Siraj Sir Artical Ijprd
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ABSTRACT
Pulmonary drug delivery system is a needle free technique. The origin of inhaled therapies seen in
back 4000 years ago to India, where people smoked the leaves of the Atropa belladonna plant to
suppress cough. In the 19th and early 20th centuries, asthmatics smoked asthma cigarettes that
contained stramonium powder mixed with tobacco to treat the symptoms of their disease. Now a day’s
pulmonary drug delivery remains the preferred route for administration of various drugs. It is an
important research area which impacts the treatment of illnesses including asthma, chronic obstructive
pulmonary disease and various diseases. Drug is delivered directly to the conducting zone of the lungs.
In this article, we summarize recent advances in applications of pulmonary drug delivery system.
previously pulmonary drug delivery is used for management of Asthma and COPD only but due
advancement in application nowadays Pulmonary drug delivery is useful to treat Diabetes, angina
pectoris, cancer , bone disorders ,migraine,tuberculosis,acute lung injury and others. .
Key Words: Asthma, pulmonary route, application, bone disorders, inhalation therapy.
The products fall into two main groups the dry Measles infects 30 to 40 million children
powder formulations and solution, which are in underdeveloped nations. Recently inhaled
delivered through different patented inhaler measles vaccine given by nebulizer. As far
systems. E.g. Novel pMDI formulations for back as the 1960s, influenza experts tested
pulmonary delivery of proteins.15, 16,17,18.19,20. aerosol flu vaccines.
(Refer Table No. 01) 8) In emphysema
Emphysema is most popular respiratory
5) In migraine
disorder due to deficiency of Alpha 1 antitrypsin
Ergotamine is drug of choice for migraine. Many uncontrolled neutrophil elastase deficiency
years ago, ergotamine via metered dose inhaler formed which leads to lung destruction and the
was used successfully to treat migraine formation of emphysema. Nowadays
headache.13 recombinant AAT (rAAT) given intravenously
6) Angina pectoris (IV) is very well accepted treatment. Early
evaluation of aerosolized AAT documented
Angina pectoris is not a disease itself it is adequate alveolar fluid AAT and penetration
symptoms of myocardial ischemia it is arises as into the lung interstitum. Neutrophil elastics’
a result of imbalance between oxygen supply inhibitor, secretory leukocyte protease inhibitor,
and demand of myocardium.Nitroglycerine. is has also been considered for protection against
drug of choice for angina pectoris has been elastase in CF and patients with AAT
given generally by sublingual route .It is well deficiency.
known as is a known coronary vasodilator, the
9) Recent use of pulmonary drug delivery in
rapid relief of angina is probably caused by a
transplantation
reduced demand on the heart and the
consequent reduced cardiac work. An aerosol Inhalation route play a role very important role
form has been tested in Europe and has in transplantation. Legion is problems of
been found comparable to sublingual transplanted organs and lung transplantation is
nitroglycerine. In particular, its efficacy has been one of the most difficult transplants to maintain.
found better than nitroglycerine tablets in During lung transplantation, pulmonary vascular
patients with dry mouth. Isosorbide aerosol has pressure and an intrapulmonary shunt have
also been reported useful in hypertensive crisis. been shown to respond to inhaled nitric oxide
In United States inhalation therapy for angina and inhaled aerosolized prostacyclin
pectoris is very well accepted.13 .prostacyclin which is given by pulmonary route
7) Role of pulmonary delivery in vaccination has also been described as an alternative to
21 nitric oxide in the management of reperfusion
injury after lung transplantation. Acute and
While there was moderate interest in chronic rejections are major problems
aerosol vaccination 15–20 years ago, progress compromising transplant and patient survival.
toward application has been modest Aerosolized cyclosporine a is useful for
seen.Nearly 100 vaccines are approved in the reducing the risk of acute rejection. 13
U. S. About half of these prevent respiratory
infections, yet all are currently injected. As
compare to injectable they remove needle fears, 10) In Pulmonary arterial hypertension22
especially in children, but they could also
This is new use of pulmonary route in
generate more potent local immune responses
2004, the FDA approved Ventavis (iloprost), an
than when they are injected into muscles.
inhaled treatment for pulmonary arterial maintenance of expression over time, and
hypertension, made by CoTherix (South San efficacy of expression.
Francisco, CA, U. S. A.). In pulmonary arterial 14) Application of pulmonary drug delivery
hypertension, severe restriction of blood vessels in cancer chemotherapy
results in early death.
11) In acute lung injury13 Cancer is one of major disease which
takes death of people. Lung cancer is the
Drug given by pulmonary route plays very
leading cause of cancer deaths globally, and
important role in acute lung injury. Major inhaled chemotherapy seems a logical
complication of acute lung injury is Hypoxemia approach to treat lung cancer.
and it is often difficult to manage. Mediators
such as nitric oxide and prostacyclin can A multicenter Phase I clinical trial is
improve oxygenation by increasing blood flow evaluating doxorubicin HCI inhalation solution in
through ventilated areas. Prostaglandin E1 lung cancer patients. As many as 400 000 lung
(PGE1) by continuous aerosol via a ventilator cancer patients could benefit from inhaled
has also been shown to improve oxygenation. chemotherapy; a study is going on aerosolized
paclitaxel solution to mice with lung tumors. The
12) Application of pulmonary drug delivery
treatment significantly reduced lung tumors and
as a surfactant aerosol
prolonged survival. Aerosol delivery of the anti-
In respiratory distress of premature infants and cancer agent’s difluoro methylornithine and 5-
neonatal surfactant plays important role. In fluorouracil reduced lung tumors in mice 50 %
adults loss of surfactant is probably a and 60 %, respectively. Interleukin-2 stimulates
contributing factor in pathogenesis of acute immune function in cancer patients, but
respiratory distress syndrome. A recent study injections cause fever, malaise, and local
showed no difference in outcome for swelling. 24
spontaneously breathing newborns who inhaled
either surfactant or placebo via a CPAP mask. 15) Delivery of pentamidine by pulmonary
There continues to be great appeal for the use route25
of surfactant in adults because of the apparent protozoan Pneumocystis carinii(PCP) is
success in neonates, but its use should not major cause of Pneumonia in Patients with
become practice until well controlled trials acquired immunodeficiency syndrome . Aerosol
document clinically meaningful efficacy. pentamidine is not only useful in treating mild
13) Gene therapy via pulmonary route23 PCP and, but also for prophylaxis against PCP.
This is new research in application of Pentamidine aerosol is delivered to the alveolar
space, where the P. carinii organisms are
pulmonary drug delivery .Main aim Gene
found. The deposition fraction of pentamidine is
therapy given by pulmonary route is treatment
relatively low, around 2–3% of total dose in the
of cystic fibrosis. Cationic-lipid-mediated CFTR
nebulizer but as a fraction of total lung capacity,
gene transfer can significantly influence the
it is greater in children, and so there is need to
underlying chloride defect in the lungs of
reduce the dose in children.
patients with CFC. There are many problems to
16) Delivery of Amphotericin by pulmonary
be overcome before clinical applications are
route26
practical. Some of these are safety, successful
transfer of sufficient genetic material to Now days Amphotericin aerosol has been
appropriate tissue, adequate gene expression, successfully used to treat various infections.
Such use should not become clinical practice cessation. Nicotine for inhalation and for nasal
without good randomized controlled trials. delivery is available, and studies indicate some
improvement in the success of cessation efforts
Ribavirin aerosol has also been used for
beyond placebo. Inhaled nicotine substitution
treatment or prophylaxis following bone marrow
for cigarettes has much potential because it
transplantation but controlled trials are needed
most mimics delivery by smoking, giving a rapid
to better clarify efficacy.
rise in blood nicotine level.
17) Delivery of Gentamycin by pulmonary 20) Inhaled drug delivery for tuberculosis
route therapy28
Tuberculosis is most infectious diseases
For chronic Pseudomonas aeruginosa
because One third of the world population is
(PA) infections in CF gentamycin given by
infected with tuberculosis and new infections
pulmonary route plyas important role.It was
occur at a rate of one per second. The urgency
observed daily inhalations of gentamicin delays
to treat TB may be addressed with approaches
the acquisition of chronic PA infections and
consisting of newer drugs and delivery systems
decreases disease progression in children with
The recent increase in the emergence of drug-
zanamivir, made by GSK, was the first inhaled
resistant strains of Mycobacterium tuberculosis
anti-viral medication approved by the FDA in
1999. For treatment of flue dose of dry powder and the dearth of anti-TB drugs is threatening
inhalers is twice daily for 5 days. 27 the future containment of TB. Administering
drugs by the pulmonary route to the lungs
allows higher drug concentrations in the vicinity
8) Diagnostic application pulmonary drug of these lesions. Supplementing conventional
delivery 27 therapy with inhaled antiTB therapy may allow
therapeutic concentrations of drug to penetrate
Pulmonary drug delivery is not only effectively into lung lesions and treat the
useful for therapeutic purpose but also for resident mycobacterium. Drugs Used
diagnosis purpose. Several diagnostic tests Experimentally to Treat TB by the Pulmonary
utilizing specific-size nonradioactive aerosols Route is as rifampicin, ionized and
and also radioactive aerosols with standard pyrazinamide.
nuclear medicine technology are practiced in
respiratory medicine. For example, inhalation of As we know that drug resistance is major
aerosols of methacholine and histamine is hurdle in treatment of tuberculosis if drugs given
widely used to assess nonspecific bronchial by pulmonary route for management of TB
responsiveness in asthma. reduces chances of drug resistance TB.Various
drug delivery systems such as micro particles,
nanoparticles and Liposomes can be delivered
19) Nicotine aerosol for smoking cessation to the periphery of the lungs for instantaneous
As we know that smoking is injurious to health and targeted or controlled release. This may
.It is very difficult to cess such habit. From lead to therapeutically effective drug
ancient times people smokes cigarette and get concentrations in regions of the lungs
addicted with smoking. Primary reason for containing large burdens of bacteria. Aerosol
cigarette smoking is Nicotine addiction, and delivery to the lungs as an adjunct to
nicotine replacement is appealing as a means conventional therapy has the potential to
of reducing cigarette use to ultimately achieve decrease the dosing frequency and the duration
of therapy. This may ultimately lead to less delivered by inhalation route of using
severe side effects, improved patient aerosolized insulin encapsulated liposomes.
compliance and reduced emergence of drug Liposomes, as a pulmonary drug
resistant strains of TB. delivery vehicle, have been studied for years
21) Pulmonary delivery of lower molecular and used as a means of delivering
weight Heparin29 phospholipids to the alveolar surface for
treatment of neonatal respiratory distress
Now days , low molecular weight syndrome. More recently, they have been
heparins is better as an alternative to investigated as a vehicle for sustained-release
unfractionated heparin because of improved therapy in the treatment of lung disease, gene
pharmacokinetic profiles and reduced cost of therapy and as a method of delivering
therapy in the treatment of deep vein therapeutic agents to the alveolar surface for
thrombosis and pulmonary embolism . Low the treatment of systemic diseases.
molecular weight heparins are given by Liposomes can be produced from a variety of
subcutaneous and intravenous routes. phospholipids from natural sources, that are
Administration of an anticoagulant drug directly endogenous to the lungs and that carry either
to the pulmonary circulation would be ideal for no charge or net negative or positive
the treatment of pulmonary embolism. A charges.30,31,32. 33
pulmonary formulation of LMWH will allow direct
23) Recent use of pulmonary delivery for
administration of the drug into the lungs, and
bone disorders34
consequently this formulation is likely to reduce
the mortality from an attack of pulmonary Disease such as osteoporosis and
embolism. This pulmonary therapy is non Paget’s disease of bones can be treated by
invasive because it is needle free. pulmonary delivery. The predicted increase in
22) Controlled delivery of drugs to lungs by the number of patients with osteoporosis and
pulmonary route the lack of ideal therapies dictates the need for
better treatments. Clinical evidence from a
Recent application of pulmonary drug
variety of other peptides and proteins indicates
delivery is controlled delivery by lungs. Most
that pulmonary delivery is safe, efficient, well
Drugs in inhalation required to be take 3-4 times
tolerated and preferred by patients so
in day because of its short duration action so
pulmonary route is better option to treat bone
sustained release of drugs in lungs prolong
disorders.
action in lung for that Liposomes, microsphere
Nanoparticles carriers are used Sustained Following are drugs used to treat osteoporosis
release from a therapeutic aerosol can prolong are the naturally occurring peptides calcitonin
the residence of an administered drug in the and parathyroid hormone, which regulate bone
airways or alveolar region, minimize the risk of metabolism. For the peptides to become viable
adverse effects by decreasing its systemic therapies, formulations must be developed that
absorption rate, and increase patient bypass the need for injection. Pulmonary
compliance by reducing dosing frequency. E.g. delivery of calcitonin and parathyroid hormone
ribavirin aerosol, novel sustained released appears likely in the near future.
microspheres for pulmonary drug delivery,
The recent introduction of a nasal
studies showed that plasma glucose level was
formulation of calcitonin points to the feasibility
effectively reduced when liposomal insulin was
of lung delivery. A pulmonary formulation
inhaled through the mouth that delivers
calcitonin or PTH into the deep lung should day’s pulmonary drug delivery remains the
improve the bioavailability and efficacy of the preferred route for administration of various
drugs. drugs. Pulmonary drug delivery is an important
24) Current use of pulmonary delivery of research area which impacts the treatment of
opioids as pain therapeutics35 illnesses including asthma, chronic obstructive
pulmonary disease and various diseases.
For pain management painful inject able
Inhalation gives the most direct access to drug
are given. To avoid pain associated with inject
target. In the treatment of obstructive respiratory
able pain killer Pulmonary opioid delivery is
diseases, pulmonary delivery can minimize
better alternative. Early clinical studies involving
systemic side effects, provide rapid response
inhaled opioids were focused on treatment of
and minimize the required dose since the drug
dyspnoea and not pain management, but they
is delivered directly to the conducting zone of
showed that inhalation of various opioid
compounds is safe, even in severely ill patients. the lungs .It is a needle free several techniques
The advent of specialized and efficient have been developed in the recent past, to
pulmonary drug delivery systems has facilitated improve the Quality of pulmonary drug delivery
the evaluation of inhaled opioids, such as system without affecting their integrity.
morphine and fentanyl, for management of Because of advancement in applications of
pulmonary drug delivery it is useful for multiple
severe pain associated with surgery or
diseases. So pulmonary drug delivery is best
malignant disease. In the past, the few studies
route of administration as compare to other
evaluating pulmonary delivery of opioids for the
routes.
management of severe pain has with limited
success. Earlier attempts at systemic delivery of
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TABLES
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