Bio-organic Nanoparticles: Breaking the Barrier in Nanoparticle-mediated Pulmonary Drug delivery-Juniper publishers
JUNIPER PUBLISHERS-OPEN ACCESS INTERNATIONAL JOURNAL OF PULMONARY & RESPIRATORY SCIENCES
Introduction
Nanoparticles (NPs) are emerging as potentially
effective targeted drug delivery systems because of their non-invasive
approach and lesser bioavailability in the systemic circulation. This
specific approach also reduces the potential adverse effects in compared
to the drugs administered through oral or invasive routes. NPs also
provide an efficient way to selectively deliver ultra-small drugs
molecules to the lungs for a better absorption. However, delivering
nanoparticles-mediated drugs to the lungs is quite challenging. In lung
diseases such as asthma, chronic obstructive pulmonary disease (COPD) or
fibrosis, the airways produce excessive amount of mucus as a result of
goblet cell hyperplasia and sustained level of severe inflammatory
reactions [1].
Controlling inflammation in these persistent
inflammatory conditions is the primary target of a successful treatment,
however in spite of recent advancement of nanoparticles-based drug
delivery systems in various disease conditions; very few have been
tested in respiratory illnesses [2-4]. Moreover, the potential toxicity
of inorganic nanoparticles is a major concern, therefore it is important
to formulate a career molecule which is biodegradable and does not have
any potential toxic effects. Solid lipid nanoparticles (SLNs) are being
tested as one of the most effective ways of pulmonary drug delivery.
SLNs are aqueous nanoscale molecules prepared from phospholipid
compounds mainly triglycerides and phospholipids with a potential
physiological acceptability [5-7]. Along with SLNs, lipophilic drug
delivery through biodegradable polymeric nanoparticles is being tested
for their solubility in lipid matrices which could provide an effective
therapeutic advantage. Because of thephysiological components used in
the formulations of the SLNs, they provide a better and safe delivery of
drugs to the lungs and since its first application long back in the
early 90s, SLNs have been tested as a carrier of a large number of drug
molecules such as amikacin, an aminoglycoside antibiotic and have been
proved to deliver the drugs effectively to the lungs in the treatment of
lung infections [8].
The challenge of pulmonary drug delivery might be
achieved by nanoparticulated formulations such as biodegradable
polymeric nanoparticles, nanoformulations of drug, and dendrimers. Their
relatively higher adsorption rate, biodegradable and almost nontoxic
nature provide significant advantages to them as therapeutic choice in
compared with other types of materials such as metallic or carbon
nanomaterials. Recently, a number of polymeric materials are being
investigated for pulmonary drug delivery because of their several
advantages such as modified surface properties, high encapsulation of
the drug and protection of the drug from degradation, prolonged drug
delivery and a long shelf life. The most commonly used polymers which
are gaining attention as therapeutics are poly(lactic acid) (PLA),
poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL),
alginate, chitosan and gelatin base.
Recently, a combination of polyethylene glycol
(PEG5000) and polymer poly(ethylene oxide)-block-distearoyl
phosphatidylethanolamine (DSPE) was used to prepare a paclitaxel-loaded
polymeric micelle and an in vivo models using intratracheal instillation
demonstrated a better drug absorption in comparison with the
intravenous route of administration [9]. Liposomes have also been a
preferable mode of pulmonary drugdelivery because of its primary
component, phospholipid. One
key advantage of liposomes is that these molecules can be used
for drugs which require a sustained release that means a precise
and controlled release of the drug molecules over a long period
of time for a maximum effect. The first liposome-coupled drug
was produced 20 years back. Alveofact®, the first generation
product of liposome-drug combination was used to treat acute
respiratory distress syndrome (ARDS) in infants by pulmonary
instillation [10].
Although liposomes have always been a preferred choice for
pulmonary drug delivery, maintaining the physical properties
of the liposomes in inhalation devices is a great challenge and
therefore it is important to stabilize the product. Nanoformulation
of drug has also achieved a great importance for pulmonary drug
delivery. It is basically a sole entity, which means that the drug
itself is converted into nano-size particles and does not require
any carrier molecule. Some of these drugs such as dry powder
sodium alendronate can be easily delivered through inhalation
devices. Dendrimers are getting attention as in these days.
These are nano-size synthetic macromolecules with a highly
branched structure and globular shape. Dendrimers contain a
large number of terminal groups, which allows these molecules
to bind with several drugs at the same time and can deliver them
with accuracy and precision.
There are several dendrimer-based formulations
available, such as anticancer drug fluorouracil attached to the
dendrimers with cyclic core and antitumor drugs adriamycin
and methotrexate with dendrimers having poly(ethylene
glycol) grafts. Precision and targeted drug delivery is rapidly
gaining importance now a days and considering the mechanical
improvement of formulation and delivery devices, nanoparticles
and nanoparticles-mediated drug delivery are at the peak.
However, since the characteristics of the engineered nanocarriers
or nano formulations are complex and may change in certainsolutions or devices, t is important to focus on the development
of appropriate devices to deliver the drugs effectively. Preclinical
and animal studies are extremely important at this stage to
investigate the efficacy and safety of these formulations before
bringing them as regular treatment modality.
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