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Current Drug Delivery
ISSN: 1567-2018
Current Drug Delivery
Volume 3, Number 2, April 2006
Contents
Biphasic Lipid Vesicles as a Subcutaneous Delivery System
for Protein Antigens and CpG Oligonucleotides Pp. 129-135
Valeria L. Alcón, Maria E. Baca-Estrada, Andrew
Potter, Lorne A. Babiuk, Praveen Kumar and Marianna Foldvari
[Abstract]
Vaccine Delivery - Current Trends and Future
Pp. 137-146
Neelam Azad and Yon Rojanasakula
[Abstract]
Delivery Strategies for siRNA-mediated Gene
Silencing Pp. 147-155
Ian R. Gilmore, Stephen P. Fox, Andrew J. Hollins and
Saghir Akhtar
[Abstract]
Sustained and Targeted Delivery of an Anti-HIV
Agent Using Elastic Liposomal Formulation: Mechanism of Action
Pp. 157-166
Subheet Jain, A.K. Tiwary and N.K. Jain
[Abstract]
Microemulsions: A Potential Drug Delivery
System Pp. 167-180
P.K. Ghosh and R.S.R. Murthy
[Abstract]
ADME Related Profiling in 96 and 384 Well
Plate Format – A Novel and Robust HT-Assay for the Determination
of Lipophilicity and Serum Albumin Binding Pp. 181-192
Thorsten Hartmann, Johannes Schmitt, Cornelia Röhring,
Daniel Nimptsch, Joachim Nöller and Christoph Mohr
[Abstract]
Controlled Porosity Osmotic Pump for the
Delivery of Flurbiprofen Pp. 193-198
C.S. Chauhan and P.K. Choudhury
[Abstract]
Role of ABC Transporters in Veterinary
Drug Research and Parasite Resistance Pp. 199-206
Ana I. Alvarez, Gracia Merino, Antonio J. Molina, Mivis
M. Pulido, Quintin A. McKellar and Julio G. Prieto
[Abstract]
Review of Ocular Drug Delivery
Pp. 207-217
Yasmin Sultana, R. Jain, M. Aqil and Asgar Ali
[Abstract]
A Review of Nanocarrier-Based CNS Delivery Systems
Pp. 219-232
Sandip B. Tiwari and Mansoor M. Amiji
[Abstract]
Abstracts
[Back
to top]
Biphasic Lipid Vesicles as a Subcutaneous Delivery System
for Protein Antigens and CpG Oligonucleotides
Valeria L. Alcón, Maria E. Baca-Estrada, Andrew
Potter, Lorne A. Babiuk, Praveen Kumar and Marianna Foldvari
One of the major drawbacks to the development of novel vaccines
has been the lack of safe yet effective adjuvants. Biphasic
lipid vesicles are formulations suitable for the delivery
of proteins, peptides and oligo/polynucleotides. They constitute
a new class of delivery system into which antigens and adjuvants
can be incorporated. The purpose of these studies was to investigate
the ability of biphasic lipid vesicles (Vaccine-Targeting
Adjuvants - VTA) to induce immune responses to bacterial antigens
and to enhance the adjuvant activity of CpG ODNs. Immunization
of mice with bacterial antigen and CpG ODNs in saline was
not as effective at inducing immune responses as formulation
in VTA vesicles. Results showed that formulation of CpG ODN
in VTA significantly enhanced its adjuvanticity.
[Back to top]
Vaccine Delivery - Current Trends and Future
Neelam Azad and Yon Rojanasakula
Since its discovery in 1796 by Edward Jenner, vaccines have
been an integral aspect of therapeutics, combating a number
of infectious diseases with remarkable success. In recent
years, due to rapid advances in proteomics, genomics, biotechnology
and immunology and the plethora of knowledge amassed in related
fields, it is fair to expect vaccine development to progress
at an exponential pace. However, as we march on into the 21st
century, we are still struggling in our efforts to eradicate
fatal diseases such as AIDS, malaria and hepatitis C due,
in part, to the absence of effective vaccines against these
diseases. Vaccine development faces major challenges both
technologically and economically. Newer vaccines that are
stable, economical, require fewer doses and can be administered
using needle free systems are a worldwide priority. An ideal
theoretical vaccine may not be cogent unless formulated and
delivered aptly. Delivery of vaccines via oral, intranasal,
transcutaneous and intradermal routes will decrease the risk
of needle-borne diseases and may eliminate the need for trained
personnel and sterile equipment. Crucial to the success of
a vaccine is the delivery strategy that is to be employed.
Currently, various techniques involving DNA vaccines, adjuvants,
microparticles and transgenic plants are being developed and
evaluated. Although, no major breakthrough is in prospect,
these systems have potential and will take immunization to
a new technological level. This review will focus on the current
development of some novel vaccine delivery systems and will
explore the non-parenteral routes of vaccine administration.
[Back to top]
Delivery Strategies for siRNA-mediated Gene Silencing
Ian R. Gilmore, Stephen P. Fox, Andrew J. Hollins and
Saghir Akhtar
RNA interference (RNAi) represents a promising new gene silencing
technology for functional genomics and a potential therapeutic
strategy for a variety of genetic diseases. RNAi involves
the targeted post-transcriptional degradation of messenger
RNA thereby inhibiting the synthesis of the desired protein.
This effectively leads to silencing of gene expression. The
effectors of this process are short interfering RNA (siRNA)
duplexes (~21-23nt) that are key intermediaries in the specific
degradation of target mRNA following incorporation into the
RNA-induced silencing complex (RISC) in the cytosol. However,
due to the large molecular weight and negative charge of siRNA
duplexes the effective cellular up-take and intracellular
delivery appear to represent a major challenge for the widespread
use of RNAi in vivo. This review summarises some
of the main delivery strategies that have been attempted for
the transfection of siRNA to cells in vitro and
in vivo.
[Back to top]
Sustained and Targeted Delivery of an Anti-HIV Agent
Using Elastic Liposomal Formulation: Mechanism of Action
Subheet Jain, A.K. Tiwary and N.K. Jain
The present study is aimed at evaluating
the transdermal route as an alternative to the oral route
for improving the systemic bioavailability and sustaining
the constant therapeutic plasma level of Zidovudine (AZT).
Elastic liposomal formulations of AZT were prepared and characterized.
The effect of different formulation variables on transdermal
delivery of AZT from elastic liposomes was studied. To investigate
the mechanism of skin permeation of elastic liposomes, Transmission
Electron Microscopic (TEM) study was carried out. The optimized
elastic liposomal formulation showed transdermal flux of 98.8
± 5.8
μg/cm2/hr
across rat skin as compared to 5.72 ±
0.3 μg/cm2/hr
for free drug. Vesicle-skin interaction study showed that
elastic vesicles influenced the ultra structure of stratum
corneum. Distinct regions with lamellar stacks derived from
vesicles were observed in intercellular spaces of the stratum
corneum. These stacks disrupted the organization of skin bilayers
leading to increased skin permeability, whereas no changes
were observed in the underlying viable epidermis and dermis.
Improved pharmacokinetic profile was observed when AZT was
entrapped in elastic liposomes. The AUC0-24th for
elastic liposomal formulation was found to be (12.63±1.2
μg
h/mL), nearly twelve fold higher than the control (0.83±0.2
μg
h/mL). Furthermore, the administration of elastic liposome
encapsulated AZT resulted in substantially higher accumulation
of AZT in target RES organs that play a key role in the pathogenesis
of AIDS by providing long-term reservoir for the virus. The
results of the present study demonstrated that elastic liposomes
increased the transdermal flux, prolonged the release, improved
the site specificity of AZT and represented an attractive
strategy for sustained and targeted delivery of AZT.
[Back to top]
Microemulsions: A Potential Drug Delivery System
P.K. Ghosh and R.S.R. Murthy
Microemulsions are clear, transparent, thermodynamically
stable dispersions of oil and water, stabilised by an interfacial
film of surfactant frequently in combination with a co-surfactant.
Recently, there has been a considerable interest for the microemulsion
formulation, for the delivery of hydrophilic as well as lipophilic
drug as drug carriers because of its improved drug solubilisation
capacity, long shelf life, easy of preparation and improvement
of bioavailability. In this present review, we discuss about
the various advantages of microemulsion in pharmaceuticals,
along with its composition variables, physicochemical characterisation
etc. The potential use of microemulsion for therapeutic application
is also discussed.
[Back to top]
ADME Related Profiling in 96 and 384 Well Plate Format
– A Novel and Robust HT-Assay for the Determination
of Lipophilicity and Serum Albumin Binding
Thorsten Hartmann, Johannes Schmitt, Cornelia Röhring,
Daniel Nimptsch, Joachim Nöller and Christoph Mohr
The failure of about half of the drug candidates
is associated with poor pharmacokinetic properties leading
to a huge loss of time and money [1]. Early profiling of drug
like properties provides important information in order to
screen out insoluble, poorly absorbed and toxic compounds.
Today, large compound libraries have to be screened, and of
course the total number of compounds will rise over the next
years leading to a growing demand for fully automated assays.
A balance between quality, speed, throughput, cost and information
content can be accomplished by the careful selection of assays
and experimental conditions. Here we describe a novel 384
well format assay for two important ADME related descriptors
(lipophilicity and serum protein binding) as input parameters
for a precise prediction of fraction absorbed, blood/organ
distribution coefficients and permeability, in order to maximize
the information about a compound at an early stage of discovery.
[Back to top]
Controlled Porosity Osmotic Pump for the Delivery
of Flurbiprofen
C.S. Chauhan and P.K. Choudhury
Controlled porosity osmotic pump contains
water-soluble additives in the coating membrane, which in
contact with aqueous environment dissolves and results in
formation of micro porous membrane. The resulting membrane
is substantially permeable to both water and dissolved drug.
The drug release from this type of system is independent of
pH and follows zero order kinetics.
In the present investigation, effort has been made to study
release mechanism of drug having low water solubility by means
of controlled porosity osmotic pump. The capsule membrane
was prepared by phase inversion technique. The phase inversion
was carried by dipping the stainless steel mould in a 15%
solution of cellulose acetate containing varying amounts of
pore-forming agent, glycerol (50% to 70% w/w), followed by
quenching in an aqueous solution (10% w/v glycerol), which
resulted in the formation of the asymmetric membrane. The
delivery orifices so formed were confirmed by release of an
encapsulated dye from the capsule and scanning electron microscope
(SEM).
The drug selected for this study, Flurbiprofen, has low water
solubility and hence is unable to create osmotic pressure
to cause drug release. To enhance the solubility and its osmotic
pressure, this study was conducted with a solubility enhancer
sodium lauryl sulfate (SLS). The quantity of SLS was predetermined
by conducting a solubility study of flurbiprofen with SLS.
Release rate studies reveled that less than 10% of drug was
released from the system without SLS, while about 75% release
was observed from systems containing SLS. The release rate
increased as the concentration of pore forming agent increased.
[Back to top]
Role of ABC Transporters in Veterinary Drug Research
and Parasite Resistance
Ana I. Alvarez, Gracia Merino, Antonio J. Molina, Mivis
M. Pulido, Quintin A. McKellar and Julio G. Prieto
A considerable body of research has been
carried out in order to throw light on the pharmacological
and toxicological impact of ATP-binding cassette (ABC) drug
efflux transporters such as P-glycoprotein and Breast Cancer
Resistance Protein (BCRP/ABCG2/MXR). Most studies focus on
their role in rendering cancer cells resistant to anticancer
drugs. Drug transporters are expressed in many tissues and
they are strongly involved in the oral bioavailability, and
the hepatobiliary, direct intestinal and renal excretion of
many drugs. In veterinary therapy, some anti parasitic drugs
and/or their metabolites, such as ivermectin, moxidectin,
albendazole sulfoxide, which are widely used, have been shown
to be actively transported by efflux pumps. This interaction
plays an important role in drug disposition since its inhibition
has been shown to increase the drug bioavailability in some
domestic species. Moreover, some authors have reported that
parasite resistance to anthelmintic drugs may be mediated
by parasite P-glycoprotein efflux. In addition, the importance
of milk residues for human nutrition has aroused increasing
concern about the inadvertent transfer of drugs and other
substances into mammary milk of domestic animals, potentially
posing a health risk to consumers. Recently, the important
role of BCRP in the secretion of its substrates in milk has
been demonstrated.
[Back to top]
Review of Ocular Drug Delivery
Yasmin Sultana, R. Jain, M. Aqil and Asgar Ali
Successful treatment of eye diseases requires
effective concentration of drug at the eye for sufficient
period of time. Conventional ocular drug delivery including
eye drops, systemic administration, ophthalmic ointments,
is no longer sufficient to combat ocular diseases. This article
reviews the constraints with conventional ocular therapy,
and explores various novel approaches, to improve the ocular
bioavailability of drugs to the anterior chamber of the eye.
[Back to top]
A Review of Nanocarrier-Based CNS Delivery Systems
Sandip B. Tiwari and Mansoor M. Amiji
Drug delivery to the central nervous system
(CNS) is one of the most challenging fields of research and
development for pharmaceutical and biotechnology products.
A number of hydrophilic therapeutic agents, such as antibiotics,
anticancer agents, or newly developed neuropeptides do not
cross the blood brain barrier (BBB) after systemic administration.
The BBB is formed by the tight junctions at the brain capillary
endothelial cells, which strictly control drug transfer from
blood to brain. Drug modification, osmotic opening of cerebral
capillary endothelium, and alternative routes for administration
(e.g., intracerebral delivery) have been successfully used
to enhance drug transport to the CNS. The use of nanocarriers,
such as liposomes and solid polymeric or lipid nanoparticles
may be advantageous over the current strategies. These nanocarriers
can not only mask the BBB limiting characteristics of the
therapeutic drug molecule, but may also protect the drug from
chemical/enzymatic degradation, and additionally provide the
opportunity for sustained release characteristics. Reduction
of toxicity to peripheral organs can also be achieved with
these nanocarriers. This review article discusses the various
barriers for drug delivery to the CNS and reviews the current
state of nanocarriers for enhancing drug transport into the
CNS.
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