and imaging DSPE-PEG has become a very useful material for the formulation of these nanocarriers for achieving prolonged blood circulation time, improved stability and enhanced encapsulation efficiency. This review will focus on the relationships between the structure of DSPEPEG and its noticeable effects on these nanocarriers' properties, and the recent progress on the development of DSPE-PEG and its derivatives in delivery systems.
Current pharmaceutical design, 2015
1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE- PEG) is a widely us... more 1, 2-Distearoyl-sn-glycero-3-phosphoethanolamine-Poly(ethylene glycol) (DSPE- PEG) is a widely used phospholipids-polymer conjugate in drug delivery applications. It is a biocompatible, biodegradable and amphiphilic material which can also be functionalized with various biomolecules for specific functions. With the emerging interest in use of nanocarriers for therapeutic drug delivery and imaging DSPE-PEG has become a very useful material for the formulation of these nanocarriers for achieving prolonged blood circulation time, improved stability and enhanced encapsulation efficiency. This review will focus on the relationships between the structure of DSPEPEG and its noticeable effects on these nanocarriers' properties, and the recent progress on the development of DSPE-PEG and its derivatives in delivery systems.
Drug development and industrial pharmacy, 2013
International journal of pharmaceutics, 2013
Available online xxx Keywords: Ofloxacin Ophthalmic in situ gel Systemic absorption HPLC-MS/MS a ... more Available online xxx Keywords: Ofloxacin Ophthalmic in situ gel Systemic absorption HPLC-MS/MS a b s t r a c t
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Papers by Chukwunweike Okeke