SISTEM PENGHANTARAN OBAT TERTARGET · PDF fileSISTEM PENGHANTARAN OBAT TERTARGET Dhadhang...
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SISTEM PENGHANTARAN OBAT SISTEM PENGHANTARAN OBAT
TERTARGETTERTARGET
Dhadhang Wahyu Kurniawan@Dhadhang_WK
Laboratorium Farmasetika Unsoed
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LatarLatar BelakangBelakang
•• MasalahMasalah dengandengan sistemsistem penghantaranpenghantaran obatobatkonvensionalkonvensional::1.1. DistribusiDistribusi obatobat keke seluruhseluruh bagianbagian tubuhtubuh ––
tidaktidak hanyahanya didi tempattempat didi manamana obatobatdibutuhkandibutuhkan
2.2. KurangnyaKurangnya spesifitasspesifitas ikatanikatan obatobat terhadapterhadap2.2. KurangnyaKurangnya spesifitasspesifitas ikatanikatan obatobat terhadapterhadaptempattempat yang yang memerlukanmemerlukan –– organ targetorgan target
3.3. PerlunyaPerlunya memberikanmemberikan obatobat dalamdalam dosisdosisbesarbesar ((meskipunmeskipun yang yang diperlukandiperlukan sebetulnyasebetulnyakecilkecil))
4.4. ToksisitasToksisitas nonspesifiknonspesifik dandan efekefek sampingsampingyang lain yang lain selamaselama prosesproses terapiterapi (other (other adverse sideadverse side--effects)effects)
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SistemSistem PenghantaranPenghantaran ObatObat TertargetTertarget
�� MemungkinkanMemungkinkan obatobat untukuntukberakumulasiberakumulasi didi organ organ atauatau jaringanjaringan target target (yang (yang sakitsakit//membutuhkanmembutuhkan//tempattempat aksiaksi) ) secarasecara selektifselektif dandan kuantitatifkuantitatif terlepasterlepas didisecarasecara selektifselektif dandan kuantitatifkuantitatif terlepasterlepas didimanamana lokasinyalokasinya dandan bagaimanabagaimana caracarapemberianpemberian obatnyaobatnya
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SistemSistem PenghantaranPenghantaran ObatObat TertargetTertarget
•• KeuntunganKeuntungan::
1.1. DapatDapat menyederhanakanmenyederhanakan protokolprotokolpemakaianpemakaian obatobat
2.2. DosisDosis obatobat dapatdapat diturunkanditurunkan �� beayabeaya terapiterapi2.2. DosisDosis obatobat dapatdapat diturunkanditurunkan �� beayabeaya terapiterapijugajuga dapatdapat ditekanditekan
3.3. KonsentrasiKonsentrasi obatobat didi jaringanjaringan/organ//organ/reseptorreseptoryang yang memerlukanmemerlukan dapatdapat ditingkatkanditingkatkan secarasecarasignifikansignifikan tanpatanpa risikorisiko efekefek sampingsamping diditempattempat//jaringanjaringan yang lainyang lain
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SistemSistem PenghantaranPenghantaran ObatObat TertargetTertarget
•• KomponenKomponen “Magic Bullet”:“Magic Bullet”:
•• KomponenKomponen pertamapertama mengenalimengenali dandan berikatanberikatandengandengan organ/organ/jaringanjaringan//reseptorreseptor targettarget
•• KomponenKomponen keduakedua memberikanmemberikan efekefek terapiterapipadapada organ/organ/jaringanjaringan//reseptorreseptor targettargetpadapada organ/organ/jaringanjaringan//reseptorreseptor targettarget
•• DalamDalam prakteknyaprakteknya �� koordinasikoordinasi antaraantara::
•• ObatObat
•• TempatTempat targettarget
•• PembawaPembawa farmasetisfarmasetis
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PembawaPembawa FarmasetisFarmasetis
•• PolimerPolimer
•• MikrokapsulMikrokapsul
•• MikropartikelMikropartikel
•• SelSel
•• LipoproteinLipoprotein
•• LiposomLiposom
•• MiselMisel
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Liposom
�� Spherical vesicles with a phospholipid bilayerSpherical vesicles with a phospholipid bilayer
Hydrophilic
Hydrophobic
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Kegunaan Liposom
Chelation therapy for treatment of heavy metal
poisoning
Enzyme replacement
Diagnostic imaging of tumors
Study of membranes
Cosmetics
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Classes of Classes of LiposomesLiposomes
Conventional Long circulating
Immuno
Cationic
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Target Target SpesifikSpesifik
�� AntibodiAntibodi
�� LesitinLesitin dandan protein lainprotein lain
�� LipoproteinLipoprotein
HormonHormon�� HormonHormon
�� MolekulMolekul bermuatanbermuatan
�� PolisakaridaPolisakarida
�� LiganLigan berbobotberbobot molekulmolekul rendahrendah
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Modes of Liposome/Cell Interaction Modes of Liposome/Cell Interaction
Adsorption Endocytosis
Fusion Lipid transfer
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AplikasiAplikasi ObatObat secarasecara LangsungLangsung
•• PemberianPemberian obatobat langsunglangsung padapada tempattempat yang yang aktifaktif (organ (organ atauatau jaringanjaringan))
•• ContohContoh::
•• TerapiTerapi hormonhormon arthritisarthritis
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•• TerapiTerapi hormonhormon arthritisarthritis
•• TerapiTerapi padapada infarkinfark jantungjantung yang yang diinduksidiinduksioleholeh thrombusthrombus
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SistemSistem target target berbasisberbasis fisikafisika
•• PembawaPembawa akanakan berdisintegrasiberdisintegrasi padapada pH pH rendahrendahatauatau padapada temperaturtemperatur tinggitinggi
•• KondisiKondisi fisiologisfisiologis yang yang perluperlu diperhatikandiperhatikan::
•• pHpH
•• KondisiKondisi terionkanterionkan
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•• KondisiKondisi terionkanterionkan
•• EfekEfek makananmakanan
•• PengosonganPengosongan lambunglambung
•• Status Status enzimatikenzimatik, , proteolisisproteolisis
•• UsiaUsia
•• PerubahanPerubahan patofisiologispatofisiologis
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SistemSistem target target berbasisberbasis fisikafisika
•• TransporTranspor obatobat secarasecara magnetikmagnetik
KemampuanKemampuan obatobat untukuntuk terakumulasiterakumulasi didi tempattempatyang yang sakitsakit ditentukanditentukan oleholeh kecepatankecepatan aliranalirandarahdarah dandan intensitasintensitas medanmedan magnetikmagnetik yang yang
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darahdarah dandan intensitasintensitas medanmedan magnetikmagnetik yang yang digunakandigunakan
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Parameter Parameter penentupenentu efikasiefikasi dalamdalam
targetingtargeting
•• UkuranUkuran targettarget
•• AliranAliran darahdarah menujumenuju targettarget
•• JumlahJumlah tempattempat ikatanikatan untukuntuk obatobat dandan pembawapembawapadapada target target sasaransasaran
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padapada target target sasaransasaran
•• KemampuanKemampuan berikatanberikatan padapada tempattempat targettarget
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ContohContoh aplikasiaplikasi sistemsistem
penghantaranpenghantaran obatobat tertargettertargetpenghantaranpenghantaran obatobat tertargettertarget
padapada terapiterapi kankerkanker
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KankerKanker
•• PadaPada tahuntahun 2000, 1,4 2000, 1,4 jutajuta kasuskasus
•• 560.000 560.000 kematiankematian �� lebihlebih daridari 1.500 1.500 orangorang per per tahuntahun
•• Di USA Di USA �� 25% 25% angkaangka kematiankematian karenakarena kankerkanker•• Di USA Di USA �� 25% 25% angkaangka kematiankematian karenakarena kankerkanker
•• BeayaBeaya terapiterapi kankerkanker::
•• $37 $37 milyarmilyar �� beayabeaya terapiterapi
•• $11 $11 milyarmilyar �� beayabeaya penurunanpenurunan produktivitasproduktivitas
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Di USADi USA
•• Survival rate Survival rate untukuntuk 5 5 tahuntahun �� 64%64%
•• RisikoRisiko terjangkitterjangkit kankerkanker::
•• < ½ (< ½ (lakilaki--lakilaki))
•• > 1/3 (> 1/3 (wanitawanita))•• > 1/3 (> 1/3 (wanitawanita))
•• BeayaBeaya total total untukuntuk kankerkanker padapada tahuntahun 2004 2004 ��
$189,8 $189,8 milyarmilyar
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TipeTipe TerapiTerapi KankerKanker
•• PembedahanPembedahan �� membuangmembuang massamassa tumor yang tumor yang diketahuidiketahui
•• RadiasiRadiasi �� membunuhmembunuh dengandengan cepatcepat selsel kankerkanker yang yang aktifaktif membelahmembelah termasuktermasuk selsel tumor yang tumor yang adaada padapadaorgan/organ/jaringanjaringan
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•• KemoterapiKemoterapi �� membunuhmembunuh dengandengan cepatcepat selsel kankerkankeryang yang aktifaktif membelahmembelah
•• TerapiTerapi hormonhormon �� menghambatmenghambat pertumbuhanpertumbuhan dandansurvival survival selsel--selsel kankerkanker yang yang tergantungtergantung hormonhormon
•• SistemSistem penghantaranpenghantaran tertargettertarget �� secarasecara spesifikspesifikmenghambatmenghambat prosesproses yang yang diperlukandiperlukan pertumbuhanpertumbuhan selseltumortumor
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ContohContoh terapiterapi tertargettertarget
•• PengembanganPengembangan Targeted Targeted NanoNano Therapeutics (TNT) Therapeutics (TNT) oleholehTritomTritom BioSystemBioSystem bersamabersama Army Research Lab.Army Research Lab.
•• PrinsipPrinsip kerjakerja TNT TNT �� 3 3 tahapantahapan::
1.1. PasienPasien menerimamenerima infusinfus mengandungmengandung triliunantriliunan bioprobebioprobe
(bola (bola magnetikmagnetik berukuranberukuran nanonano yang yang berikatanberikatan dengandengan(bola (bola magnetikmagnetik berukuranberukuran nanonano yang yang berikatanberikatan dengandengan
antibodiantibodi))
2.2. BioprobeBioprobe akanakan mencarimencari dandan menangkapmenangkap selsel kankerkanker padapada
pembuluhpembuluh darahdarah
3.3. DokterDokter akanakan menghidupkanmenghidupkan medanmedan magnetikmagnetik didi tempattempat didi
manamana terdapatterdapat kankerkanker�� bioprobebioprobe akanakan berkumpulberkumpul padapada
tempattempat tersebuttersebut�� pemanasanpemanasan akanakan membunuhmembunuh selsel kankerkanker
dalamdalam beberapabeberapa menitmenit
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BagaimanaBagaimana konsepkonsep iniini bekerjabekerja??
•• SelSel tumor tumor dandan kankerkanker akanakan matimati padapada suhusuhu
4343°°C. C. SelSel normal normal dapatdapat bertahanbertahan sampaisampai --4949°°C.C.
•• DenganDengan material material ferriferri-- atauatau ferroferro-- magnetite magnetite ��
pemanasanpemanasan padapada tempattempat didi manamana medanmedan
magnetikmagnetik diberikandiberikan �� selsel kankerkanker terbunuhterbunuh..magnetikmagnetik diberikandiberikan �� selsel kankerkanker terbunuhterbunuh..
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Colon Targeted Drug
Delivery
System
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Anatomy of colon
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Applikasi
In local colonic pathologies
Systemic delivery of protein and peptide
Potential site for the treatment of Potential site for the treatment of diseases liike asthma,arthritis & angina
For the drugs that are absorbed through colon such as steroids
For the treatment of disorders like IBS (Inflammatory Bowel Disease, colitis, crohn’s disease where it is necessary to attain high concentration of drugs in
colon
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Limitation and Challenges
Dissolution in luminal fluid.
Stability of drugs.
Binding of drugs to dietary residues, intestinal secretions, mucus or fecal
matter.
Metabolic degradation by colonic microflora.
Wide range of pH values
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Lower surface area and relative “tightness” of the tight junctions in the colon restrict drug transport.
Longer residence time
Requires protection against variety of the gastric enzymes.
Cytochrome P450 3A class of drug metabolizing enzymes have lower activity in colon
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Target sites Disease conditions
Drugs used
Topical/local action
Inflammatory bowel disease,
Hydrocortisone, Budenoside,
Introduction to colonic
drug delivery system
action bowel disease, Irritable bowel
syndrome &crohn’disease
Budenoside, Prednisolone, Sulphasalazine, Olsalazine, InfliximabMesalazine, Balsalazide, 6-Mercaptopurine, Azathiorprine, Cyclosporine,etc
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Amoebiasis Metronidazole, Ornidazole, Tinidazole, Mebandazole, etc
Chronic pancreatitis,
Digestive enzyme supplements pancreatitis,
Pacreatactomyand Cystic fibrosis
supplements
Colorectal cancer 5-Fluoro uracil
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Systemic action
To prevent gastric irritation
NSAIDS
To prevent first pass metabolism of orally ingested drugs
Steroids
ingested drugs
Oral delivery of peptides
Insulin
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Factor affecting
Colonic
drug Delivery
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Pharmaceutical Pharmaceutical
approaches for CDDSapproaches for CDDS
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Approaches
1. Prodrug2. Osmotically controlled drug
delivery3. Redox-sensitive polymers
4. pH dependent system4. pH dependent system5. Time dependent system6. Microflora activated system7. Pressure controlled system8. Bioadhesive systems9. Micro particulate system
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