DRUG DELIVERY SYSTEMS

DRUG DELIVERY
Presented by:
Wasim Nawaj
Ashwini Kumar
Sunil Kumar Patel
Rohan Jena
Department of Chemistry
IIT GUWAHATI 1

Contents
 Introduction
 Conventional and novel drug delivery methods
 Peptide drug delivery system
 liposome drug delivery system
 nanocomposite drug delivery system
 conclusion
2

Introduction
 Drug delivery refers to approaches, formulations, technologies, and systems for
transporting a pharmaceutical compound in the body as needed to safely achieve
its desired therapeutic effect.
3

Conventional drug delivery
systems
Drug delivery systems
Novel drug delivery system
(NDDS)
Oral
Buccal and Sublingual
inhalation
Dermal, Transdermal
Injection
liposomes
niosomes
Peptides and Proteins
nanoparticles
Nanocomposites 4

Oral
Fig. oral drug delivery
5

Buccal and sublingual drug administration
Fig. Buccal drug delivery Fig. sublingual
6

Inhalation and Transdermal
Fig. inhalation Fig. transdermal
7

Novel Drug Delivery Systems
 Advantageous over convensional methods
 Involves medicinal devices
 Provides greater safety
 target a drug specifically to a desired tissue
 Improves drug potency
 Controlled drug release
Modes of NDDS
 Targeted drug delivery system
 Controlled drug delivery system
 Modulated drug delivery system
Fig. targeted drug delivery system 9

LIPOSOMES
TARGETED DRUG DELIVERY
11

LIPOSOMES
Liposomes are tiny bubbles (vesicle), in which an aqueous volume is entirely
enclosed by a Phospholipid bilayer molecules
Firstly produced by D. Bangham (1964)
Size of Liposome: 20 nm - ~3 µm range
12

MECHANISM OF LIPOSOME
FUNCTIONING
13

TARGETED DRUG DELIVERY VIA LIPOSOME
THE FOLLOWING STEPS INVOLVE:-
1. Encapsulation of drug molecule.
2. Transportation of liposome to the
Target.
3. Fusion of liposome to the cell
membrane.
4. Release of Drug molecule.
ref: Science live magazine
14

WAYS OF DRUG DELIVERY SYSTEM
1. CONVENTIONAL LIPOSOME
These are first generation of liposomes, consist of cationic, anionic or neutral
phospholipids.
2. STERICALLY-STABILIZED LIPOSOMES
Attachment of hydrophilic polymer (e.g. poly-ethylene glycol, PEG), which
improves the efficacy of encapsulated agents
3. LIGAND-TARGETED LIPOSOMES
Offer a site-specific delivery of drugs to organs in vivo (inside living organisms)
4. THERANAUSTIC LIPOSOMES
A single system consist of nanoparticle, a targeting element, an imaging
component and a therapeutic component
(L. Sercombe, Frontiers in Pharmacology, 6, 2015)
15

FIGURE : Schematic representation of the different types of liposomal drug delivery systems 16

1. Liposomes are biocompatible, completely biodegradable, non-toxic
and flexible.
2. Liposomes have both a lipophilic and aqueous environment making it
useful for delivering hydrophobic, amphipathic, and hydrophilic
medicines.
3. Liposomes with their layers encapsulates the drug and serves as a
protection of the drug from the environment as well as acting as a
sustained release mechanism.
4. Liposomes are also used in gene therapy.
17
ADVANTAGES

PEPTIDE DRUG DELIVERY SYSTEMS
Peptide – These are short polymers of amino acid (monomers) linked by peptide
bonds .
18

Targeted Delivery of Cell Penetrating Peptide
Virus-like Nanoparticles to Skin Cancer Cells
• The main aim of this study was to screen for a cell penetrating peptide (CPP) for
the development of a targeting vector for skin cancer. In this study, we identiied
a CPP with the sequence NRPDSAQFWLHH from aphage displayed peptide
library.
• This CPP targeted the human squamous carcinoma A431 cells through an
interaction with the epidermal growth factor receptor (EGFr).
• Methyl-ß-cyclodextrin (MßCD) and chlorpromazine hydrochloride (CPZ)
inhibited the internalisation of the CPP into the A431 cells, suggesting the
peptide entered the cells via clathrin-dependent endocytosis.
• The CPP displayed on hepatitis B virus-like nanoparticles (VLNPs) via the nanoglue
successfully delivered the nanoparticles into A431 cells. The present study
demonstrated that the novel CPP can serve as a ligand to target and deliver VLNPs
into skin cancer cells. 19

Subtraction biopanning for the selection of A431 cell penetrating peptides (CPPs).
TABLE 1: Enrichment of phages in three rounds of
biopanning
Table 2 : phages that internalized A431 cells and their CPPs
obtained from three rounds of biopanning
20
Bee Koon Gan1, Chean Yeah Yong1, Kok Lian Ho2, Abdul Rahman Omar1,3, Noorjahan Banu Alitheen 1,4 & Wen Siang Tan 1 Sci Rep. 2018; 8: 8499

Fig. Analysis of internalization of phage clone into A431 & NHDF cells with immunofluorescence
microscopy 21

Active energy-dependent uptake of phage NRPDSAQFWLHH by A431 cells.
Immunofluorescence microscopic analysis. Purified phage carrying the peptide
NRPDSAQFWLHH was added to A431 cells and incubated separately at 4 and 37° C.
22

Fusion phage and peptide NRPDSAQFWLHH competitive assay, and
selective internalization of the peptide into A431 cells
Synthetic peptide NRPDSAQFWLHH internalises A431 cells. A431 and NHDF cells were incubated with
fluorescein-labelled peptide NRPDSAQFWLHH at 37 °C for 16 h
23

Efect of endosomal inhibitors on the entry
of peptide NRPDSAQFWLHH into A431 cells.
Fig. A431 cells were pre-incubated with different
endosomal inhibitors, and in the presence of
fluorescein-labelled peptide NRPDSAQFWLHH.
24

Peptide NRPDSAQFWLHH internalises A431 cells via epithelial growth factor receptor (EGFr).
Cetuximab inhibits internalisation of peptide into A431 cells. Fluorescein-labelled peptide NRPDSAQFWLHH was
added into A431 cells and incubated at 37 °C for 16 h in the presence and absence of anti-EGFr (Cetuximab 225;
10 μg/mL). 25

Conjugation of peptide onto tHBcAg VLNPs and delivery of the nanoparticles into A431 cells.
SDS-PAGE of tHBcAg conjugated to peptide NRPDSAQFWLHHGGGSLLGRMKGA. Lanes M: molecular mass markers(kDa),
26

Delivery of tHBcAg VLNPs conjugated to peptide NRPDSAQFWLHHGGGSLLGRMKGA into A431 cells.
27

Nanoscience and drug delivery
- small particles for big problems
28

 Nanocomposites are broad range of materials consisting of two or more components
with at least one component having dimension in the nm range.
 In composite materials, one phase is usually continuous and called the matrix, while the
other phase called the dispersed phase.
 i.e Nano sized particles (metals/semiconductors/dielectrics etc) embedded in different
matrix materials (ceramics/glass/polymers).
Why nanocomposites ?
 Exhibit different (often enhanced) properties than the individual components
 Electrical, magnetic,
 electrochemical,
 catalytic, optical,
 structural, and
 mechanical properties
Nanocomposites
29

Figure : Iron ﬂuoride–graphene nanocomposites for LIB
cathode materials , J. Mater. Chem. A,2014,2,15
Nanoparticle
Matrix
nanocomposite
The term ‘‘nanocomposite’’ is commonly adopted to refer to polymers that contain dispersed
nanofillers with an average particle size of less than 100 nm
30

Nanoparticle vs Nanocomposite
In cases where the nanoparticle could induce an undesired biological response, the
nanocomposite can prevent the direct interaction of the nanoparticle with the
biological system.
Example :
 The Ag nanoparticles can be considered as strong antibacterial agents.
 The toxicity of Ag ions affected the basic metabolic cellular functions common to all
specialized mammalian Cells.
 But embedding them in a polymer matrix may reduce their cytotoxic effects, with
enhancing the properties of polymer matrix, without any change in antimicrobial
property of Ag.
31

Fig. UV-vis spectra of various amounts of Ag nanoparticles
(a) in distilled water and (b) chitosan solution.
Macromol. Biosci. 2008, 8, 932–941 2008 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
32
a
b Fig. Inverse microscopic images of L929 cells cultured on
surfaces of (c) uncoated glass slide; (d) pure GC film; (e)
GC/Ag 50 and (f) GC/Ag 200 nanocomposites after a 72 h
culture.
c d
fe

Hydrogel Nanocomposites
Remotely Controlled Drug Delivery System
 Hydrogels are 3D hydrophilic polymers that do not dissolve but can swell in water or can
respond to the fluctuations of the environmental stimuli.
 Highly absorbent (they can contain over 90% water)
 Both solid like and liquid like properties
 High biocompatibility (as mostly contains water)
NANO-PARTICLE STIMULI
Fe3O4 (Magnetic) Alternating Magnetic Field
Au Near IR
Carbon nano-tubes (CNTs) Radio frequency
33

Drug vehicle Drug Target site
Drug loaded
transportation
Drug vehicle attached to
target site
34

Dispersed nanoparticle - magnetic iron oxide (Fe3O4)
Polymer matrix - N-isopropylacrylamide (NIPAAm)
Stimuli foor drug release- AMF
Fig. Different forms of hydrogel nanocomposites: bulk nanocomposites, particle nanocomposites, and core-shell nanocomposites
Soft Matter, 2010, 6, 2364–2371 Nitin S. Satarkar, Dipti Biswal and J. Zach Hilt
NIPAAm-Fe3O4 Nanocomposite
AMFs are minimally absorbed by
tissue, the use of these fields for RC
materials and devices is attractive for
in vivo applications.
35

Fig. A schematic of AMF-induced
heating, collapse, and squeezing effects
The release profile of Vitamin B12 for multiple AMF cycles
Soft Matter, 2010, 6, 2364–2371 Nitin S. Satarkar, Dipti Biswal and J. Zach Hilt
36

37
NDDS have several advantages over convention drug delivery methods.
 It reduces the side effects to the healthy tissues and cells.
 It specifically targets the infected issues/cells.
 Controlled and moduled release of drugs for prolonged interval of time
 Lower rate of degradation of drug and drug carrier
CONCLUSION

DRUG DELIVERY SYSTEMS

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