Pharmaceutical Manufacturing Handbook: Production and

NATURAL BIODEGRADABLE POLYMERIC NANOPARTICLES 539
pH [11] . More monodisperse nanoparticles may be prepared using fractionated and
deacetylated chitosan [12] . In general, the size of nanoparticles will depend on the
molecular weight of chitosan, its concentration, and its surface charge [13] . The
physicochemical properties of chitosan are determined by the solution pH and ionic
strength [14] .
Gelatin Gelatin is obtained by either alkaline or acidic hydrolysis of collagen. It
has a triple helical structure with a high content of glycine, proline, and hydroxyproline
residues. Gelatin that is formed from alkaline treatment of collagen has
more carboxyl groups and a lower isoelectric point than that derived from acidic
hydrolysis [15] . The physicochemical properties of gelatin depend on the method
of extraction and the extent of thermal denaturation that occurs during the
purifi cation.
Gelatin nanoparticles can be prepared by various methods, including chemical
cross - linking, water - in - oil (w/o) emulsifi cation, and desolvation. Gelatin is cross -
linked with agents such as glutaraldehyde. Effi cient cross - linking usually results in
decreased rate of drug release. The w/o emulsifi cation involves extruding a preheated,
aqueous solution of gelatin into vegetable oils, such as corn or olive oils
[15] . The two - step desolvation method involves the dropwise addition of a water -
miscible nonsolvent such as acetone and ethanol [16] . While the use of collagen,
the parent compound of gelatin, in drug delivery is rare, collagen nanoparticles
have been used to deliver genes by exploiting the electrostatic interaction between
the positively charged polymer and negatively charged deoxyribonucleic acid
(DNA) [17] .
Polysaccharides The macromolecular polysaccharides that include pullulan,
mannan, and dextran are the main constituents of the cellular glycocalyx and play
an important role in cell – cell adhesion and the cell – cell recognition process [18] .
Pullulan is a nonimmunogenic, nontoxic, water - soluble, linear, nonionic polysaccharide
with α (1 – 4) and α (1 – 6) linkages with free hydroxyl groups for drug conjugation
[19] . Pullulans are intracellularly synthesized and secreted by a fungus,
Aureobasidium pullulans [20] . On the other hand, dextrans are anionic glucose
polymers derived from sucrose with α (1 – 6) glucosidic linkage. A class of enzymes,
glucansucrases, produced by two genera of lactic acid bacteria, namely, Leuconostoc
and Streptococcus, catalyze the synthesis of dextrans from sucrose. The extraction
of dextrans as well as their physical properties and drug delivery aspects has been
reviewed [21, 22] . When coated with mannans, the biological response of both
natural and synthetic polymeric nanoparticles may be changed [23] .
To make pullulan nanoparticles, the polymer must fi rst be made hydrophobic,
typically by conjugating alkyl groups, cholesterol groups, or succinyl groups. Hydrophobic
pullulans self - assemble to form stable hydrogel nanoparticles [24] . Alternately,
pullulan nanoparticles can be formed by cross - linking reverse micelles of the
polymer with glutaraldehyde [25] . Nanoparticles form when a solution of pullulan
acetate in N,N - dimethyl acetamide is used and dialyzed with borate buffer [26] .
Dextran is commonly conjugated to other polymers, such as PLGA, PEG,
polystyrene, and poly(methyl methacrylate) for preparation of nanoparticles.
Complex coacervation has been used to prepare dextran nanoparticles using
oppositely charged polymers such as polyethyleneimine [27] . Although nanoparticle