NanocellNanocell

• Intro of Drug DeliveryIntro of Drug Delivery SystemSystem• What is nanocellWhat is nanocell• Marketing Marketing • EthicsEthics• MechanismMechanism Ms. SorayaMs. Soraya • SynthesisSynthesis Ms. TitimaMs. Titima• In vivo In vitroIn vivo In vitro Dr. PantheeDr. Panthee • Clinical trialClinical trial• SummarySummary

Ms. ChanokkamonMs. Chanokkamon

Dr. BonduushDr. Bonduush

Nanocell:Nanocell:

Introduction, Marketing part Introduction, Marketing part

and Ethical issuesand Ethical issues

Ms Chanokkamon CheawtadaMs Chanokkamon Cheawtada

Inter-U program AITInter-U program AIT

Scope: Marketing and EthicsScope: Marketing and Ethics• Drug delivery systemDrug delivery system

– General cancerGeneral cancer

• Liver cancer treatmentLiver cancer treatment• Conventional drug for treat liver cancerConventional drug for treat liver cancer• Problems of conventional drugProblems of conventional drug• What is “nanocell”?What is “nanocell”?• Advantage of nanocellAdvantage of nanocell• Compare cost-benefit between conventional drug Compare cost-benefit between conventional drug

and nanocelland nanocell• Using Calculation for profit cost for developing Using Calculation for profit cost for developing

country (Ethics)country (Ethics)

Drug delivery system for cancerDrug delivery system for cancer

• DDrug targeting of tumorsrug targeting of tumors• MMaximize drug potency aximize drug potency

• MMinimize systemic toxicityinimize systemic toxicity.• Drug carrierDrug carrier Route of Route of

administationadministation●●LiposomeLiposome composed of one or more phospholipid bilayercomposed of one or more phospholipid bilayer Intravenous(iv)injection Intravenous(iv)injection

- e.g. liposome entrapped doxorubicine.g. liposome entrapped doxorubicin●●BeadBead

-e.g. drug-eluting microspheres/beads e.g. drug-eluting microspheres/beads Hepatic artery Hepatic artery(DEB) load with doxorubicin (DEB) load with doxorubicin

●●ProdrugProdrug-e.g prodrug of cisplatin using dextran e.g prodrug of cisplatin using dextran Intravenous(iv)injection Intravenous(iv)injection(galactose unit) (galactose unit)

Liver cancer treatmentLiver cancer treatment

Liver cancerLiver cancer

Localized unresectableLocalized unresectable Localized resectableLocalized resectable

liver transplantationliver transplantationSystemic chemotherapySystemic chemotherapy

Tumor embolizationTumor embolizationChemoembolizationChemoembolization

Hormone therapyHormone therapyRadiolabeled Radiolabeled

Segmental resection -Segmental resection -Trisegmental resectionTrisegmental resection

RecurrentRecurrent

Conventional drugsConventional drugs

• . DoxorubicinDoxorubicin

IV injectionIV injection

60-90 mg/m2- every 3 weeks60-90 mg/m2- every 3 weeks20-30 mg/m2/day - 3 days 20-30 mg/m2/day - 3 days

every 3 to 4 weeks.every 3 to 4 weeks.Dose depends upon whichDose depends upon which

regimen for cancer is beingregimen for cancer is being Poor risk patientPoor risk patient Reduce dosage Reduce dosage

IV infusionIV infusion

60-75 mg/m260-75 mg/m2- every 3 weeks- every 3 weeks

From

http://asia.mims.com, http://www.rxmed.com

Conventional drugsConventional drugs

5-FU5-FU

IV injectionIV injection

400 mg/m2 400 mg/m2 every 5 days every 5 days

repeated every repeated every 4 weeks (28-day)4 weeks (28-day)

OralOral(capecitabine)(capecitabine)

1250 mg/m2 1250 mg/m2 twice daily 2 weeks twice daily 2 weeks

1 week rest 1 week rest

From http://asia.mims.com, http://www.rxmed.com

Conventional drugs•

Cisplatin

IV infusion

50-100 mg/m2 every 3-4 week 15-20 mg/m2

daily for 5 days/week for 3-4 week.

From http://asia.mims.com, http://www.rxmed.com

Conventional drugs

Combretastatin

IV infusions

52 mg/m2 On day 1, 8, and 15.

courses repeat every 28 days

From: http://www.jco.org

Problem of conventional drugProblem of conventional drug

• Many side effectMany side effect - Drug effect on normal cell- Drug effect on normal cell

e.g. e.g. acute nausea, vomiting, mucositis, anorexia, diarrheaacute nausea, vomiting, mucositis, anorexia, diarrhea ,, • Less effectiveLess effective

- Drug cannot get into only liver but effect other organ- Drug cannot get into only liver but effect other organ• Too complicate in treatmentToo complicate in treatment

- For treat liver cancer use series of drug for more effectiveness- For treat liver cancer use series of drug for more effectiveness• Series of drugSeries of drug

- take time for inject the drugs- take time for inject the drugs- very painful because use large dose- very painful because use large dose

• ExpensiveExpensive• Drug resistanceDrug resistance

From:http://www.medicalillustrator.com

NanocellNanocell

• Nanocell is small particle between 10-1000nm.Nanocell is small particle between 10-1000nm.

- - less than 200 nm.less than 200 nm.

- Can pass through tumor blood vessels- Can pass through tumor blood vessels

- The outer shell- The outer shell anti-angiogenesis anti-angiogenesis

- The inner core - The inner core chemotherapy drugs. chemotherapy drugs.

- A "stealth" surface - A "stealth" surface

- avoid immune system- avoid immune system

From:http://www.medicalillustrator.com

From:http://www.medicalillustrator.com, http://www.3d4medical.com

Advantages of NanocellAdvantages of Nanocell

• Directly to the target site ( liver cancer)Directly to the target site ( liver cancer)• Less side effectLess side effect

- - Not effect on normal cellNot effect on normal cell

• Not complicate for treatmentNot complicate for treatment-- Inject only one time in one cycle of treatmentInject only one time in one cycle of treatment

• More effective More effective • Less invasive Less invasive

- - less pianfulless pianful-- less injection timeless injection time

• Economic price Economic price • Easy to injectEasy to inject

-- IV injectionIV injection

Compare Cost-benefitCompare Cost-benefitDrugDrug DoseDose Duration (1cycle)Duration (1cycle) Price ($)Price ($)

(6-8cycle)(6-8cycle)DoxorubicinDoxorubicin - IV injection- IV injection

- IV infusion- IV infusion

60-90 mg/m260-90 mg/m2

20-30 mg/m220-30 mg/m2

60-75 mg/m260-75 mg/m2

every 3 weeksevery 3 weeks

every day- 3 days every 3 to 4 weeksevery day- 3 days every 3 to 4 weeks

every 3 weeksevery 3 weeks

8,501.768,501.76

8,501.768,501.76

7,084.807,084.80

5-fu5-fu - IV injection- IV injection

- Oral- Oral

400 mg/m2 400 mg/m2

1250 mg/m21250 mg/m2

every day- 5 days repeated at 4 weeksevery day- 5 days repeated at 4 weeks

twice daily 2 weeks 1 week rest twice daily 2 weeks 1 week rest

11,808.0011,808.00

11,336.2211,336.22

CisplatinCisplatin - IV infusion- IV infusion 50-100 mg/m2 50-100 mg/m2

15-20 mg/m2 15-20 mg/m2

every 3 to 4 weekevery 3 to 4 week

daily 5 days/week for 3 to 4weeksdaily 5 days/week for 3 to 4weeks

227.78227.78

227.78227.78

CombretastatinCombretastatin - IV infusion- IV infusion 52or68mg/m2mg/m2 On day 1, 8, and 15 every 28 days 38,304.0438,304.04

NanocellNanocell - IV infusion- IV infusion 100100µl/kgBWµl/kgBW every 4 weeks every 4 weeks 4,546.894,546.89http://www.etonbio.com, http://www.hon.ch/News/HSN/527057.html,http://www.etonbio.com, http://www.hon.ch/News/HSN/527057.html, http://www.biotrend.com,http://www.biotrend.com, https://www.sigmaaldrich.com, http://www.rocheusa.comhttps://www.sigmaaldrich.com, http://www.rocheusa.com

Calculation profit

SaleSale CapitalCapital

(US$(US$)

RevenueRevenue Sale priceSale price

(US$(US$)

Profit Profit (1person ) (1person )

(US$(US$)RetailRetail 2,393.102,393.10 90%90% 4,546.894,546.89 2,153.792,153.79

WholesaleWholesale 2,393.102,393.10 50%50% 3,589.653,589.65 1,196.551,196.55

Ethical issuesEthical issues

• Liver cancer populationLiver cancer population- - high incidence in Asia.high incidence in Asia.

• Almost countries in Asia are Almost countries in Asia are - - developing countries developing countries

• Almost developing countries have Almost developing countries have - - a large number of poor people a large number of poor people

e.g. Thai GDP per capita income 2,221 US$ e.g. Thai GDP per capita income 2,221 US$

• ““Nanocell for developing countries”Nanocell for developing countries” -- economic priceeconomic price

Nanocell for developing countries

11,868 persons11,868 persons1995 – 19971995 – 1997

Sriamporn, et al(2002)Sriamporn, et al(2002)

SummarySummary

• So nanocell has been made for solving those problems of the conventional drugs

• For its price, there are two target groups

which are:

- the developing countries such as Thailand, Indonesia , it will be sold at whole sale

- the other countries at the retail.

AdditionAddition

Body surface area in m2 =Body surface area in m2 =

√ √ { height (cm) x weight (kg) }/3600{ height (cm) x weight (kg) }/3600

= 1.845 m2= 1.845 m2

Standard WHO Standard WHO

wieght wieght 7070 kgkg

HightHight 1.75 metre 1.75 metre

(from Norgan 1994)