Utilization of novel self-nanoemulsifying formulations (SNEFs) loaded paclitaxel for the treatment prosperity of bladder cancer

Qasem M A Abdallah, Mohsin Kazi, Mohammad A. Khaleel, Ibrahim Al-Deeb, Abdel-Rahman T. Nasr, Roger Phillips

Research output: Contribution to journalArticle

Abstract

Background
Limited drug penetration into solid tumors has been one of the potential causes of resistance to chemotherapy for the treatment of bladder cancer. The aim of the studies was to develop non-toxic nanoemulsion carriers of paclitaxel and to evaluate their ability to serve as a tool increasing and/or controlling the penetration of paclitaxel through the bladder tissue.

Methods
Various oil-in-water non-toxic self-nanoemulsifying formulations (SNEFs) were developed using Cremercoor MCT, Kollisolv MCT, Miglyol 812, 810, Capmul MCM, Imwitor 988, Imwitor 742 with TO106V, Tween 85, HCO30, Kolliphor EL and Cremophor RH40 at size ranges from approximately 19 to 110 nm that are capable of enhancing the solubility and stability of paclitaxel. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEFs. Paclitaxel was added with the oil/surfactant mixture before dispersing the mixture in water to form SNEF. The penetration study of the optimal SNEFs formulation was compared with the raw paclitaxel dispersion using transwell apparatus.

Results
Initial characterisation and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 with water-soluble surfactant (high HLB) containing formulations generated highly efficient SNEFs as they are stable and produced lower nanodroplets with higher drug loading. The results have demonstrated that the SNEFs have good ability to retain its characteristics under conditions similar to that found in the urinary bladder up to 48 h. However, the results also showed that chemosensitivity of cancer cells exposed to paclitaxel was attenuated in the presence of SNEFs. Larger size SNEFs have shown to induce more inhibitory effects on paclitaxel activity. The reduction effects of SNEFs on doxorubicin (a relatively water-soluble drug) efficacy were almost absent, indication a poor loading of such compounds.

Conclusion
The reduction of the efficacy of SNEF loaded treatments does not give a strong indication of their ability to penetrate as examined their ability to penetrate through the cultivated multicell layers (MCL) of bladder cancer. However, these results may open the horizon to reflect the use of SNEFs in the introduction of intravenous paclitaxel because of its potential role in reducing the injection site toxicity.
Original languageEnglish
Article number101514
JournalJournal of Drug Delivery Science and Technology
Early online date10 Jan 2020
DOIs
Publication statusE-pub ahead of print - 10 Jan 2020

Fingerprint

Paclitaxel
Urinary Bladder Neoplasms
Water
Therapeutics
Surface-Active Agents
Solubility
Oils
Urinary Bladder
Pharmaceutical Preparations
Glycerides
Polysorbates
Doxorubicin
Neoplasms
Drug Therapy
Injections

Cite this

@article{a861acbf278a44c8af73b3cb6f28058a,
title = "Utilization of novel self-nanoemulsifying formulations (SNEFs) loaded paclitaxel for the treatment prosperity of bladder cancer",
abstract = "BackgroundLimited drug penetration into solid tumors has been one of the potential causes of resistance to chemotherapy for the treatment of bladder cancer. The aim of the studies was to develop non-toxic nanoemulsion carriers of paclitaxel and to evaluate their ability to serve as a tool increasing and/or controlling the penetration of paclitaxel through the bladder tissue.MethodsVarious oil-in-water non-toxic self-nanoemulsifying formulations (SNEFs) were developed using Cremercoor MCT, Kollisolv MCT, Miglyol 812, 810, Capmul MCM, Imwitor 988, Imwitor 742 with TO106V, Tween 85, HCO30, Kolliphor EL and Cremophor RH40 at size ranges from approximately 19 to 110 nm that are capable of enhancing the solubility and stability of paclitaxel. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEFs. Paclitaxel was added with the oil/surfactant mixture before dispersing the mixture in water to form SNEF. The penetration study of the optimal SNEFs formulation was compared with the raw paclitaxel dispersion using transwell apparatus.ResultsInitial characterisation and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 with water-soluble surfactant (high HLB) containing formulations generated highly efficient SNEFs as they are stable and produced lower nanodroplets with higher drug loading. The results have demonstrated that the SNEFs have good ability to retain its characteristics under conditions similar to that found in the urinary bladder up to 48 h. However, the results also showed that chemosensitivity of cancer cells exposed to paclitaxel was attenuated in the presence of SNEFs. Larger size SNEFs have shown to induce more inhibitory effects on paclitaxel activity. The reduction effects of SNEFs on doxorubicin (a relatively water-soluble drug) efficacy were almost absent, indication a poor loading of such compounds.ConclusionThe reduction of the efficacy of SNEF loaded treatments does not give a strong indication of their ability to penetrate as examined their ability to penetrate through the cultivated multicell layers (MCL) of bladder cancer. However, these results may open the horizon to reflect the use of SNEFs in the introduction of intravenous paclitaxel because of its potential role in reducing the injection site toxicity.",
keywords = "Self-nanoemulsifying formulations, In vitro dispersion, Paclitaxel, Penetration, Bladder cancer",
author = "Abdallah, {Qasem M A} and Mohsin Kazi and Khaleel, {Mohammad A.} and Ibrahim Al-Deeb and Nasr, {Abdel-Rahman T.} and Roger Phillips",
year = "2020",
month = "1",
day = "10",
doi = "10.1016/j.jddst.2020.101514",
language = "English",
journal = "Journal of Drug Delivery Science and Technology",
issn = "1773-2247",
publisher = "Editions de Sante",

}

Utilization of novel self-nanoemulsifying formulations (SNEFs) loaded paclitaxel for the treatment prosperity of bladder cancer. / Abdallah, Qasem M A; Kazi, Mohsin; Khaleel, Mohammad A.; Al-Deeb, Ibrahim; Nasr, Abdel-Rahman T.; Phillips, Roger.

In: Journal of Drug Delivery Science and Technology, 10.01.2020.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Utilization of novel self-nanoemulsifying formulations (SNEFs) loaded paclitaxel for the treatment prosperity of bladder cancer

AU - Abdallah, Qasem M A

AU - Kazi, Mohsin

AU - Khaleel, Mohammad A.

AU - Al-Deeb, Ibrahim

AU - Nasr, Abdel-Rahman T.

AU - Phillips, Roger

PY - 2020/1/10

Y1 - 2020/1/10

N2 - BackgroundLimited drug penetration into solid tumors has been one of the potential causes of resistance to chemotherapy for the treatment of bladder cancer. The aim of the studies was to develop non-toxic nanoemulsion carriers of paclitaxel and to evaluate their ability to serve as a tool increasing and/or controlling the penetration of paclitaxel through the bladder tissue.MethodsVarious oil-in-water non-toxic self-nanoemulsifying formulations (SNEFs) were developed using Cremercoor MCT, Kollisolv MCT, Miglyol 812, 810, Capmul MCM, Imwitor 988, Imwitor 742 with TO106V, Tween 85, HCO30, Kolliphor EL and Cremophor RH40 at size ranges from approximately 19 to 110 nm that are capable of enhancing the solubility and stability of paclitaxel. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEFs. Paclitaxel was added with the oil/surfactant mixture before dispersing the mixture in water to form SNEF. The penetration study of the optimal SNEFs formulation was compared with the raw paclitaxel dispersion using transwell apparatus.ResultsInitial characterisation and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 with water-soluble surfactant (high HLB) containing formulations generated highly efficient SNEFs as they are stable and produced lower nanodroplets with higher drug loading. The results have demonstrated that the SNEFs have good ability to retain its characteristics under conditions similar to that found in the urinary bladder up to 48 h. However, the results also showed that chemosensitivity of cancer cells exposed to paclitaxel was attenuated in the presence of SNEFs. Larger size SNEFs have shown to induce more inhibitory effects on paclitaxel activity. The reduction effects of SNEFs on doxorubicin (a relatively water-soluble drug) efficacy were almost absent, indication a poor loading of such compounds.ConclusionThe reduction of the efficacy of SNEF loaded treatments does not give a strong indication of their ability to penetrate as examined their ability to penetrate through the cultivated multicell layers (MCL) of bladder cancer. However, these results may open the horizon to reflect the use of SNEFs in the introduction of intravenous paclitaxel because of its potential role in reducing the injection site toxicity.

AB - BackgroundLimited drug penetration into solid tumors has been one of the potential causes of resistance to chemotherapy for the treatment of bladder cancer. The aim of the studies was to develop non-toxic nanoemulsion carriers of paclitaxel and to evaluate their ability to serve as a tool increasing and/or controlling the penetration of paclitaxel through the bladder tissue.MethodsVarious oil-in-water non-toxic self-nanoemulsifying formulations (SNEFs) were developed using Cremercoor MCT, Kollisolv MCT, Miglyol 812, 810, Capmul MCM, Imwitor 988, Imwitor 742 with TO106V, Tween 85, HCO30, Kolliphor EL and Cremophor RH40 at size ranges from approximately 19 to 110 nm that are capable of enhancing the solubility and stability of paclitaxel. Visual assessment was employed and droplet size measurement was taken into initial consideration for optimized SNEFs. Paclitaxel was added with the oil/surfactant mixture before dispersing the mixture in water to form SNEF. The penetration study of the optimal SNEFs formulation was compared with the raw paclitaxel dispersion using transwell apparatus.ResultsInitial characterisation and solubility studies showed that mixed glycerides of Kollisolv MCT/Imwitor 742 with water-soluble surfactant (high HLB) containing formulations generated highly efficient SNEFs as they are stable and produced lower nanodroplets with higher drug loading. The results have demonstrated that the SNEFs have good ability to retain its characteristics under conditions similar to that found in the urinary bladder up to 48 h. However, the results also showed that chemosensitivity of cancer cells exposed to paclitaxel was attenuated in the presence of SNEFs. Larger size SNEFs have shown to induce more inhibitory effects on paclitaxel activity. The reduction effects of SNEFs on doxorubicin (a relatively water-soluble drug) efficacy were almost absent, indication a poor loading of such compounds.ConclusionThe reduction of the efficacy of SNEF loaded treatments does not give a strong indication of their ability to penetrate as examined their ability to penetrate through the cultivated multicell layers (MCL) of bladder cancer. However, these results may open the horizon to reflect the use of SNEFs in the introduction of intravenous paclitaxel because of its potential role in reducing the injection site toxicity.

KW - Self-nanoemulsifying formulations

KW - In vitro dispersion

KW - Paclitaxel

KW - Penetration

KW - Bladder cancer

U2 - 10.1016/j.jddst.2020.101514

DO - 10.1016/j.jddst.2020.101514

M3 - Article

JO - Journal of Drug Delivery Science and Technology

JF - Journal of Drug Delivery Science and Technology

SN - 1773-2247

M1 - 101514

ER -