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INTRODUCTION
Targeted drug delivery is a strategy that selectively and preferentially delivers the
therapeutic agents to the target site concurrently failing access to the nontarget site.
Need of
TDDS
Pharmaceutical
Reasons
Low solubility
Drug instability
Pharmacodynamic
Reasons
Low specificity
Low therapeutic index
Pharmacokinetic
Reasons
Poor absorption
Short t1/2
Large Vd
6. • Drug delivery to brain
is the process of
passing therapeutically
active molecule across
the Blood Brain barrier
for the purpose of
treating brain maladies.
• This is a complex
process that must that
must take into the
account the complex
anatomy of the brain as
well as the restrictions
imposed by the special
junctions of the Blood
Brain Barrier.
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Schematic Representation of Transport Routes across the BBB
Source: J. Kim et al. / Journal of Industrial and Engineering Chemistry 73 (2019) 8–18.
8. • Carrier is one of the special molecule or system essentially required for effective transportation of
loaded drug up to the pre selected sites.
• They are engineered vectors, which retain drug inside or onto them either via encapsulation and/or via
spacer moiety and transport or deliver it into vicinity of target cell.
Ideal Properties of Carriers
• Should be non-toxic, non-immunogenic, non-inflammatory, biocompatible and biodegradable.
• Particle size should be < 200 nm and should have a narrow particle size distribution.
• Should be physically stable in blood circulation (i.e. no aggregation and dissociation).
• Should avoid opsonisation for longer circulation time in blood.
• Should possess BBB-targeted moiety coupled for delivery across BCECs via receptor- or adsorptive-
mediated transcytosis.
• Tunable drug release profiles.
• Production process of NPs should be scalable and cost effective.
• Should be applicable to carry antibodies, peptides, proteins,
• nucleic acids, sugars or small molecules.
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9. Pharmaceutical Carriers
1. Microcapsules
2. Microparticles
3. Lipid based nanoparticles
I. Liposomes
II. Solid lipid nanoparticles (SLNs)
III. Nanostructured lipid carriers (NLCs)
4. Polymer based nanoparticles
I. Polymeric nanoparticles
II. Polymeric micelles
III. Dendrimers
IV. Polymeric nanogels
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1. Microcapsules
Multilayer of lipid
API
Open Multilayers of lipid surrounding API
Morphologies of different microencapsulated
Mononuclear Polynuclear
Matrix Multifim
Source: Jurkowska and Szczygiel, 2016
Fundamental Considerations
1. Nature of Core Materials
2. Coating Materials
3. VehicleSource: Beautynewsindia.com
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2. Microparticles
(a) Mononuclear/single core/core-shell (b) Multi-wall (c) Polynuclear/multiple core (d) Matrix (e) Coated polynuclear core (f) Coated
matrix particle (g) Patchy microparticle (h) Dual-compartment microcapsule (i) Colloidosome (j) Giant liposome
Spherical Microparticles
NonSpherical Microparticles
k) Irregular-shaped microparticle (l) Torus-shaped microparticle
(m) Tullet-shaped microparticle (n) Microtablet (o) Cubic-shaped
microparticle
• An advantage of microcarriers over nanoparticles is that they
do not traverse into the interstitium over the size of 100 nm
transported by the lymph, and thus act locally.
• In the case of multiparticulates, the dose is distributed in many
small separate particles, which carry and liberate a part of the
dose, hence the malfunction of an individual subunit does not
cause the failure of the whole dosage.
Source: Miléna Lengyel, et.al, Review “ Microparticles, Microspheres, and
Microcapsules for Advanced Drug Delivery”, Sci. Pharm. 2019, 87, 20;
doi:10.3390/scipharm87030020
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3. Lipid-Based Nanoparticles
Source: Sarkar Alika, et. al, “Nanoparticles as a Carrier System for Drug Delivery Across Blood Brain Barrier”, Current Drug Metabolism, 2017, Vol. 18, No. 00.
A. Liposomes B. Solid Lipid NPs C. Nanostructured Lipid Carrier
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3. Polymer-Based Nanoparticles
A. Nanospheres B. Nanocapsules C. Polymeric
Micelles
D. Dendrimers E. Polymeric
Nanogels
Source: Sarkar Alika, et. al, “Nanoparticles as a Carrier System for Drug Delivery Across Blood Brain Barrier”, Current Drug Metabolism, 2017, Vol. 18, No. 00.
18. Effective treatment for almost all the brain disorders continues to be one of the most significant
challenges of modern medicine due to the presence of BBB which impedes the delivery of many
therapeutic drugs.
Recent breakthroughs in the field nanotechnology provide an appropriate solution to problems
associated with delivery approaches and thus can be effectively used to treat a wide variety of brain
disorders.
Currently, various brain delivery nanocarrier systems with different features are available, facilitating
the delivery of neuroactive drugs including genes, growth factors, etc. to the brain.
NPs offer various advantages over the traditional delivery of drugs like- minimized side effects,
increased drug half-life time, extended or controlled drug release, decreased drug dose and the
possibility to enhance drug crossing across the BBB.
Even though nanotechnology-based applications have great potentials, there are several concerns
about their undesirable effects on human health and environment.
Thus while developing any therapeutic drug, very careful attention should be given to toxicity and
extensive studies should also be made for determining its efficacy and safety in humans.
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CONCLUSION
19. Nanotechnology is a rapidly emerging technology and it is widely expected that over the next couple of
years, it will continue to expand and evolve in various areas of life science research and each
advancement in the science of Nano-biotechnology will help us to unravel the mystery of drug delivery
across the BBB. There are many technological challenges to be met, for targeted brain drug delivery:
• The toxicity of NPs and their degradation products remain a key concern and ought to be addressed
before applying them to human patients.
• Improvement/enhancement of NPs release from implantable devices/ nanochips or multi reservoir
drug delivery-chips.
• Nanoparticles for tissue engineering.
• Encapsulation of implants by NPs containing biodegradable polymer for sustained release.
• Development of Theranostic NPs that are engineered NPs with combined therapeutic and diagnostic
applications.
• Development of multifunctional NPs for simultaneous targeting, imaging and treatment, will
encourage further development of nanomedicine in the next decade.
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FUTURE PROSPECTS
20. 1. Miléna Lengyel, et.al, Review “ Microparticles, Microspheres, and Microcapsules for Advanced
Drug Delivery”, Sci. Pharm. 2019, 87, 20; (Doi:10.3390/scipharm87030020)
2. Md. Sahab Uddin, Mst. Marium Begum, Carriers for Brain Targeting: Recent Advances and
Challenges, August 2019. (DOI: 10.1201/9780429465079-1)
3. Huile Gao, Perspective on Brain Targeted Drug Delivery Systems. 2018. (Doi: 10.1016/B978-0-12-
814001-7.00018-4)
4. Sarkar Alika, et. al, “Nanoparticles as a Carrier System for Drug Delivery Across Blood Brain
Barrier”, Current Drug Metabolism, 2017, Vol. 18, No. 00.
5. Yasir et al. / IJBMSP, Vol. 5, No. 1, pp. 32-40, June 2015.
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REFERENCES
