This document discusses membrane transporters and their role in drug response. It begins with an overview of the basic transport mechanisms, including passive diffusion, facilitated diffusion, and active transport. It then describes the two major families of membrane transporters - ATP-binding cassette (ABC) transporters and solute carrier (SLC) transporters. The document reviews the structure and mechanisms of ABC and SLC transporters and provides examples of specific transporters involved in the absorption, distribution, and excretion of drugs.

1. MembraneTransporters
and Drug Response
Dr.Soujania Singh
1st year PG ,Pharmacology
Sree Balaji Medical College &
Research Institute

2. OVERVIEW
• Introduction
• Basic Transport mechanism
• Membrane Transporters- ABC & SLC family
• Regulation of Transporter expression
• Transporters involved in pharmacokinetics
# Intestinal Transporters
# Hepatic transporters
# Renal transporters
• Transporters involved in pharmacodynamics
• Membrane transporters & drug resistance
• Novel approach

3. INTRODUCTION
• The movement /translocation of drug from one side of biological barrier
to the other is called the transport mechanism
• Membrane transport proteins are present in all organisms.
• Influx of essential nutrients and ions
• Efflux of cellular waste, environmental toxins, drugs, and other
xenobiotics

4. BASICTRANSPORT MECHANISM
PARA-CELLULAR DIFFUSION
PASSIVE
TRANSPORT
FACILITATED
DIFFUSION
PRIMARY SECONDARY
ACTIVE
SLC
ANTIPORT
ABC
SYMPORT
SLC Co-
Transporters
SLC Exchange
Transporters

5. Passive Diffusion(Down Hill)
• Simple diffusion of a solute across the plasma
membrane – 3 process
i. Partition from the aqueous to the lipid phase,
ii. Diffusion across the lipid bilayer
iii. Repartition into the aqueous phase on the opposite side.
• Passive diffusion of any solute (including
drugs) occurs down an electrochemical
potential gradient of the solute.
• Eg: Phenytoin Sodium ,Sodium Salicylate,
Morphine HCL, Atropine Sulphate
Electrochemical potential gradient
of the substrate
High Low

6. Facilitated Diffusion
• Diffusion of ions and organic compounds across the
plasma membrane ,facilitated by a membrane
transporter
• Transporter-mediated membrane transport that
does not require energy input (SLC Transporters)
• Diffusion of compounds across the plasma
membrane occurs down their electrochemical
potential gradients.
• Steady state will be achieved when the
electrochemical potentials of a compound on both
sides of the membrane become equal.
• Eg:AA in Brain, Anti-Cancer Drug, Anti-Viral
Drug,Vitamins
Electrochemical potential gradient
of the substrate
High Low

7. Filtration/ParacellularTransport
• Passage of solutes and fluid through intercellular gaps
• Eg: endothelium of capillaries and Postcapillary venules
• Capillaries of the CNS and a variety of epithelial tissue
have tight junctions that limit paracellular movement of
drugs

8. ActiveTransport(Up Hill)
• Energy -dependent, carrier-mediated transport taking place
against the electrochemical gradients
• Active transport plays an important role in the uptake and
efflux of drugs and other solutes.
• Active Transport -
Primary Active Transport
Secondary Active Transport
Tertiary Active Transport

9. Primary ActiveTransport
• Membrane transport that directly
couples with ATP hydrolysis is
called primary active transport.
• ABC transporters are examples of
primary active transporters
• ABC transporters mediate the
unidirectional efflux of solutes
across biological membranes
• Another example Na+,K+-ATPase
ATP
ADP

10. Secondary ActiveTransport
• The transport across a biological membrane of a solute S1 against its
concentration gradient is energetically driven by the transport of another
solute S2 in accordance with its electrochemical gradient.
ANTIPORT/EXCHANGE
TRANSPORTERS
The transporter moves S2
and S1 in opposite
directions
Eg:Na+/Ca++ exchanger
SYMPORTERS /
CO-TRANSPORTERS
The transporter moves S2
and S1 in the same
direction
Eg: Na+-glucose
transporter SGLT1

11. ANTIPORTSYMPORT

12. Tertiary ActiveTransport
 Tertiary active transport also requires an
ATPase-dependent sodium gradient
 Sodium influx facilitates the diffusion and
intracellular accumulation of an anion such as
bicarbonate via a secondary active transporter.
 Tertiary active transport, the solute carrier
exports the intracellular anion in exchange or
the uptake of an extracellular organic anion
HCO3-uphill
NA+-downhill
HCO3-Downhill

13. BasicTransport Mechanism

14. Types Of MembraneTransporters
• ABC -ATP Binding Cassette superfamily of transporters
• SLC-Solute Linked Carrier group of transporters.

15. ABC-ATP Binding Cassette
• The ABC superfamily includes 49 genes, each containing one or
two conserved ABC regions.
• It is grouped into 7 sub-classes(ABCA to ABCG)
• The core catalytic ABC regions of these proteins bind
and hydrolyze ATP, using the energy for uphill transport of their
substrates
• Most ABC transporters move compounds from the cytoplasm to the
cell exterior or into an intracellular compartment (endoplasmic
reticulum, mitochondria, peroxisomes).

16. ABCTransporter-Structure
• ABC Transporters consists of two distinct domains, The
Trans Membrane Domain(TMD) and the Nucleotide
Binding Domain(NBD)
• The TMD also known as Membrane Spanning Domain
(MSD)or Integral Membrane(IM) domain, consists of
alpha helices embedded in the membrane bilayer
• It recognizes variety of substrates and undergoes
conformational changes to transport the substrate
across the membrane
• Eg:P-gp glycoprotein encoded by ABCB1 also termed
MDR1 and CFTR(Cystic Fibrosis Transmembrane
Regulator)

17. ABCTransporter-Structure contd..
• NBDs on the cytoplasmic side participate in binding and
hydrolysis of ATP.
• Crystal structures of ABC transporters show two NBDs, which are
in contact with each other.
• In most exporters, the N-terminal transmembrane domain and
the C-terminal ABC domains are fused as a single polypeptide
chain, arranged asTMD-NBD-TMD-NBD.
• Importers have an inverted organization, that is, NBD-TMD-
NBD-TMD, where the ABC domain is N-terminal whereas the
TMD is C-terminalTransporters

18. #TMD-Trans Membrane Domain
#NBD-Nucleotide Binding Domain
ABCTransporters-Structure

19. ABC-Structure contd……
• Some ABC superfamily transporters contain only a single ABC motif, they
form homodimers (BCRP/ABCG2) or heterodimers (ABCG5 and ABCG8) that
exhibit a transport function.
P-gp
ABCB1
ABCG5,ABCG8

20. The resting state of
importers is inward-
facing
On association to a
substrate-binding protein
promotes ATP-dependent
NBD closure, causing the
TMDs to expose an extra-
cytosolic substrate-binding
cavity
. The substrate-
binding protein
releases its substrate
into the transporter’s
binding cavity
Hydrolysis of both
ATP molecules
NBD dimer opens
and substrate is
released into the
cytoplasm
Importer-Mechanism(Alternating Access Model)

21. 1.The transport cycle is
started by binding of a
substrate to a high-
affinity pocket formed
by the TMDs
3.Major conformational
change in the TMDs, with
TMDs rotating and
opening toward the
outside, initiating
substrate translocation
2.A conformational
change is transmitted to
the NBDs , facilitating
ATP binding and closed
NBD-dimer formation.
4.ATP hydrolysis initiates
dissolution of the closed NBD
dimer, resulting in further
conformational changes in the
TMDs
5.Phosphate and ADP
release restores the
transporter to open
NBD-dimer
conformation
Exporter-Mechanism(ATP-Switch Model)

22. ABC TRANSPORTERS ABSORPTION,DISTRIBUTION AND EXCRETION PROCESS
MDR1 (ABCB1)/
P-gp
Liver, kidney,
intestine,
BBB, BTB, BPB
Endogenous
Phospholipids
Drugs
fexofenadine, loperamide, digoxin
(neutral &cationic compounds)
MRP1 (ABCC1) Ubiquitous Vincristine, methotrexate
MRP2 (ABCC2) Liver, kidney,
intestine, BPB
statins, Ang II receptor
antagonists
MRP3 (ABCC3) Liver, kidney, intestine etoposide, morphine
MRP4 (ABCC4) Ubiquitous, including
BBB and
BCSFB
methotrexate; estradiol glucuronide
ABC TRANSPORTERS
#BBB-Blood Brain Barrier #BTB-BloodTesticular Barrier,
#BPB-Blood Placental Barrier #BCSFB-Blood CSF Barrier

23. ABCTransporters
ABC TRANSPORTERS ABSORPTION,DISTRIBUTION AND EXCRETION PROCESS
MRP5 (ABCC5) Ubiquitous cyclic AMP/GMP; adefovir
MRP6 (ABCC6) Liver, kidney Doxorubicin, etoposide
BCRP(MXR) (ABCG2) Liver, intestine, BBB topotecan, imatinib,Statins
(neutral &anionic compounds)
MDR3 (ABCB4) Liver Endogenous-Phospholipids
Drugs-Paclitaxel,vinblastine
digoxin
BSEP (ABCB11)
Bile salt export pump
Liver Endogenous
Bile salts,taurocholate
Drugs-pravastin,vinblastine
ABCG5, ABCG8 Liver, intestine Plant sterols

24. ABCTransporters Mutation- Human Genetic Disorders
Gene Family Examples of human diseases
ABCA ABCA Tangier’s Disease (ABCA1)
ABCB ABC B X-linked sideroblastic anemia with ataxia (ABCB7)
ABCC ABC C Dubin-Johnson syndrome (MRP2/ABCC2)
ABCD ABC D Adrenoleukodystrophy (ABCD1)
ABCE ABC E -
ABCF ABC F -
ABCG ABC G Sitosterolemia (ABCG5 and ABCG8)

25. SLC-Transporters
• 52 SLC Families with 395 genes have been identified in the human genome
• Serve as channels, facilitators(Glucose Transporters GLUT) ,secondary active
transporter(OATs,OATPs,SGLT)
• Many serve as drug targets or in drug absorption and disposition
• Eg: Seratonin(5-HT)(SLC 6A4),Dopamine transporters(SLC6A3)
• SLC transporters - drug absorption, elimination,tissue distribution and
importantly as mediators of drug-drug interactions.

26. SLC-Mechanism
• SLC transporters may use an alternating access, and the gated pore
mechanism
• Transporter undergoes a reversible conformational change between the
two sides of the membrane during the translocation process

27. SLC-Mechanism contd…..
Substrate
accesses the
substrate
binding site
on one side of
the
membrane
Substrate binding induces structural
changes in the carrier protein,
reorienting the opening of the
binding site to the opposite side
The substrate
dissociates from
the transport site
Allowing another
substrate to be
bound and
transported

28. SLC-Expression in body
SLC -Families Expression
SLC1, SLC3, SLC6, SLC7, SLC25, and SLC36 IntestineAnd Kidney
SLC2, SLC5, and SLC50 GlucoseAnd Other Sugars
SLC11, SLC30, SLC39, and SLC40 Transport Water-solubleVitamins
SLC6 Neurotransmitters AcrossThe Plasma
Membrane
SLC18 Transport Neurotransmitters Into Storage
Vesicles

29. SLC-Interaction
SLC Family Interactions
Solute carrier organic anion family,SLCO Statins And Antidiabetic Drugs
SLC22 AnionicAnd Cationic Drugs, Antibiotics
And Antiviral Agents
SLC30A8 Polymorphism Type 1 Diabetes Mellitus
SLC22A4 and SLC22A5 Polymorphism Inflammatory Bowel Disease.

30. SLC UptakeTransporters
• Organic Anion Transporting Polypeptide(OATP)
• Organic Anion Transporter(OAT)
• Organic Cation Transporter(OCT)
• Bile Acid Transporter Family
• Peptide transporter family(PEPT)
• Glucose Transporters(GLUT,SGLT)

31. VectorialTransport
• Asymmetrical transport across a monolayer of polarized cells is
called vectorial transport.

32. VectorialTransport
• The ABC transporters mediate only unidirectional efflux, whereas SLC
transporters mediate either drug uptake or drug efflux.
• For lipophilic compounds that have sufficient membrane permeability,
ABC transporters alone are able to achieve vectorial transport without
the help of influx transporters
• For hydrophilic organic anions and cations, coordinated uptake and efflux
transporters in the polarized plasma membranes are necessary to
achieve the vectorial movement of solutes across an epithelium.

33. Transporters-Vectorial transport

34. Regulation ofTransporter Expression
• Regulated transcriptionally in response to drug treatment and
pathophysiological conditions, resulting in induction or downregulation
of transporter mRNAs
• Type II nuclear receptors, which form heterodimers with the 9-cis-
retinoic acid receptor (RXR), can regulate transcription of genes for drug-
metabolizing enzymes and transporters
• Pregnane X Receptor PXR
• Constitutive Androstane X Receptor CAR
• Farnesoid X Receptor FXR
• Peroxisome Proliferator-activated Receptor α PPARα
• Retinoic Acid Receptor RAR

35. PXR-Target
Gene
Function
Drugs,xenobiotics
(blood and bile)
Excrete Drugs and Xenobiotics
(Urine,Bile)
Drugs,Xenobiotics
PXR
Liver
Intestine
Kidney
Increaser PXR target
Gene Expression
PXR Activation Regulates Drug Inducible Gene Expression Thus
Eliminating Toxic Substances From Blood And Bile

36. Regulation ofTransporter Expression contd….
• PXR( SXR)-is activated by clotrimazole, phenobarbital, rifampicin,
ritonavir, carbamazepine, phenytoin, sulfadimidine, paclitaxel
• PXR mediates co-induction of CYP3A4 and Pgp, supporting their synergy
in efficient detoxification.
• DNA methylation –Epigenetic control of gene expression- OAT3, URAT1,
OCT2, OATP1B2, NTCP, and PEPT2 in the SLC families and MDR1, BCRP,
BSEP, and ABCG5/ABCG8 (ABC)

37. Physiological Role Of MembraneTransporters
• Regulating the Distribution and Bio-Availability of Drugs
• Removal of toxic metabolite and xenobiotics from cells in to urine, bile
and the intestinal lumen.
• The transport of compounds out of the brain across the blood brain
barrier
• Protection of hematopoietic stem cells from toxins

38. Pharmacological Role of Membrane
Transporters

39. Transporters-Pharmacokinetics
•Intestinal Transporters
•Hepatic Transporters
•Renal Transporters

40. IntestinalTransporters
PEPT1
• β lactam antibiotics
• ACE 1 Inhibitors
• Anti cancer drug
like bestatin
Efflux transporters
limitation of net
absorption- BA
P-gp-Digoxin(AUC)
Tacolimus(PK)
BCRP
topotecan
Influx Transporters
PEPT1,ASBT,OATP-
B,OATP-D and OATP-E
Efflux Transporters
P-gp,MRP2 or BCRP

41. Intestinal Absorption Contd…

42. HepaticTransporters
Vectorial transport
UPTAKE TRANSPORTER (OATP,OCT(1&3) FAMILY)
EFFLUX TRANSPORTER (MRP2,BCRP,P-GP)

43. HMG-CoA Reductase Inhibitors
uptake- OATP1B1
Efflux-MRP2
Temocapril /ACE inhibitors
Uptake-OATP
Efflux-MRP2
Angiotensin II Receptor Antagonists
Telmisartan-OATP1B3
Valsartan,olmesartan- OATPs 1B1 and 1B3
Efflux-MRP2
Repaglinide and Nateglinide
Repaglinide-OATP1B1
Nateglinide- OATP1B1
HepaticTransporters

44. HepaticTransporters-contd….
Repaglinide and Nateglinide
• Repaglinide is a meglitinide analogue antidiabetic drug.
• It is eliminated by the metabolism mediated by CYPs 2C8 and 3A4
• Transporter-mediated hepatic uptake is one of the determinants of its
elimination rate- OATP1B1
• OATP1B1 is a determinant of its elimination(PK)

45. HepaticTransporters-contd….
Irinotecan
• CPT-11 is a potent anticancer drug
• Intravenous administration of CPT-11, a carboxylesterase converts the drug to SN-
38,an active metabolite.
• SN-38 and SN-38 glucuronide are then excreted into the bile by MRP2, entering the
GI tract and causing adverse effects.
• The inhibition of MRP2-mediated biliary excretion of SN-38 and its glucuronide by
co-administration of Probenecid reduces the drug-induced diarrhea

46. RenalTransporters
• Organic CationTransport
• Organic AnionTransport

47. RenalTransporters Contd….
Organic cation Transport
• Structurally diverse organic cations are secreted
in the proximal tubule.
• Many secreted organic cations are endogenous
compounds ( choline, N-methylnicotinamide,
and DA),
• Organic cation secretion-elimination of
positively charged drugs and their metabolites
(cimetidine, ranitidine, metformin)
• Organic cations appear to cross the basolateral
membrane in the human proximal tubule by two
distinct transporters in the SLC family 22 :OCT2
(SLC22A2) and OCT3 (SLC22A3).

48. RenalTransporters Contd….
• Transport of organic cations from cell to tubular lumen across the apical membrane
occurs through an electro neutral proton–organic cation exchange (protons move
from tubular lumen to cell interior in exchange for organic cations) SLC47 family
/MATE -multidrug and toxin extrusion protein family.
• OCTNs(Bi-functional transporters)
• OCTN1 (SLC22A4) & OCTN2 (SLC22A5)(organic cation flux across the proximal
tubule)
• In the reuptake mode, the transporters function as
• Na+ cotransporters Na+,K+-ATPase (to move carnitine from tubular lumen)
• Na+/K+ exchangers ( antiporters).
• Of the two steps involved in secretory transport, transport across the luminal
membrane appears to be rate limiting

49. RenalTransporters-OCT
OCT2 (SLC22A2)
Proximal, DistalTubules And
Collecting Ducts
• organic cations MPP+ (1-
methyl-4-phenylpyridinium)
• TEA(tetraethylammonium)
OCT3 (SLC22A3)
Intestinal AbsorptionAnd Renal
Elimination
Metformin

50. MATE1 and MATE2-K (SLC47A1, SLC47A2)
apical membrane - proximal tubule.
canalicular membrane - hepatocyte.
• antidiabetic drug metformin
• H2 antagonist cimetidine
• anticancer drug topotecan
• antiviral - acyclovir and ganciclovir.
MATE1
• cephalexin and cephradine
• The herbicide paraquat, a bis-quaternary
ammonium compound that is
nephrotoxic in humans
OCTN1 bidirectional pH- and
ATP-dependent
Transporter
renal transport of gabapentin OCTN2 (SLC22A5)
Na+-dependent carnitine transporter and
an Na+-independent OCT
Mutation- primary systemic carnitine
deficiency

51. RenalTransporters-OAT
• Removal of Xenobiotics from the body
• acidic drugs (e.g., pravastatin, captopril, PAH, and penicillins) and toxins
(e.g., ochratoxin)
• Energetically, hydrophilic organic anions are transported across the
basolateral membrane against an electrochemical gradient, exchanging
with intracellular α-ketoglutarate, which moves down its concentration
gradient from cytosol to blood.

52. OAT1 (SLC22A6)
PAH
PGE2 , urate
cimetidine
OAT2 (SLC22A7)
guanine nucleotides
PGE2
PAH
methotrexate
Cimetidine
OAT3 (SLC22A)
Estrone Sulfate
pravastatin,
cimetidine,
6-mercaptopurine,
methotrexate
OAT4 (SLC22A11).
estrone sulfate ,PAH
zidovudine, tetracycline,
methotrexate
URAT1 (SLC22A12)
urate
MRP2
Glucoronide conjugates
MRP4
Glucuronides
Methotrexate
cyclic nucleotide&
antiviral nucleoside analogues

53. RenalTransporters-contd…
• NPT1, Na+-dependent phosphate transport protein 1 -PAH, probenecid, and
penicillin G.
• BCRP-secretion of Uric acid, XOIs allopurinol and oxypurinol.

54. Transporters-Pharmacodynamics
• Transporters involved in the neuronal reuptake of the neurotransmitters
and the regulation of their levels in the synaptic cleft.
• Transporters - pharmacologic targets for neuropsychiatric drugs
Transporters Substrates
SLC1
(High affinity Glutamate & neutral AA
transporter)
GABA,Glutamate,
MAOTransmitters
Nor epinephrine
Serotonin
dopamine
SLC6
(Na +&cl- dependent neurotransmitter
Transporter)

55. Transporters-PD Contd….
• SLC6 Family(secondary active transporters)
• Reuptake of neurotransmitters into presynaptic neurons
• NorepinephrineTransporter NET(SLC6A2)
• DopamineTransporter DAT (SLC6A3)
• SeratoninTransporter SERT (SLC6A4)
• GABA ReuptakeTransporters GATs (GAT1,GAT2, and GAT3)

56. GABA ReuptakeTransporters(GAT)
Transporters Tissue Inhibitors
GAT1(SLC6A1) Pre-Synaptic membrane of
GABAergic neurons in the brain
Tigabine(Anti-epileptic)
Inh reuptake of GABA-increases
GABA levels in synaptic cleft
GAT2(SLC6A13) CNS-Choroid Plexus & Meninges
Kidney &Liver
Homeostasis of GABA in brain
GAT3(SLC6A11) Glial Cells of Brain Nipetoic acid derivative(anti-
convulsants)

57. NorepinephrineTransporter
Transporter Tissue Function Drugs acting Mutation
NET(SLC6A2) Cental &peripheral
nervous tissue,
Adrenal
chromaffin tissue
Na+ Dependent
reuptake of NE
&DA
Decrese synaptic
dwell time of NE
and terminate its
action
-memory
-mood
Desipramine(selecti
ve inhibitor of NET)
TCAs,Cocaine
Orthostatic
intolerance(famili
al disorder-
abnormal BP &HR
in response to
posture)

58. DopamineTransporter
Transporter tissue Function Drugs acting
DAT(SLC6A3) BRAIN
• Pre-synaptic
membrane of
dopaminergic
neurons
• Along the neurons
away from synaptic
cleft
Reuptake of DA-
terminating its action.
-mood
-behavior
-reward
-cognition
Cocaine and its analogs
Amphetamines
MPTP(Neurotoxin)

59. SerotoninTransporter
Transporter Tissue Function Substrates Drugs acting
SERT(SLC6A4) Brain and peripheral
tissue
Extra-synaptic
axonal membrane
Reuptake and
clearance of
serotonin in the
brain (Na &cl
dependent)
• Serotonin(5-HT)
• Tryptamine
Derivatives
• Neurotoxins
• fenfluramine
SSRIs
Fluoxetine,Paroxetine
TCAs
Amitriptyline

60. Blood -Brain Barrier & Blood –CSF barrier
• Physical barrier-Tight junction, selective permeability
• Metabolic barrier

61. Blood -Brain Barrier & Blood –CSF barrier
SLC family(influx & efflux)
SLC2A1/GLUT1 - glucose,
SLC7A1&SLC7A5/LAT1- amino acids, nucleosides
SLC16A1-metabolic by products lactate and pyruvate
LAT1 (SLC7A5) - l-dopa and gabapentin
SLC22 family (OAT1 and OAT3)
Uptake-β-lactam antibiotics, statins, H2 receptor antagonists.
efflux of xenobiotics from CSF to plasma.
Efflux transporter
Pgp (ABCB1/MDR1)
BCRP and MRP4

62. Blood -Brain Barrier & Blood –CSF barrier
Metabolic barrier
• Circulating catecholamines are inactivated by MAO in the endothelial
cells
• MAO & Dopa Decarboxylase metabolizes L-dopa to 3,4-
dihydroxyphenylacetate(hence the necessity of including a dopa
decarboxylase inhibitor when giving L-dopa to treat Parkinson disease).

63. Transporters Involved In Drug Resistance
1)P-gp
• Overexpressed in tumor cells after exposure to cytotoxic anti-cancer agents
• Pumps out the anti-cancer drugs
2)Breat Cancer Resistance Protein(BCRP)
3)The organic anionTransporters(OAT)
4)Several nucleosideTransporters
5)Overexpression of Multi Drug Resistance Protein(MRP4)-anti-viral nucleoside
analogs

64. MembraneTransporters-Drug Resistance
• Membrane transporters play a critical role in the development of resistance
to
• Anti-Cancer drugs
• Anti-Microbial agents
• Anticonvulsants

65. Novel Approaches to bypass P-gp efflux pump
• Inhibition Of P-gp efflux increases absorption of drugs intracellularly
• Co-administered with therapeutic agents as competitive inhibitors of P-
gp

66. P-gp Inhibitors
P-gp Inhibitors
Reversal agents
Synthetic
polymers
Natural
Polymers
Third
Generation
Second
Generation
First
Generation
Non-selective
/More toxic
• Cyclosporine
• verapamil
Selective/
Less toxic
• Valspodar
• Biricodar
Selective/
Potent
• Tariquidar
• Aosuquidar
• Laniquidar
• Anionic Gums
(xanthan gum)
• GreenTea-polyphenols
• Grapefruit Juice
(D-glucuronic acid)
• Detergents based
on polyethylene
glycol
• Dendrimers
• Thiomers

67. Nano carrier Drug delivery System
• Liposomes-Vesicle made up of phospholipids and
cholesterol enveloping the hydrophilic aqeous solution
Others
• Niosomes-Vesicle made up of surfactants with/without
cholesterol
• Dendrimers
• Polymeric Nanoparticls
• Polymer Drug Conjugate(Albumin conjugated with
Paclitaxel-Ambraxane)

68. CONCLUSION
• Transporters are membrane proteins present in all organisms.
• These proteins control the influx of essential nutrients and ions and the efflux of
cellular waste, enviorment toxins and other xenobiotics
• Transporters play a vital role in Absorption,distribution,elimination,therapeutic
effect and adverse effect of drugs
• Transporters play a critical role in development of resistance to anti-cancer, anti-
viral, anticonvulsant drugs
• Transporters are important in evaluation and development of newer drugs