Pharmaceutical Manufacturing Handbook: Production and

538 BIODEGRADABLE NANOPARTICLES
Some natural polymers may be chemically modifi ed to tailor solubility properties.
An example is the reaction of the free amino groups of chitosan to form the more
water soluble derivative, methoxy - polyethylene glycol (PEG) chitosan [3] . Collagen
is marketed as six different types, I – VI, depending on its source and physiological
applicability. Similarly, the properties of gelatin are dependent on the method of
preparation using acid - or base - catalyzed hydrolysis from collagen.
5.4.2.1 Physical Properties of Natural Polymers and Methods Used to
Prepare Nanoparticles
Sodium Alginate Alginates are primarily derived from the algae Macrocystis pyrifera
and Laminaria hyperborea . These are linear, unbranched polymers containing
β - (1 – 4) - linked mannuronic acid and α - (1 – 4) - linked guluronic acid residues that are
either arranged in blocks, commonly called G blocks and M blocks, or alternate with
each other. Alginates are hydrophilic, anionic polymers that vary in molecular
weight, depending primarily on the G and M blocks. They are characterized by the
ratio of guluronic and mannuronic acids, which can be quantifi ed by ultraviolet
(UV) spectrophotometry, gas chromatography, and high - performance liquid chromatography
(HPLC) [4] . For example, the polymer obtained from M. pyrifera has
an M/G ratio of 1.6. Alginate obtained from seaweed must be purifi ed by one of
several applicable alkali and acid treatment protocols [5, 6] .
Alginate nanoparticles can be prepared using ionotropic gelation, emulsifi cation/internal
gelation, and emulsifi cation/solidifi cation methods. Ionotropic gelation
results when the anionic alginate reacts with cationic ions or molecules such as
calcium or poly - l - lysine. Gelation occurs when cations chelate the guluronic and
mannuronic acid groups to produce an “ egg - box ” structure that encapsulates the
drug. The size of the alginate particles is determined by the molar concentration of
calcium or poly - l - lysine and the method of addition of these counterions to alginate
[7] . In the emulsifi cation/internal gelation method, the sodium alginate and an
insoluble calcium salt are dispersed in a vegetable oil and the calcium ions are liberated
to form an alginate gel when the pH of the dispersion is lowered [8, 9] . An
advantage of the use of alginate polymers to deliver drugs is that nanoparticles are
prepared in aqueous media and may be more suitable to formulate compounds that
are unstable in organic solvents such as proteins and peptides. However, since the
chelation to form the gel is reversible, a disadvantage of unmodifi ed, alginate - based
delivery systems is rapid drug release due to the collapse of the egg - box structure
when exposed to monovalent ions in physiological media.
Chitosan Chitosan is a nontoxic, biodegradable polymer obtained by hydrolysis
of chitin, a natural polysaccharide that is a chief component of the crustacean exoskeleton.
Unmodifi ed chitosan is soluble in acidic media and has signifi cant mucoadhesive
properties.
Chitosan nanoparticles may be prepared using various methods, including emulsion
cross - linking, coacervation – precipitation, spray drying, emulsion droplet
coalescence, ionic gelation, reverse - micellar method, and sieving. A relatively recent
review describes the methods and applications of chitosan nanoparticles in drug
delivery [10] . Chitosan nanoparticles have also been prepared using water - soluble
cross - linking agents such as carbodiimide with the size being controlled by changing