The presentation aims at providing detailed knowledge about the transport mechanisms involved for delivering drugs and genes of interest inside the body, across the biological membranes.
14. biology4alevel.blogspot.com
•Diffusion across membrane is
decided by size of the molecule
as well as its solubility in
lipids.(as lipids are the major
components of the blayer).
•The lipid bilayer is permeable
to a few small, uncharged,
molecules like
oxygen (O2) and carbon dioxide
(CO2).Thus , they simply move
across through diffusion.
•Ions and hydrophilic moiety
finds it difficult to move across
and thus have protein which
provide sites for such molecules
but, in the presence of a
concentration gradient,(since
ATP is not used)
17. geoweeks.blogspot.com
Symporters
•SGLT1 - Na+ /glucose symporter in gut epithelia.
• Important for transport of nutrients through intestinal epithelium.
• Amino acids are transported in similar manner
18. Antiporters
•NHE-1 - Na+/H+ antiporter in kidney and gut epithelia for regulation of
systolic blood pressure.
•3Na+/Ca2+ antiporter in the heart for regulation of heart contractility.
20. •Examples : leucocytes,
neutrophils, and
monocytes can engulf
foreign substances like
bacteria .
•Also used in case of cell
migration and adhesion
related functions.
•Examples : The uptake of
extracellular fluids such as
hormones and enzymes by the
body cells
•The human egg cell takes up
the nutrients present in the
surrounding environment
secreted by the other cells.
•Uptake of nutrients by the cells
containing microvilli present in
the intestine.
•Examples :
Neurotransmitters
released from the neuron
cells.
•Secretion of pancreatic
digestive enzymes
•Repairing wounds of the
plasma membrane
academic.brooklyn.cuny.edu
21.
22. • Drugs is "a chemical substance used in the treatment, cure,
prevention, or diagnosis of disease or used to otherwise
enhance physical or mental well-being”
• This chemical substance can be polar (hydrophilic), non-
polar (hydrophobic) and small or large in size.
23. • Drugs is "a chemical substance used in the treatment, cure,
prevention, or diagnosis of disease or used to otherwise
enhance physical or mental well-being”
• This chemical substance can be polar (hydrophilic), non-
polar (hydrophobic) and small or large in size.
• Drug’s transport across the membrane usually takes place
through facilitated diffusion or receptor mediated delivery.
• Exchange of these chemicals also occur by active transport
or other transport mechanisms depending upon the
chemical nature of the drug and the target organ.
24. fearmastery.wordpress.com
First
There are several barriers lining the organs which do not allow
passage of the drug molecules or gene containing molecules
simply through diffusions or active transports.
Second
Specific delivery of drug or gene to the targeted organ.
Third
Keeping the normal cells (un diseased) out of contact of the drug
action or exposure to chemicals that the drug contains
26. The word ”trans fection” is a blend of trans- and infection.
Genetic material (such as super coiled plasmid
DNA or siRNA constructs), or even proteins such as antibodies,
may be transfected.
27. Transformation is the genetic alteration of a cell resulting from the
direct uptake and incorporation of exogenous genetic material
(exogenous DNA) from its surroundings and taken up through the cell
membrane(s).
28. Transformation is the genetic alteration of a cell resulting from the
direct uptake and incorporation of exogenous genetic material
(exogenous DNA) from its surroundings and taken up through the cell
membrane(s).
29. Transformation is the genetic alteration of a cell resulting from the
direct uptake and incorporation of exogenous genetic material
(exogenous DNA) from its surroundings and taken up through the cell
membrane(s).
Transfection is specifically used
for eukaryotic cells.
Transformation is the broader
term used for both prokaryotes
as well as eukaryotes.
30. Transformation is the genetic alteration of a cell resulting from the
direct uptake and incorporation of exogenous genetic material
(exogenous DNA) from its surroundings and taken up through the cell
membrane(s).
Transfer of gene , drug or any
macromolecule into an
eukaryotic cell is transfection
Transfer of gene of interest into
any cell can be termed as
transformation.
31. Transformation is the genetic alteration of a cell resulting from the
direct uptake and incorporation of exogenous genetic material
(exogenous DNA) from its surroundings and taken up through the cell
membrane(s).
Transfer is done typically
through non viral methods.
Transfer is done usually with a
viral vector or carrier.
32.
33. *Electroporation—the use of high-voltage
electric shocks to introduce DNA into cells.
**It is a procedure that is gaining in
popularity for standard gene transfer and also
allows the generation of genetically modified
mice.
***It can be used with most cell types, and,
because it requires fewer steps, can be easier
than alternate techniques.
****It can be used for in vivo gene transfer
particularly for surface or near surface tissue
such as skin, muscle and certain tumors or
even internal tissues such as liver.
www.bio-rad.com
34. •Induction of membrane pores using ultrasound is exploited to
facilitate entry of proteins, nucleic acids and drugs into the cell.
www.intechopen.com
•The microbubbles consist of lipid shell and perfluorocarbon gas on the
inside. The plasmid gene to be delivered resides in the shell.
35. •Induction of membrane pores using ultrasound is exploited to
facilitate entry of proteins, nucleic acids and drugs into the cell.
www.intechopen.com
•The microbubbles consist of lipid shell and perfluorocarbon gas on the
inside. The plasmid gene to be delivered resides in the shell.
• After infusing the microbubbles with pDNA intravenously, they are
detected in the target organ by echography.
•Under ultrasound exposure, the microbubbles burst and the energy
creates transient pores in membranes of surrounding cells, and pDNAs
are inserted into the cells
37. •Microinjection is a well established technique used routinely for injection of
animal cells, tissues and embryos to insert genetic material such as DNA, RNA,
proteins and macromolecules directly into animal cells or embryos a cell
cytoplasm or nucleus.
•Genetic material is inserted via a needle which penetrates the cell membrane
and/or the nuclear envelope.
thegeneticsofpikachu.weebly.com
38. •Use of a gene gun directly shoots a piece of DNA into the
recipient plant tissue.
• Tungsten or gold beads are coated in the gene of interest and
fired through a stopping screen, accelerated by Helium, into the
plant tissue.
•The particles pass through the plant cells, leaving the DNA
inside.
www.bio-rad.com
39. This method also alters the permeability of the cell membrane:
• Ca2+ interacts with the negatively charged phospholipid heads of the
cell membrane, creating an electrostatically neutral situation.
• Lowering the temperature stabilizes the membrane, making the
negatively charged phosphates easier to shield.
• Then a heat shock creates a temperature imbalance and thus a
current, which helps get the DNA into the cell.
41. fearmastery.wordpress.com
•Development of drug delivery systems
for brain delivery is one of the most
challenging research topics in
pharmaceutical areas.
•This is mainly due to the presence of
the blood-brain barrier (BBB), which
separates the blood from the cerebral
parenchyma thus limiting the brain
uptake of the majority of therapeutic
agents.
42. •It is a highly selective permeability barrier that separates the circulating blood from
the brain extracellular fluid (BECF) in the central nervous system (CNS).
• It is formed by capillary endothelial cells, which are connected by tight
junctions with an extremely high electrical resistivity.
•It allows the passage of water, some gases, and lipid soluble molecules by passive
diffusion, as well as the selective transport of molecules such as glucose and amino
acids that are crucial to neural function.
•It prevents the entry of lipophilic, potential neurotoxins from reaching to brain.
43. •It should be controlled and not damage the barrier.
•Drug should be biodegradable, specific and not toxic.
•The drug load transported through the BBB should be adequate
for reaching therapeutic concentrations in the brain.
•Therapeutic concentrations should be maintained for a sufficient
duration of time for the desired efficacy.
Characteristics of ideal drug delivery across
the BBB
44. Liposome = “lipos”(means fat) + “soma” (means body)
When lipids are placed in contact with water, the unfavorable
interactions of the hydrophobic segments of the molecule with the
solvent result in the self assembly of lipids, often in the form of
liposomes.
icanhasscience.com
46. **Hydrophobic drugs place themselves inside the bilayer of the liposome
and hydrophilic drugs are entrapped within the aqueous core or at the
bilayer interface.
47. **Liposomes can be surface functionalized to enable movement through
PEGylation and to promote receptor-mediated endocytosis by using targeting
ligands such as antibodies, peptides, proteins, carbohydrates, and various other
small molecules.
48. **Chemotherapeutics or diagnostics can be encapsulated into the aqueous
lumen, incorporated into the lipid bilayer, or conjugated to the liposome
surface.
49. ***Polyethylene glycol (PEG) density determines its structure at the liposome
surface.
Densities below 9% -> a mushroom-like globular structure
above 9% -> a more rigid, extended, brush-like morphology.
50. *Liposomes are composed of biodegradable, biologically inert and
non-immunogenic lipids.
*They produce no pyrogenic or antigenic reactions and
possess limited toxicity .
*The ease of surface modification to bear the targetable
properties make liposomes widely acceptable.
51. *The entrapment of the drugs, both hydrophilic and
hydrophobic, into the liposomes is used to bypass the frequent
generic toxicity associated with the drug as often seen in cancer
drugs
*The modification of liposomes permits a passive or active
targeting of the tumor site.
*Specific modification effect enables an efficient drug payload
into the malignant cell of tumors, while the non-malignant
cells become minimally impacted.
52. *Regenerative Medicine and Tissue Engineering for the Treatment of
Diabetes
By Matsumoto S, SoRelle JA and Shimoda M
DOI: 10.5772/22808
*Transfection by Electroporation
Huntington Potter, Ph.D. and Richard Heller, Ph.D.
*Gene Therapy for Cardiovascular Disease Mediated by Ultrasound
and Microbubbles
Zhi-Yi Chen, Yan Lin, Feng Yang, Lan Jiang, Shu ping Ge
DisclosuresCardiovasc Ultrasound. 2013;11(11)
53. *Nanobiotechnology-Based Strategies for Crossing the Blood–Brain
Barrier
Kewal K Jain
*Drug transport across the blood–brain barrier
William M Pardridge
*Liposomes as Potential Drug Carrier Systems for Drug Delivery
Melis Çağdaş1, Ali Demir Sezer2 and Seyda Bucak3
*http://www.btxonline.com/categories/M
icroinjection/
Short interfering rna is the ds rna for rna used in rna interfering techniques for silencing of the disordered gene or disease causing gene.
Perfluoro carbon gas is filled
Perfluoro carbon gas is filled
Perfluoro carbon gas is filled
Astocytes : provision of nutrients to the nervous tissue, maintenance of extracellular ion balance, and a role in the repair and scarring process of the brain and spinal cord following traumatic injuries.
Pericytes :  Pericytes regulate capillary blood flow, the clearance and phagocytosis of cellular debris, and the permeability of the blood–brain barrier.
Also maintains homeostatis.