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| Pharmaceutical Drug Delivery |
Drug delivery refers to the methods and processes used to administer drugs for
safe and effective therapeutic purposes. The goal of any drug delivery system
is to control the rate, location and duration of drug release in the body.
Effective drug delivery ensures drugs act at intended sites in the body at
therapeutic concentrations for sufficient periods of time to exert desired
therapeutic effects. Over the past few decades, advanced drug delivery systems
have emerged as one of the most promising areas of pharmaceutical research and
development with tremendous potential to revolutionize medicine.
Targeted Drug Delivery
One of the major challenges of traditional drug therapy has been the lack of
selectivity—medications circulating throughout the entire body affecting both
diseased and healthy cells. This often results in dose-limiting side effects by
acting on off-target organs and tissues. Targeted drug delivery aims to
overcome these limitations by directing pharmaceutical compounds specifically
to diseased sites while avoiding unwanted interactions with healthy cells and
tissues. Various targeting approaches have been developed including passive
targeting that exploits unique pathophysiological properties at disease sites and
active targeting employing targeting ligands/moieties that bind selectively to
receptors overexpressed on diseased cells.
Nanoparticle-based Pharmaceutical
Drug Delivery such as liposomes, polymeric nanoparticles, metallic
nanoparticles etc. have emerged as promising carriers for targeted delivery of
chemotherapeutics, proteins, nucleic acids and other biologics. Surface
functionalization of nanoparticles with antibodies, peptides, aptamers,
hyaluronic acid and other homing devices facilitates selective interactions
with disease markers resulting in accumulation of drugs at target sites. This
targeted approach significantly enhances therapeutic efficacy and safety by
reducing systemic exposure. Examples include FDA-approved Doxil—a liposomal
formulation of doxorubicin for ovarian cancer and metastatic breast cancer
treatment. Ongoing research is being conducted to develop new modalities like
cellular tumor-penetrating nanoparticles, disease-activated prodrugs etc. for
disease-specific targeting.
Controlled Release Formulations
One of the core aspects of modern drug delivery involves formulation of
pharmaceuticals as controlled or sustained release drug delivery systems to
optimize pharmacokinetic and pharmacodynamic profiles. These systems release
drugs at predetermined rates and for prolonged periods of time achieving
constant therapeutic levels while avoiding peak-valley fluctuations associated
with immediate/conventional release products. Controlled release formulations
offer significant benefits like reduced dosing frequency, improved patient
compliance and constant drug levels over extended periods for chronic
therapies.
Major controlled release technologies include matrix diffusion systems,
reservoir devices, osmotic drug delivery, transdermal patches etc. Matrix
systems like extended release tablets, capsules incorporate drugs homogenously
within inert hydrophilic/lipophilic matrices that govern release kinetics.
Reservoir devices consist of an impermeable capsule encasing drugs surrounded
by a rate-controlling membrane. They release drugs continuously through
miniature openings in the membrane at optimized rates. Osmotic pumps utilize
osmotic pressure difference across a semi-permeable membrane for controlled
drug expulsion. Transdermal patches adhere to the skin surface releasing drugs
at predetermined rates through the skin for systemic absorption. Many such
long-acting injectable formulations and implants are also being developed.
Advances in Controlled Gene Therapy
Gene therapy has transformative potential to treat diseases at their genetic
roots by correcting abnormal genes/replacing missing ones. However,
uncontrolled and short-lived expression has hampered its progress. Controlled
gene delivery employing advanced vectors and regulatory elements now enables
transient and sustained expression patterns mimicking endogenous genes.
Integrating gene expression cassettes within viral/non-viral vehicles governed
by cell/tissue-specific promoters facilitates targeted expression in affected
cells/tissues. Combining biomaterials with gene vectors forms controlled
environment for optimal expression kinetics.
Inducible gene expression systems like Tet-On/Tet-Off using tetracycline
response elements provide temporal and dose-dependent control over transgene
expression duration through small molecule inducers. Analogous approaches
utilize heat shock protein promoters, aptamers etc. Synthetic biology tools
design tunable gene networks with built-in safety features giving tightly
regulated dynamic expression profiles. These innovations address previous
limitations and bring us closer to clinically translatable gene therapies for
various conditions like cancer, ocular diseases, metabolic disorders.
Cutting-edge technologies like programmable CRISPR/Cas systems also enable
regulated gene editing for next-gen therapeutics.
Advanced Delivery of Biologics
Biologics have revolutionized treatment of various diseases but suffer from
poor oral bioavailability necessitating parenteral administration involving
hospitals, specialized staff and high costs. Advanced delivery strategies aim
to develop alternative non-parenteral routes for biologics administration. Oral
delivery employs absorption enhancers, enzymatic protectants, mucoadhesive
systems etc. to facilitate their transport across GI barriers. Pulmonary route
utilizes inhalable powders/aerosols harnessing lung’s enormous surface area for
absorption. Transdermal patches, microneedle arrays, iontophoresis and
sonophoresis enable efficient skin transport avoiding pre-systemic clearance in
the liver. Buccal, sublingual routes utilize oral mucosal layers as potential
non-invasive entry sites. Novel injectable platforms like dissolving
microneedle arrays, hydrogels enable gradual release of biologics avoiding
’bolus effect’. These innovative strategies hold promise to transform biologics
therapy through convenient non-invasive administration paving way for enhanced compliance
and accessibility.
The past few decades have witnessed remarkable progress in the field of drug
delivery ushering in a new era of personalized therapies. Advancements in areas
of targeted delivery, controlled release formulations, gene and biologics
delivery hold immense potential to revolutionize pharmaceutical treatments
through safer and enhanced therapeutics. Current research is focused on
developing novel platforms integrating multifaceted strategies like
stimuli-responsiveness, 3D printing, microfabrication for precision medicine.
As technologies continue advancing at exponential rates, future drug delivery
systems promise to deliver right medications to right patients in right amounts
for right durations - a major leap towards resolving many unmet medical needs.
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Drug Delivery