Pluronic-PEI Micelles Reverse Multidrug Resistance by Depleting ATP and Inhibiting P-Glycoprotein for Colon Cancer Therapy

2017 ◽  
Vol 886 ◽  
pp. 111-116 ◽  
Author(s):  
He Bin Wang ◽  
Yang Li ◽  
Kai Hang Liu ◽  
Jun Zhou ◽  
Gu Ping Tang
Keyword(s):  
Drug Loading ◽  
In Vivo Studies ◽  
Tumor Cell Apoptosis ◽  
Serum Stability ◽  
Promising Strategy ◽  
P Glycoprotein ◽  
Growth Of Tumor ◽  
High Drug Loading

We have designed a polymer micelles based on Pluronic P123 and Polyethyleneimine 600 (termed as P123P600). Upon critical micelle concentration the P123P600 unimer formed micelles in water. These micelles not only could simultaneously delivery hydrophobic anticancer drug paclitaxel (PTX) to cancer cells but also could deplete ATP and inhibit P-gp expression in MDR cells. In vitro researches demonstrated that these micelles showed the excellent biocompatibility, high drug loading efficiency, stably controlled releasing behavior, enhanced cellular up-take and improved serum stability. In vivo studies demonstrated that the PTX loaded micelles induced tumor cell apoptosis and inhibited the growth of tumor to overcome drug resistance through a synergistic effect. All these findings suggested that P123P600 for delivery of anticarcinogen provided a promising strategy for reversal of MDR in cancer treatment.

Effects of Polyoxyethylene Alkyl Ethers on the Intestinal Transport and Absorption of Rhodamine 123: A P-glycoprotein Substrate by In Vitro and In Vivo Studies

2016 ◽  
Vol 105 (4) ◽  
pp. 1526-1534 ◽  
Author(s):  
Wanting Zhao ◽  
Sachiyo Uehera ◽  
Keiichiro Tanaka ◽  
Shuhei Tadokoro ◽  
Kosuke Kusamori ◽  
...  
Keyword(s):  
Intestinal Transport ◽  
Rhodamine 123 ◽  
In Vivo Studies ◽  
P Glycoprotein ◽  
Alkyl Ethers

Pharmacokinetic Profile of Oxaliplatin-Loaded pH-Responsive Hydrogels in Rabbits

2020 ◽  
Vol 26 (44) ◽  
pp. 5755-5763
Author(s):  
Kaleem Ullah ◽  
Shujaat Ali Khan ◽  
Muhammad Sohail ◽  
Abdul Mannan ◽  
Ghulam Murtaza
Keyword(s):  
Drug Release ◽  
Drug Loading ◽  
Oral Solution ◽  
In Vivo Studies ◽  
Pharmacokinetic Parameters ◽  
Platinum Compound ◽  
In Vivo Evaluation ◽  
Significant Difference

Background: Oxaliplatin (OXP), a 3rd generation platinum compound, which causes severe side effects due to; impulse high concentration in the bloodstream thereby exposing healthy cells at a high ratio, nonspecific delivery at the target site and non-compliance is administered intravenously. Objective: The project was aimed at the development, characterization, and in-vitro and in-vivo evaluation of pHresponsive hydrogels for oral administration of OXP. Methods: Hydrogel formulations were synthesized through a free radical polymerization technique followed by brief characterization using various techniques. The hydrogels were investigated for various in-vitro studies such as sol-gel, drug loading, swelling, drug release, and MTT-assay. While in-vivo studies such as oral tolerability, histopathology, and hematology studies were performed on rabbits. A simple and sensitive HPLC-UV method was optimized and the comparative pharmacokinetic study was performed in rabbits using OXP-oral solution and OXP-loaded hydrogels. Results: In-vitro characterization confirmed that the reactant was successfully crosslinked to form thermally stable hydrogels with decreased crystallinity and rough surface. Swelling and drug release showed that hydrogels were more responsive to basic pH (6.8 and 7.4) in comparison with pH 1.2. The blank hydrogels were cytocompatible as more than 95% of the cells were viable while free OXP and OXP-loaded hydrogels displayed dosedependent cytotoxic effect. In-vivo studies confirmed that chitosan and gelatin hydrogel suspension was well tolerable up to 3800 mg/kg and 4000 mg/kg of body weight, respectively. Hematology and serum chemistry reports were well within the range suggesting normal liver and kidney functions. Similarly, histopathology slides of rabbit vital organs were also found normal without causing any histopathological change. Conclusion: HPLC-UV method was successfully optimized for OXP detection in oral solution and hydrogels administered to rabbits. A significant difference was found among various pharmacokinetic parameters by comparing the two groups including half-life (t1/2), tmax, Cmax, AUCtot MRT, Vz, and Lz.

FORMULATION AND EVALUATION OF MICROSPHERES FOR NASAL DELIVERY OF ANTI-HYPERTENSIVE DRUG

INDIAN DRUGS ◽  
2016 ◽  
Vol 53 (10) ◽  
pp. 21-26
Author(s):  
S. S Shelake ◽  
◽  
R. M Mhetre ◽  
S. V Patil ◽  
S. S Patil ◽  
...  
Keyword(s):  
Drug Release ◽  
Ex Vivo ◽  
Drug Loading ◽  
Entrapment Efficiency ◽  
Nasal Delivery ◽  
In Vivo Studies ◽  
Oral Drug ◽  
Hypertensive Drug

Lisinopril is used in the treatment of hypertension and heart failure in myocardial infarction and also in diabetic nephropathy. It is very poorly absorbed from GIT. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The microspheres prepared by emulsion solvent evaporation method were characterized for encapsulation efficiency, drug loading, particle size, surface morphology, degree of swelling, ex vivo mucoadhesion, drug release and ex vivo diffusion studies. Entrapment efficiency of microspheres was in range of 84.95±0.50% to 97.44±0.61% mucoadhesion was 83.76% and 94.41% and drug release up to 40 minutes was 53.66% to 88.32%. In ex vivo studies, the microspheres showed good bioavailability by nasal route compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres are better than single carbopol-based formulation for the delivery of lisinopril.

scholarly journals A novel preparative method for nanoparticle albumin-bound paclitaxel with high drug loading and its evaluation both in vitro and in vivo

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250670
Author(s):  
Yue Gao ◽  
Jingxue Nai ◽  
Zhenbo Yang ◽  
Jinbang Zhang ◽  
Siyu Ma ◽  
...  
Keyword(s):  
Self Assembly ◽  
Drug Loading ◽  
Preparative Method ◽  
X Ray Diffraction ◽  
Scanning Calorimetry ◽  
Spectra Analysis ◽  
High Drug ◽  
High Drug Loading

We developed a novel preparative method for nanoparticle albumin-bound (nab) paclitaxel with high drug loading, which was based on improved paclitaxel solubility in polyethylene glycol (PEG) and self-assembly of paclitaxel in PEG with albumin powders into nanoparticles. That is, paclitaxel and PEG were firstly dissolved in ethanol, which was subsequently evaporated under vacuum. The obtained liquid was then mixed with human serum albumin powders. Thereafter, the mixtures were added into phosphate-buffered saline and nab paclitaxel suspensions emerged after ultrasound. Nab paclitaxel was finally acquired after dialysis and freeze drying. The drug loading of about 15% (W/V) were realized in self-made nab paclitaxel, which was increased by approximately 50% compared to 10% (W/V) in Abraxane. Now this new preparative method has been authorized to obtain patent from China and Japan. The similar characteristics of self-made nab paclitaxel compared to Abraxane were observed in morphology, encapsulation efficiency, in vitro release, X-ray diffraction analysis, differential scanning calorimetry analysis, and circular dichroism spectra analysis. Consistent concentration-time curves in rats, biodistributions in mice, anti-tumor activities in mice, and histological transmutation in mice were also found between Abraxane and self-made nanoparticles. In a word, our novel preparative method for nab paclitaxel can significantly improve drug loading, obviously decrease product cost, and is considered to have potent practical value.

Polyphenol-Based Paclitaxel Prodrug Self-Assembled Nanoplatform for Tumor Synergistic Therapy

2021 ◽  
Vol 17 (11) ◽  
pp. 2198-2209
Author(s):  
Guoqiang Rong ◽  
Maomao Xu ◽  
Suxin Shi ◽  
Quanjun Yao ◽  
Wei Cheng ◽  
...  
Keyword(s):  
Drug Loading ◽  
Clinical Applications ◽  
Enhanced Permeability And Retention ◽  
Therapy Effect ◽  
Low Toxicity ◽  
Self Assembled ◽  
Tumor Accumulation ◽  
High Drug Loading

With the development of nanomedicine, studies focus on self-assembled nanoplatforms to reduce the toxicity of paclitaxel (PTX), promote the immune function at low-toxicity PTX, and achieve tumor synergistic therapy. Herein, a new nanoplatform was prepared with self-assembled 5-hydroxydopamine (DA)-PTX@tannic acid (TA)-Fe3+ nanoparticles (TDPP NPs) by consolidation of targeted DA-PTX and TA with the assistance of coordination between polyphenols and Fe3+. The polyphenol-based TDPP NPs can reduce the toxicity of PTX and thereby realize the in vitro and in vivo synergistic effect against tumors. The low-toxicity TDPP NPs can enhance the expression of CD40 immune protein. Moreover, the TDPP NPs possessed a small size (52.2±4 nm), high drug loading efficiency (95%), and stable pharmacokinetics, ensuring high tumor accumulation of TDPP NPs by enhanced permeability and retention effect. Our work sheds new light on the nanoformulation of PTX with low toxicity and synergistic therapy effect, which may find clinical applications in the future.

scholarly journals Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

2020 ◽  
Author(s):  
Wenjun Jiang ◽  
Jiyuan Chen ◽  
Chunai Gong ◽  
Yuanyuan Wang ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Graphene Oxide ◽  
Drug Loading ◽  
Electron Interaction ◽  
Castration Resistant Prostate Cancer ◽  
High Drug ◽  
Castration Resistant ◽  
High Drug Loading

Abstract Background: Enzalutamide (Enz) has shown limited bioavailability via oral administration. It is easy for patients to develop into castration-resistant prostate cancer (CRPC) due to resistance to 18-24 months of androgen deprivation therapy (ADT). Moreover, it is hard to delivery Enz in vivo for low drug loading (DL) and encapsulation efficiency (EE).Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for castration-resistant prostate cancer (CRPC) intravenous treatment, with high drug loading efficiency.Methods: Aminated graphene quantum dots (GQDs) were first cross-linked via disulfide bonds into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study.Results: The results showed that high drug-loading efficiency was achieved by TP-GQDss via π-π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could promote the inhibition of cell growth in vitro against CRPC cells. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo. Conclusions: The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as an intravenous therapy platform for CRPC.

scholarly journals Intravenous delivery of enzalutamide based on high drug loading multifunctional graphene oxide nanoparticles for castration-resistant prostate cancer therapy

2019 ◽  
Author(s):  
Wenjun Jiang ◽  
Jiyuan Chen ◽  
Chunai Gong ◽  
Yuanyuan Wang ◽  
Yuan Gao ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Graphene Oxide ◽  
Drug Loading ◽  
Castration Resistant Prostate Cancer ◽  
High Drug ◽  
Castration Resistant ◽  
Drug Loading Efficiency ◽  
High Drug Loading

Abstract Background: Enzalutamide (Enz) has shown limited bioavailability via oral administration and is easy for patients to develop into castration-resistant prostate cancer (CRPC) due to resistance to 18-24 months of androgen deprivation therapy (ADT). Moreover, it is hard to delivery Enz for low drug loading (DL) and encapsulation efficiency (EE). Therefore, we developed a multifunctional enzalutamide-loaded graphene oxide nanosystem (TP-GQDss/Enz) for castration-resistant prostate cancer (CRPC) intravenous treatment, with high drug loading efficiency and good biocompatibility.Methods: Aminated graphene quantum dots (GQDs) were first cross-linked via a disulfide bond into a graphene quantum dot derivative of approximately 200 nm (GQDss), which was further functionalized with a tumour-targeting peptide and PEG to form TP-GQDss. Enz was loaded into TP-GQDss for in vitro and in vivo study.Results: The results showed that high drug-loading efficiency was achieved by TP-GQDss via π-π electron interaction. TP-GQDss could be rapidly internalized by CRPC cells via endocytosis. Moreover, Enz in TP-GQDss could promote the inhibition of cell growth in vitro against CRPC cells, while TP-GQDss alone did not show any obvious cytotoxicity on CRPC cells after 24 h of incubation. Further, TP-GQDss exhibited an enhanced cancer-targeting ability and alleviated the side effects of Enz in vivo. Conclusions: The multifunctional nanocarrier constructed here could accomplish controlled Enz release and serve as a intravenous therapy platform for CRPC.

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