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RESEARCH |
Chemotherapeutic Engineering – Application and further development of chemical engineering principles to solve problems in chemotherapy of cancer and other diseases such as cardiovascular restenosis and AIDS.
Cancer is a leading cause of deaths and is becoming the #1 killer in many countries including Singapore. Although great effort has been made, no substantial progress can be observed in the past 50 years in the fight against cancer. The cancer death rate in US was 1.939 ‰ of the total population in 1950. It is still 1.940‰ in 2001, 1.934‰ in 2002, and 1.930‰ in 2003. Nanomedicine - Cancer Nanotechnology - Chemotherapeutic Engineering will radically change the very foundations of cancer diagnosis, treatment and prevention. The current regimen of chemotherapy is far from being satisfactory. Its efficacy is limited and patients have to suffer from severe side effects. We have obtained through a full spectrum of research the proof-of-concept results to demonstrate how nanoparticle technology could provide an ideal solution for the problems encountered in current regimen of chemotherapy and with further development, promote New-Concept of Chemotherapy, which may include sustained, controlled and targeted chemotherapy; personalized chemotherapy; chemotherapy across various physiological drug barriers; and eventually, Chemotherapy at Home. We have shown that paclitaxel-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles could be 5.64 times more effective than that for Taxol® after 24 hour culture will HT-29 cells (a colon cancer cell line) at the same drug concentration. In vivo pharmacokinetics measurements confirmed the advantages of the nanoparticle formulation versus Taxol®. The plasma concentration of the nanoparticle formulation had an area-under-the-curve (AUC) value comparable with that of Taxol®, but never exceeded the maximum tolerance level and hence should have much lesser side effects than Taxol®. The nanoparticle formulation had a sustainable therapeutic time of 168 hours in comparison with 22 hours for Taxol® and achieved four times greater drug tolerance than Taxol®. Targeted chemotherapy by HER2 or Folate decorated nanoparticles are underdevelopment. High attention has been paid to safety issue and mechanism of toxicity casued by nanotechnology is being investigated. It seems to us that our PLA-TPGS nanoparticles can provide an ideal solution.
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On-going research in The Chemotherapeutic Engineering Laboratory:
- Advanced biomaterials: Synthesis of biodegradable copolymers of desired hydrophobic-lipophilic balance (HLB) for biomedical applications;
- Novel prodrugs: Polymeric conjugation of anticancer drugs for better solubility, permeability and stability;
- Oral chemotherapy: a key step towards “chemotherapy at home” to improve the quality of life of the patients；
- NanoTaxanes®: Nanoparticle formulation of anticancer drugs which devoid of harmful adjuvant such as Cremophor EL in Taxol® and Polysobate 80 in Taxotere®;
- NanoIOs® & NanoQDs®: Formulation of iron oxides (IOs) and quantum dots (QDs) by polymeric nanoparticles of molecular probe decoration for molecular imaging;
- NanoStents®: Nanoparticles for cardiovascular tissue repair, the 3rd generation of stents;
- Nanoparticles for gene therapy;
- Nanotechnology for aging diseases: Drug delivery across the blood-brain barrier (BBB).
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Lipid Monolayer-Bilayer Correspondence
The lipid monolayer-bilayer correspondence problem has aroused continuous interest in the past few decades. Lipid bilayer is a key component of the biological membrane. Lipid bilayer vesicles (liposomes) have wide applications in drug delivery, biosensors, gene therapy and artificial blood. Liposomes are difficult to manipulate in experiment. Instead, measurement of the lipid monolayer at the air-water or oil-water interface can be easily done under various conditions. The problem is how we can obtain bilayer properties from the monolayer measurement. A theory has been developed to solve this problem, which is of basic importance in simulation of liposomes and biomembranes by the monolayer as well as in investigation of molecular interactions between the cell membrane and the drug molecules. For latest progress, see: Feng SS, Langmuir 1999; 2006.
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Editorial Board Members:
- Biomaterials (Associate Editor)
- Nanomedicine
- Int’l J of Nanomedicine
- J Biomedical Nanotechnology
- Int’l J Med Engi & Info
- Recent Patent Drug Del Formulation
- Chinese J Biomed Eng
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Founding Articles:
- Feng SS. Biomaterials, 29(30):4146-4147, Oct 2008 (the first-ever SnapShot of the Journal).
- Feng SS, Zhao LY, Zhang ZP, Bhakta G, Win KY, Dong YC, Chien S. Chem Eng Sci, 62:6641-6648, Dec 2007
- Feng SS, Zeng WT, Zhao LY, Lim YT, Oaklay R, Teoh SH, Lee CHR, Pan SR. Nanomedicine 2(3):333-344, 2007.
- Feng SS. Nanomedicine, 1(3):297-309, 2006.
- Feng SS. Chemotherapy, Expert Review Med Dev 1(1):115-125, 2004.
- Feng SS, Chien S. Chem Eng Sci 58:4087-4114, 2003.
- Feng SS, Mu L, Win KY, Huang GF. Curr Med Chem. 11:413-424, 2004.
- Feng SS. Langmuir, 15(4), 998-1010, 1999, also, 22:2920-2922, 2006.
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SELECTED PUBLICATIONS
(6 papers in US NCI’s "Nanotechnology in Cancer" website and 13 papers ranked by ScienceDirect as Top 25 Hottest Papers) |
Pan J, Feng SS. Targeting and imaging cancer cells by folate decorated, "quantum dots loaded nanoparticles of biodegradable polymers". Biomaterials 30:1176–1183, 2009. |
Zhang ZP, Lee SH, Gan CW, Feng SS. Pharmacokinetics, "Biodistribution and Xenograft Tumor Model of PLA-TPGS Nanoparticles Prepared by Dialysis Method for Controlled and Sustained Small Molecule Chemotherapy". Pharmaceutical Research, 25(8):1925-1935, 2008. |
Cao N, Feng SS. "Doxorubicin Conjugated to d-α-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS): In vitro Cytotoxicity, In vivo Pharmacokinetics and Biodistribution". Biomaterials, 29(28):3856–3865, 2008. |
Pan J, Feng SS. "Folate-decorated poly (lactide)-vitamin E TPGS nanoparticles for targeted delivery of paclitaxel", Biomaterials, 29:2663-2672, 2008. |
Sun BF, Ranganathan B, Feng SS. "Multi-functional poly(D,L-lactide-co-glycolide)/ montmorillonite (PLGA/MMT) nanoparticles decorated by Trastuzumab for targeted chemotherapy of breast cancer". Biomaterials, 29:475–486, 2008. |
Wang Y, Ng YW, Chen Y, Shuter B, Yi JB, Ding J, Wang SC, Feng SS. "Formulation of Superparamagnetic Iron Oxides (IOs). by Nanoparticles of Biodegradable Polymers for Magnetic Resonance Imaging (MRI)". Advanced Functional Materials, 18(2):308-318, 2008. |
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