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Current
Drug Delivery
ISSN: 1567-2018
Current Drug Delivery
Volume 5, Number 3, July 2008
Contents
Pharmacogenetics of Intestinal Absorption Pp.
153-169
Tsutomu Nakamura, Motohiro Yamamori and
Toshiyuki Sakaeda
[Abstract]
Self-Nanoemulsifying Drug Delivery System for
Enhanced Bioavailability and Improved Hepatoprotective Activity
of Biphenyl Dimethyl Dicarboxylate Pp. 170-176
Hanan M. El-Laithy
[Abstract]
Sustained Release from Mesoporous Nanoparticles:
Evaluation of Structural Properties Associated with Release
Rate Pp. 177-185
Ulrika Brohede, Rambabu Atluri, Alfonso E. Garcia-Bennett
and Maria Strømme
[Abstract]
Colon Targeted Drug Delivery Systems -An Overview
Pp. 186-198
P. Kumar and B. Mishra
[Abstract]
Elastic Liposomes Mediated Transdermal Delivery
of An Anti-Jet Lag Agent: Preparation, Characterization and
In Vitro Human Skin Transport Study Pp. 199-206
Vaibhav Dubey, Dinesh Mishra, Manoj Nahar and
N.K. Jain
[Abstract]
Elastic Liposomes Bearing Meloxicam-β-Cyclodextrin
for Transdermal Delivery Pp. 207-214
Sanjay K. Jain, Yashwant Gupta, Anekant Jain
and Sadia Amin
[Abstract]
Methotrexate Bearing Calcium Pectinate Microspheres:
A Platform to Achieve Colon-Specific Drug Release Pp.
215-219
M. Chaurasia, M.K. Chourasia, Nitin. K.
Jain, A. Jain, V. Soni, Y. Gupta
and S.K. Jain
[Abstract]
Floating Microspheres as Drug Delivery System:
Newer Approaches Pp. 220-223
Sunil K. Jain, Govind P. Agrawal and Narendra
K. Jain
[Abstract]
Stem Cell Implantation for Myocardial Disorders
Pp. 224-229
Kenichi Yamahara and Noritoshi
Nagaya
[Abstract]
Abstracts
[Back to top]
Pharmacogenetics of Intestinal Absorption
Tsutomu Nakamura, Motohiro Yamamori and
Toshiyuki Sakaeda
The small intestine is the primary site of absorption
for many drugs administered orally and so is the target tissue
for pharmacotherapeutic strategies to control the oral absorption
of drugs. Drug transporters, including the ATP-binding cassette
(ABC) superfamily and the solute carrier (SLC) superfamily,
have been considered to play a physiological role in regulating
the absorption of xenobiotics, and variations in their expression
level and function in the small intestine cause intra- and
inter-individual variation in the oral absorption of drugs.
Recent advances in molecular biology have suggested that genetic
polymorphisms are associated with the expression level and
function, and thereby inter-individual variation. In this
review, the pharmacogenetics of these transporters is summarized,
and their future significance in the clinical setting is discussed.
[Back to top]
Self-Nanoemulsifying Drug Delivery System for Enhanced
Bioavailability and Improved Hepatoprotective Activity of
Biphenyl Dimethyl Dicarboxylate
Hanan M. El-Laithy
Biphenyl Dimethyl Dicarboxylate (BDD) is insoluble in
aqueous solution and the bioavailability after oral administration
is low. Self-nanoemulsifying drug delivery system (SNEDDS)
containing BDD has been successfully prepared using carefully
selected ingredients which are less affected by pH and ionic
strength changes to improve its bioavailability. SNEDDS is
an isotropic mixture of lipid, surfactant, and cosurfactant
which are spontaneously emulsified in aqueous medium under
gentle digestive motility in the gastrointestinal tract. Pseudo
ternary phase diagrams composed of various excipients were
plotted to identify self –nano -emulsifying area. Droplet
size changes upon dilution with aqueous media and in vitro
release of BDD from SNEDDS in 0.1N HCl and phosphate
buffer (pH 7.4) were studied and compared with commercial
chinese pilules® and Pennel capsules®
. The hepatoprotective activity upon oral administration of
SNEDDS against carbon tetrachloride-induced oxidative stress
in albino rats was assessed by measuring biochemical parameters
like serum glutamic oxalacetate transaminase (SGOT), serum
glutamic pyruvate transaminase (SGPT) and lactate dehydrogenase
(LDH).
Results showed that using a proper ratio of Tween 80 to Transcutol
as surfactant and co-surfactant respectively and Miglyol 812
as oil to surfactants mixture resulted in production of infinitely
diluted formulations in nano droplet size range. BDD self
nano emulsified formula composed of 20% Miglyol 812 , 60%
Tween 80 and 20% Transcutol released 99% of the drug very
rapidly within 10-15 minutes regardless of the pH condition.
The oral absorption and bioavailability of BDD self nano emulsified
formula in albino rats were significantly enhanced (P<
0.01) with an average improvement of 1.7 and 6-folds that
of commercial chinese pilules® and Pennel capsules®
respectively. This improvement was also confirmed histopathologically
in chemically injured rats and by the significant decrease
in elevated liver enzymes level.
[Back to top]
Sustained Release from Mesoporous Nanoparticles: Evaluation
of Structural Properties Associated with Release Rate
Ulrika Brohede, Rambabu Atluri, Alfonso E. Garcia-Bennett
and Maria Strømme
We present here a detailed study of the controlled release
of amino acid derived amphiphilic molecules from the internal
pore structure of mesoporous nanoparticle drug delivery systems
with different structural properties; namely cubic and hexagonal
structures of various degrees of complexity. The internal
pore surface of the nanomaterials presented has been functionalised
with amine moieties through a one pot method. Release profiles
obtained by Alternating Ionic Current measurements are interpreted
in terms of specific structural and textural parameters of
the porous nanoparticles such as pore geometry and connectivity.
Results indicate that diffusion coefficients are lower by
as much as four orders of magnitude in 2-dimensional structures
in comparison to 3-dimensional mesoporous solids. A fast release
in turn is observed from mesocaged materials AMS-9 and AMS-8
where the presence of structural defects is thought to lead
to a slightly lower diffusion coefficient in the latter. Amount
of pore wall functionalisation and number of binding sites
on the model drug are found to have little effect on the drug
release rate.
[Back to top]
Colon Targeted Drug Delivery Systems -An Overview
P. Kumar and B. Mishra
In the last two decades colon targeted drug delivery
has gained increased importance not just for the deliver drugs
for the treatment of various colonic diseases but also for
its potential for delivery of proteins and therapeutic peptides.
In the past various traditional approaches used for colon
targeted delivery like prodrugs, pH, time dependent, and microflora
activated systems, have achieved limited success. For successful
colon targeted drug delivery, the drug needs to be protected
from absorption and/or the environment of the upper gastrointestinal
tract and then be abruptly released into the colon. Hence
continuous efforts have been made on designing colon targeted
drug delivery systems with improved site specificity and versatile
drug release kinetics to fulfill different therapeutic needs.
In last couple of years few new systems have been developed
for colon targeted drug delivery such as pressure dependent
systems, CODESTM technology,
micrsponges, pectin and galactomannan coating, microbially
triggered osmotic systems, lectins and neoglyconjugated etc.
which are reported to have better in-vivo site specificity
and design rationale than the earlier approaches. This review
article gives an overview of various approaches for colonic
targeted drug delivery with emphasis on newer systems, their
merits and demerits, in vitro/ in-vivo evaluation
and market status of such delivery systems.
[Back to top]
Elastic Liposomes Mediated Transdermal Delivery of
An Anti-Jet Lag Agent: Preparation, Characterization and In
Vitro Human Skin Transport Study
Vaibhav Dubey, Dinesh Mishra, Manoj Nahar and
N.K. Jain
In order to get across the intact skin, drug-laden carriers
have to pass through narrow, confining pores of 50 nm or less
diameter, under the influence of a suitable transdermal gradient.
Novel ultradeformable carriers, the elastic liposomes achieve
this target via its deforming and self-optimizing property.
The main goal of this work was to prepare and characterize,
elastic liposomes bearing melatonin, an anti-jet lag agent
for its efficient transdermal delivery. Elastic liposomes
bearing melatonin were prepared by modified extrusion method
and characterized for shape, lamellarity, size distribution,
percent drug loading, turbidity profile by Transmission electron
microscopy (TEM), Dynamic light scattering (DLS), Mini-column
centrifugation and Nephelometric techniques. The effect of
different formulation variables like type of surfactant and
concentration of surfactant on the deformability of vesicles,
turbidity changes, transdermal flux across human cadaver skin,
amount of drug deposited into the skin were investigated.
Confocal laser scanning (CLS) micrographs revealed that probe
(Rhodamine Red) loaded elastic liposomes were able to penetrate
much deeper than the probe loaded conventional rigid liposomes.
Out of the three surfactants utilized namely, Span 80, Sodium
cholate and Sodium dodecylsulphate, formulation bearing Span
80 at an optimum lipid: surfactant ratio of 85:15% w/w proved
to be the best in all parameters studied. The optimum skin
permeation profile including greater transdermal flux and
lower lag time of melatonin from optimized elastic liposomes
via human cadaver skin was observed. Our results of the present
study demonstrated the feasibility of elastic liposomal system
for transdermal delivery of this anti- jet lag agent, which
provides better transdermal flux, higher entrapment efficiency,
greater skin drug deposition and possesses the ability of
a self-penetration enhancer as compared to conventional liposomes.
[Back to top]
Elastic Liposomes Bearing Meloxicam-β-Cyclodextrin
for Transdermal Delivery
Sanjay K. Jain, Yashwant Gupta, Anekant Jain
and Sadia Amin
The ultra-flexible lipid vesicles, the elastic liposomes
bearing meloxicam-β-cyclodextrin
complex were prepared for its topical administration with
the aim of simultaneously exploiting the favorable properties
of both the carriers. The prepared meloxicam-β-cyclodextrin
complex was evaluated using DSC, XRD and FT-IR, which indicates
the formation of inclusion complex in a molar ratio of 1:2
of meloxicam and β-cyclodextrin
(β-CD).
The elastic liposomes were prepared by conventional rotary
evaporation method and characterized for various parameters
such as vesicle shape and surface morphology, size and size
distribution, entrapment efficiency, elasticity, stability
and in-vitro release pattern. Permeability studies
of meloxicam and meloxicam-β-cyclodextrin
complex, as such or incorporated in elastic liposomes performed
both across artificial membranes and rat skin highlighted
a favorable effect of cyclodextrin on drug permeation rate,
due to its solubilizing action. Moreover skin-permeation enhancer
property of elastic liposomes has been evidenced. Skin permeation
potential of the developed formulation was assessed using
confocal laser scanning microscopy (CLSM), which revealed
an enhanced permeation of the formulation to the deeper layers
of the skin (up to 160 μm)
following channel like pathways. Skin permeation profile of
elastic liposomal formulation bearing meloxicam-β-cyclodextrin
complex was observed and the investigations revealed an enhanced
transdermal flux (12.48±0.9 μg/cm2
/ h) and decreased lag time (0.7 h) for meloxicam.
The obtained flux was nearly 1.4 and 9.1 times higher than
elastic liposomal formulation bearing meloxicam and plain
drug solution, respectively (P<0.005). The results indicate
that the elastic liposomes may be promising vehicles for the
transdermal delivery of meloxicam.
[Back to top]
Methotrexate Bearing Calcium Pectinate Microspheres:
A Platform to Achieve Colon-Specific Drug Release
M. Chaurasia, M.K. Chourasia, Nitin. K.
Jain, A. Jain, V. Soni, Y. Gupta
and S.K. Jain
In the present work calcium pectinate (Ca-pectinate)
microspheres were prepared to deliver methotrexate in the
environment of colon. Calcium pectinate microspheres were
prepared by modified emulsification method using calcium chloride
as cross linker. All the formulations were evaluated for various
physicochemical parameters. Particle size of the microspheres
was determined using laser diffraction particle size analyzer.
Encapsulation efficiency was determined by digesting with
enzyme pectinase for 24 hours and swellability by equilibrium
swelling in simulated gastrointestinal fluid. The in vitro
drug release studies were performed in simulated gastric fluid
for 2 hours and simulated intestinal fluid for 3 hours. In
vitro release rate studies were also carried out in simulated
colonic fluid in presence of rat caecal contents. Moreover,
release rate studies were also carried out after enzyme induction
by treating the rats with 1 ml of 1% w/v aqueous dispersion
of pectin for 7 days. Mean particle size of the microspheres
was found to be in the range of 20.82±1.34 to 32.26±1.59
µm whereas the entrapment efficiency varied from 52.28±0.32
to 74.01±3.32%. The in vitro drug release
studies in simulated gastric fluid and simulated intestinal
fluid showed that only 8.15±0.49% drug was released
in 5 hours whereas most of the loaded drug was released in
simulated colonic fluid containing pectinase. In vitro
release rate study showed release of 69.94±3.46% of
drug in presence of 3% rat caecal contents, which was further
increased to 94.43±4.48% when enzyme induction was
carried out for 7 days. Thus, it is concluded that calcium
pectinate microspheres can be used to effectively localize
the release of drug in the physiological environment of colon.
[Back to top]
Floating Microspheres as Drug Delivery System: Newer
Approaches
Sunil K. Jain, Govind P. Agrawal and Narendra
K. Jain
A controlled drug delivery system with prolonged residence
time in the stomach can be of great practical importance for
drugs with an absorption window in the upper small intestine.
The main limitations are attributed to the inter- and intra-subject
variability of gastro-intestinal (GI) transit time and the
non-uniformity of drug absorption throughout the alimentary
canal. Floating drug delivery systems (FDDSs) are expected
to remain buoyant in a lasting way upon the gastric contents
and consequently to enhance the bioavailability of drugs.
The various buoyant preparations include hollow microspheres,
granules, powders, tablets, capsules, pills and laminated
films. Floating microspheres are specially gaining attention
due to their wide applicability in the targeting of drugs
to stomach. These floating microspheres have the advantage
that they remain buoyant and distributed uniformly over the
gastric fluid to avoid the vagaries of gastric emptying and
release the drug for prolonged period of time. A major drawback
of low-density floating drug delivery systems is that their
performance is strongly dependent upon the gastric emptying
process of stomach. Multiparticulate low-density particles
can successfully prolong the gastric retention time of drugs.
This article is a review of two important approaches utilized
to prepare and improve the performance of floating microspheres.
[Back to top]
Stem Cell Implantation for Myocardial Disorders
Kenichi Yamahara and Noritoshi
Nagaya
Cell therapy is currently attracting growing interest
as a potential new means of improving the prognosis of patients
with heart failure. For practical reasons, autologous skeletal
myoblasts have been the first to be tested in clinical trials,
but recently cardiovascular researchers has explored many
other cell types, including bone marrow cells, endothelial
progenitor cells, mesenchymal stem cells, embryonic stem cells,
and resident cardiac stem cells. While recent experimental
studies and early-phase clinical trials seem to support the
concept that cell therapy may enhance cardiac repair, many
challenges remain before achieving this goal. Further studies
should focus on finding the optimal donor cells for transplantation,
the mechanism by which engrafted cells improve cardiac function,
controlling the survival and proliferation of transplanted
cells, and the development of more efficient cell delivery
techniques.
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