Pharmaceutical Manufacturing Handbook: Production and

1258 NANOTECHNOLOGY IN PHARMACEUTICAL MANUFACTURING
7.2.3
NANOTECHNOLOGY FOR DRUG DELIVERY
7.2.3.1 Nanocarriers
High - throughput screening technologies in drug discovery present an effi cient way
to fi nd new potential active agents. But in recent years it has become evident that
the development of new drugs alone is not suffi cient to ensure progress in pharmacotherapy.
Poor water solubility of potential active molecules, insuffi cient bioavailability,
fl uctuating plasma levels, and high food dependency are the major and
common problems. Major efforts have been spent on the development of customized
drug carriers to overcome the disappointing in vivo fate of those potential
drugs. For drug carriers the followings are considered: nontoxicity (acute and
chronic), suffi cient drug - loading capacity, possibility of drug targeting, controlled -
release characteristic, chemical and physical storage stability (for both drugs and
carriers), and feasibility of scaling up production with reasonable overall costs.
Nanocarriers have attracted great interest because they are desirable systems to
fulfi ll the requirements mentioned above.
Over the past decade nanocarriers as nanoparticulate pharmaceutical carriers
have been shown to enhance the in vivo effi ciency of many drugs both in pharmaceutical
research and the clinical setting, including liposomes, micelles, nanocapsules,
polymeric nanoparticles and lipid nanoparticles. They perform various
therapeutically or diagnostically important functions. More importantly, many
useful modifi cations have been made, including the increased stability and half - life
of nanocarriers in the circulation, required biodistribution, passive or active targeting
into the required pathological zone, responsiveness to local physiological stimuli
such as pathology - associated changes in local pH and/or temperature, and ability
to serve as imaging/contrast agents for various imaging modalities (gamma scintigraphy,
magnetic resonance imaging, computed tomography, ultrasonography). In
addition, multifunctional pharmaceutical nanocarriers have already made a promising
progress [62] . Some of those pharmaceutical carriers have already found their
way into clinics, while others are still under preclinical investigation. This section
presents two of the most promising nanocarriers, that is, liposomes and nanoparticles,
especially their manufacturing, characteristics, and applications.
Liposomes Liposomes (lipid vesicles) have a relative long history, fi rst discovered
by Banham in 1965 [63] . In the following decades, liposomes rapidly became a useful
drug carrier. During the 1990s, many liposome - based drugs reached the market in
the United States and Europe. The history of liposomes is the procedure of nanotechnology
application to biomedicine. Phospholipids have particular structural
conformation, leading to their self - assembly into bilayers with lipid chains inside
and polar head groups outside during hydration. Importantly, phospholipids are the
primary components of cell membranes so that liposomes have good biocompatibility
without toxicity. The formation of liposomes is almost spontaneous, wherein a
bottom - up procedure is involved [64] . When relatively free phospholipid molecules
meet water, their polar head groups have affi nity with water while lipid chains
repulse water, which subsequently leads to their aggregation due to hydrophobic
interaction, and then bilayers consisting of phospholipids are formed spontaneously.
Closed vesicles are further formed by bilayer bending (Figure 3 ). Before phospho-