SEL MEMBRAN, SEL MEMBRAN, EPITELIAL, DAN EPITELIAL, DAN ABSORPSI OBATABSORPSI OBAT

NI LUH DEWI ARYANINI LUH DEWI ARYANI

PENDAHULUANPENDAHULUAN

ORGAN

JARINGAN

SEL

• SITOPLASMA:cairan aqueous, tempat terjadinya proses biokimia

• NUKLEUS:tempat DNA (informasi genetik)

• MEMBRAN SEL: mengelilingi dan mencegah sitoplasma agar tidak bercampur dengan sekelilingnya

SEMIPERMEABEL

SEL EPITELIAL•Mengelilingi jaringan & organ”membran luar organ atau jaringan”•Bound organ•Tempat proses transpor, sekresi dan barrier organ tertentu

OBAT

TARGET ORGAN

TEMPAT APLIKASI

SIRKULASI SISTEMIK / SITOPLASMA SEL TERTENTU

MELINTASI JARINGAN & EPITELIAL (ABSORPSI): INTERSELULAR

INTRASELULAR

STRUKTUR & FUNGSIMEMBRAN SEL & JARINGAN

EPITEL

STRUKTUR & FUNGSISTRUKTUR & FUNGSIMEMBRAN SELMEMBRAN SEL

ANATOMIANATOMI KOMPOSISIKOMPOSISI FUNGSIFUNGSI TEBALTEBAL Selaput Selaput Membran Membran

oKhondroitin Khondroitin HH22SOSO44

oAsam Asam Hialuronat Hialuronat oElastin Elastin oAsam SialatAsam Sialat

oKomponen Utama Komponen Utama Jaringan Jaringan Konvektif Konvektif oKomponen Komponen AdsorpsiAdsorpsi

??

Membran Membran Sel Sel

oProtein Protein oTrigliserida Trigliserida Kholesterol Kholesterol Lesitin Lesitin (fosfolipida ) (fosfolipida ) oProteinProtein

oLapisan Lapisan hidrofilikhidrofilikoLapisan Lapisan lipofilik lipofilik (barrier (barrier bimolecular)bimolecular)

oLapisan Lapisan Hidrofilik Hidrofilik

o25 A 25 A o35 A35 A

o25 A 25 A

MEMBRAN BIOLOGIK :MEMBRAN BIOLOGIK :

PERMUKAAN MEMBRAN SEL YANG PERMUKAAN MEMBRAN SEL YANG BERPERAN SEBAGAI “ BARRIER BERPERAN SEBAGAI “ BARRIER ” ANTARA UNIT MORFOLOGIK ” ANTARA UNIT MORFOLOGIK DENGAN UNIT FUNGSIONAL DI DENGAN UNIT FUNGSIONAL DI DALAM SEL DALAM SEL

MODEL STRUKTUR MEMBRANMODEL STRUKTUR MEMBRAN          

Langmuir TroughsLangmuir Troughs  Model Bilayer Model Bilayer                 Model Davson-Danielli Model Davson-Danielli Model Singer-Nicolson Model Singer-Nicolson         Glikoprotein disekresi oleh sel = Glikoprotein disekresi oleh sel = “dinding sel”“dinding sel”

Model Fluid Mosaic Model Fluid Mosaic         Extra-cellular MatrixExtra-cellular MatrixPada sel hewanPada sel hewan

Langmuir TroughsLangmuir Troughs

Gorter and Grendel1925

Model BilayerModel Bilayer

Model Davson-DanielliModel Davson-Danielli

Model Singer-NicolsonModel Singer-Nicolson

Model Fluid Mosaic Model Fluid Mosaic 

Extra-cellular MatrixExtra-cellular Matrix

Model Fluid MosaicModel Fluid Mosaic

1.Lipids 1.Lipids      t.u phospholipids  &  cholesterolt.u phospholipids  &  cholesterol

lipid fluidity - viscous vs. fluidlipid fluidity - viscous vs. fluid

2.Proteins   2.Proteins               a)a)   Integral (intrinsic) proteinsIntegral (intrinsic) proteins  

- denatured upon - denatured upon releaserelease b)b)   Peripheral (extrinsic)   Peripheral (extrinsic)     

-  easily extractable-  easily extractable

Struktur FosfolipidStruktur Fosfolipid

SIFAT AMPIFILIKPOLAR HEAD:-CHOLINE (PC)-SERINE (PS)-ETHANOLAMINE (PE)-INOSITOL (PI)

NONPOLAR HEAD:12-24 ATOM KARBON

KOLESTEROL: KOLESTEROL: MENSTABILKAN MEMBRANMENSTABILKAN MEMBRAN

SIFAT DINAMIKA MEMBRAN:SIFAT DINAMIKA MEMBRAN:lipid fluidity - viscous vs. fluidlipid fluidity - viscous vs. fluid

FAKTOR:TEMPERATUR TRANSISI

RANTAI HIDROKARBON ASAM LEMAK DI FOSFOLIPID-TIDAK JENUH (LOW)- JENUH (HIGH)

MISEL & LIPOSOM: MISEL & LIPOSOM: Bentuk Lain dari konfigurasi LipidBentuk Lain dari konfigurasi Lipid

STRUKTUR FOSFOLIPID STRUKTUR FOSFOLIPID MISEL DAN LIPOSOM MISEL DAN LIPOSOM MISEL MISEL TERBENTUK BILA RASIO JUMLAH LIPID RELATIF LEBIH SEDIKIT TERBENTUK BILA RASIO JUMLAH LIPID RELATIF LEBIH SEDIKIT

DIBANDING AIRDIBANDING AIR

Asymmetry of Lipid BilayerAsymmetry of Lipid Bilayer Outside:Outside:

more more phosphatidylcholiphosphatidylcholine (red)ne (red)

Inside:Inside: more more

phosphatidylserinphosphatidylserine (green)e (green)

Glycolipids:Glycolipids: only on outside only on outside

face (blue)face (blue)

INTEGRAL PROTEININTEGRAL PROTEINBERTANGGUNGJAWAB TERHADAP BERTANGGUNGJAWAB TERHADAP PERPINDAHAN MOLEKUL DARI DAN KELUAR SELPERPINDAHAN MOLEKUL DARI DAN KELUAR SEL

PERIPHERAL PROTEINPERIPHERAL PROTEIN

CELL SURFACE RECEPTOR: HISTAMIN RESEPTOR, CELL SURFACE RECEPTOR: HISTAMIN RESEPTOR, PROSTAGLANDIN,DSBPROSTAGLANDIN,DSB

GLYCOPROTEINGLYCOPROTEININTEGRAL PROTEIN CARRYING INTEGRAL PROTEIN CARRYING POLYSACCHARIDES POLYSACCHARIDES RESPONSIBLE FOR IMUNOLOGICAL RESPONSIBLE FOR IMUNOLOGICAL BEHAVIOURBEHAVIOUR

GLYCOCALYXGLYCOCALYXGLYCOLIPID ANCHORGLYCOLIPID ANCHOR FIBRONECTIN FIBRONECTIN (PERIPHERAL PROTEIN)(PERIPHERAL PROTEIN)CONTAIN EXTRACELULUAR PROTEIN CONTAIN EXTRACELULUAR PROTEIN SUCH AS COLLAGEN, POLYSACCHARIDASUCH AS COLLAGEN, POLYSACCHARIDA INTERSELUAR INTERSELUAR BINDING & TISSUE FORMATIONBINDING & TISSUE FORMATION

MEMBRAN PROTEINMEMBRAN PROTEIN

Association of Proteins with the Cell Association of Proteins with the Cell MembraneMembrane

PROTEIN may be linked to the membrane by a PROTEIN may be linked to the membrane by a glycolipidglycolipid or or phospholipid anchorphospholipid anchor. .

EPITHELIAEPITHELIA epitheliumepithelium is a is a tissuetissue composed of a layer of composed of a layer of cellscells. Epithelium can be found lining internal . Epithelium can be found lining internal (e.g. (e.g. endotheliumendothelium, which lines the inside of , which lines the inside of blood vessels) or external (e.g. blood vessels) or external (e.g. skinskin, , corneacornea) ) free surfaces of the body.free surfaces of the body.

The outermost layer of our The outermost layer of our skinskin is composed of is composed of dead dead squamoussquamous epithelial cells, as are the mucous epithelial cells, as are the mucous membranes lining the inside of mouths and body membranes lining the inside of mouths and body cavities. Other epithelial cells line the insides cavities. Other epithelial cells line the insides of the of the lungslungs, the , the gastrointestinal tractgastrointestinal tract, the , the reproductive and urinary tracts, and make up the reproductive and urinary tracts, and make up the exocrine and endocrine glands.exocrine and endocrine glands.

Functions of epithelial cells include secretion, Functions of epithelial cells include secretion, absorption and protection. Epithelial cells sit absorption and protection. Epithelial cells sit on a on a basal laminabasal lamina (formerly called a basement (formerly called a basement membrane).membrane).

ClassificationClassificationEpithelial cells are classified by the following Epithelial cells are classified by the following three factors:three factors:

Shape Shape SquamousSquamous CuboidalCuboidal ColumnarColumnar

Stratification (number of layers) Stratification (number of layers) SimpleSimple: : StratifiedStratified: : PseudostratifiedPseudostratified: : TransitionalTransitional: :

SpecializationSpecialization KeratinizationKeratinization / / CornificationCornification: : CiliatedCiliated:: Brush borderBrush border / / MicrovilliMicrovilli: : StereociliaStereocilia: :

ExamplesExamples Simple squamousSimple squamous: :

Found in Found in blood vesselsblood vessels & lymph channels (called & lymph channels (called endothelium) and body cavities (called mesothelium) endothelium) and body cavities (called mesothelium)

Keratinized stratified squamousKeratinized stratified squamous:: Found in Found in human skinhuman skin (specifically, the dead superficial (specifically, the dead superficial layer) layer)

Stratified squamousStratified squamous:: Found in human Found in human oesophagusoesophagus

Simple cuboidalSimple cuboidal: : Found in Found in thyroidthyroid follicles follicles

Stratified cuboidalStratified cuboidal: : Exclusively found in Exclusively found in sweat gland ductssweat gland ducts

Ciliated simple columnarCiliated simple columnar: : Found in Found in intestineintestine and kidney (specifically, distal and kidney (specifically, distal convoluted tubule) convoluted tubule)

Stratified columnarStratified columnar: : Ducts of submandibular glandsDucts of submandibular glands

TransitionalTransitional:: Specialized to distend (stretch) as the Specialized to distend (stretch) as the urinary bladder urinary bladder fills fills

CELL JUNCTIONSCELL JUNCTIONS EPITHELIAL CELL ARE BONDED BY CELL EPITHELIAL CELL ARE BONDED BY CELL JUNCTIONS (PREVENT DIFFUSION OF SOLUT JUNCTIONS (PREVENT DIFFUSION OF SOLUT AROUND THE CELL):AROUND THE CELL): TIGHT JUNCTIONSTIGHT JUNCTIONS

• MAINTAINING THE SELECTIVE BARRIER FUNCTION OF MAINTAINING THE SELECTIVE BARRIER FUNCTION OF CELL SHEETCELL SHEET

• IMPERMEARBLE TO COLLOIDAL PARTICLE, SMALL IMPERMEARBLE TO COLLOIDAL PARTICLE, SMALL PARTICLE, AND ION, AND POSSIBLY EVEN TO WATERPARTICLE, AND ION, AND POSSIBLY EVEN TO WATER

GAP JUNCTIONSGAP JUNCTIONS• MOLECULES UP TO 1200 DALTONS CAN PASS FREELY MOLECULES UP TO 1200 DALTONS CAN PASS FREELY THROUGH GAPS, BUT MACROMOLECULES CANNOTTHROUGH GAPS, BUT MACROMOLECULES CANNOT

DESMOSOMESDESMOSOMES• SMALL STRUCTURE WHICH BOND ADJACENT CELL SMALL STRUCTURE WHICH BOND ADJACENT CELL TOGETHER TOGETHER spot, bel, and hemidesmosomes spot, bel, and hemidesmosomes

MEKANISME TRANSPORTMEKANISME TRANSPORTMEKANISMEMEKANISME KARAKTERISTIKKARAKTERISTIK CONTOHCONTOH

Difusi Difusi pasifpasif

pKa, P, pH, pKa, P, pH, perbedaan perbedaan konsentrasi, , konsentrasi, , luas area dan luas area dan ketebalan ketebalan membran, Dmembran, D

Asam-basa Asam-basa lemah, lemah, nonelektrnonelektrolitolit

Absorpsi Absorpsi konvektif konvektif (pori)(pori)

d. porid. pori~ 7~ 7ǺǺ, , perpindahan perpindahan pelarut, pelarut, perbedaan perbedaan tekanan tekanan hidrostatik, hidrostatik, luas permukaan, luas permukaan, tebal membran, tebal membran, jumlah pori, jumlah pori, viskositas, viskositas, muatan listrikmuatan listrik

ElektroliElektrolit BM < t BM < 150-400, 150-400, ion ion muatan muatan berlawanaberlawanan dgn n dgn sal. porisal. pori

MEKANISME ABSORPSIMEKANISME ABSORPSIMEKANISMEMEKANISME KARAKTERISTIKKARAKTERISTIK CONTOHCONTOH

Transport Transport AktifAktif

Pembawa, Pembawa, melawan melawan perbedaan kons, perbedaan kons, kejenuhan, kejenuhan, spesifik, spesifik, competitive competitive inh., poisoning inh., poisoning of carrierof carrier

Na, K, I-, Na, K, I-, Fe2+, Fe2+, Ca2+,monosaCa2+,monosakarida, karida, asam amino, asam amino, testosterontestosteron, estradiol, estradiol

Difusi Difusi TerfasilitaTerfasilitasisi

Pembawa, Pembawa, kejenuhan, kejenuhan, spesifik, spesifik, competitive competitive inh., poisoning inh., poisoning of carrier, dgn of carrier, dgn perbedaan kons.perbedaan kons.

Vitamin Vitamin B12B12

MEKANISME TRANSPORTMEKANISME TRANSPORTMEKANISMEMEKANISME KARAKTERISTIKKARAKTERISTIK CONTOHCONTOH

Transport Transport visikular : visikular : PinositosisPinositosis

Pencaplokan Pencaplokan molekul obatmolekul obat

Fat, Vit Fat, Vit A,D, E. KA,D, E. K

Pasangan IonPasangan Ion Komplek bag. Komplek bag. Anion organik Anion organik dgn kation dgn kation membranmembran

Amm. Amm. Kuartener, Kuartener, asam asam sulfonatsulfonat

MUCUSMUCUSCELL EPITHELIALCELL EPITHELIAL DIFFERENT TYPE & FUNCTION DIFFERENT TYPE & FUNCTION

MUCOSAL CELL SECRETES MUCUS MUCUSAL EPHITHELIUM OR SIMPLE MUCOSA

FUNCTIONS OF MUCUS:- Restricted the penetration of large molecules - Prevent the tissue from dehydrating- Keep surface clean by its continuous removal- Lubricates the passage material

Component ?

MUCUS: 95%WATER INTIMATES CONTACT WITH HIDROPHILIC SURFACE.Small particle < 600 um buried in the surface & held securely since the stickness of the mucus mucus secreted particle move awaySmall particle pass/ diffuse through mucus easly, large molecules more slowy

MUCOADHESIVE DRUG DELIVERY SYSTEMS