interactions between oppositely charged polyelectrolytes lead to the formation of
nanoparticles. The electrostatic interactions are instrumental in determining the
structure and function of living organisms, biopolymers, and drug delivery systems
(DDSs). Oppositely charged polyelectrolytes are capable of forming stable intermolecular complexes. The structures formed by opposite charges are normally more
stable than neutral block copolymers micelles dissociating upon dilution or with a
slight change in the external conditions. Grenha et al. [149] reported the preparation
of chitosan-based nanoparticle-loaded mannitol microspheres as a candidate to
transport therapeutic protein-loaded nanoparticles to the lungs. In this study,
BSA-loaded chitosan nanoparticles were first prepared by the interaction between
chitosan and TPP using an ionic gelation method. Next, these nanoparticles were
suspended in mannitol for spray-drying to form dry powders of BSA-loaded
chitosan/TPP nanoparticles. The distribution of chitosan nanoparticles and mannitol
in the microspheres was characterized using confocal laser scanning microscopy
(CLSM), X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass
spectroscopy. Zhang et al. [150] reported that polyionic hydrogels prepared by ionic
gelation have the advantage of creating an environment that favors the stabilization
of bioactive agents. In an another study, Fan et al. [151] reported the preparation of
monodisperse, low molecular weight (LMW) chitosan nanoparticles by a novel
method based on ionic gelation using TPP as a crosslinking agent. The objective
of this study was to solve the problem of preparation of chitosan/TPP nanoparticles
with a high degree of monodispersity and stability, and to investigate the effect of
various parameters on the formation of LMW chitosan/TPP nanoparticles. It was
found that the particle size distribution of the nanoparticles could be significantly
narrowed by a combination of decreasing the concentration of acetic acid and
reducing the ambient temperature during the crosslinking process. The optimized
nanoparticles exhibited a mean hydrodynamic diameter of 138 nm with a polydispersity index (PDI) of 0.026 and a zeta potential of +35 mV. The nanoparticles had
good storage stability at room temperature for up to at least 20 days. Katas and Alpar
[152] prepared chitosan nanoparticles using two methods of ionic crosslinking:
simple complexation and ionic gelation using TPP. Both methods produced
nanosized particles (<500 nm), depending on the type, molecular weight, and
concentration of chitosan. In the case of ionic gelation, the TPP weight ratio and
pH also affected the particle size. Papadimitriou et al. [113] demonstrated the
production of CS-g-PEG nanoparticles by the ionic gelation method using two
crosslinking agents, TPP and poly(glutamic acid) (PGA). According to them, no
other research has yet been published using PGA as ionic crosslinking agent for
CS-g-PEG nanomaterials in order to create protein nanocarriers. In brief, aqueous
CS-g-PEG solutions at different concentrations (0.5, 1.0, 1.5, and 2.0 mg/mL) were
first prepared at pH 3.5. Aqueous TPP or PGA (0.5 mg/mL final concentration) were
premixed with BSA stock solution (2 mg final drug amount to the samples) and then
added into the aqueous CS-g-PEG solutions at a rate of 1 mL/min. The obtained
nanoparticles were collected by centrifugation at 32,000 rpm for 50 min. Both the
crosslinking agents had a great influence on the particle size, although all nanoparticle samples showed a unimodal size distribution. It was found that a CS-g-PEG:TPP
108
J. Dutta
nanoparticles. The electrostatic interactions are instrumental in determining the
structure and function of living organisms, biopolymers, and drug delivery systems
(DDSs). Oppositely charged polyelectrolytes are capable of forming stable intermolecular complexes. The structures formed by opposite charges are normally more
stable than neutral block copolymers micelles dissociating upon dilution or with a
slight change in the external conditions. Grenha et al. [149] reported the preparation
of chitosan-based nanoparticle-loaded mannitol microspheres as a candidate to
transport therapeutic protein-loaded nanoparticles to the lungs. In this study,
BSA-loaded chitosan nanoparticles were first prepared by the interaction between
chitosan and TPP using an ionic gelation method. Next, these nanoparticles were
suspended in mannitol for spray-drying to form dry powders of BSA-loaded
chitosan/TPP nanoparticles. The distribution of chitosan nanoparticles and mannitol
in the microspheres was characterized using confocal laser scanning microscopy
(CLSM), X-ray photoelectron spectroscopy, and time-of-flight secondary ion mass
spectroscopy. Zhang et al. [150] reported that polyionic hydrogels prepared by ionic
gelation have the advantage of creating an environment that favors the stabilization
of bioactive agents. In an another study, Fan et al. [151] reported the preparation of
monodisperse, low molecular weight (LMW) chitosan nanoparticles by a novel
method based on ionic gelation using TPP as a crosslinking agent. The objective
of this study was to solve the problem of preparation of chitosan/TPP nanoparticles
with a high degree of monodispersity and stability, and to investigate the effect of
various parameters on the formation of LMW chitosan/TPP nanoparticles. It was
found that the particle size distribution of the nanoparticles could be significantly
narrowed by a combination of decreasing the concentration of acetic acid and
reducing the ambient temperature during the crosslinking process. The optimized
nanoparticles exhibited a mean hydrodynamic diameter of 138 nm with a polydispersity index (PDI) of 0.026 and a zeta potential of +35 mV. The nanoparticles had
good storage stability at room temperature for up to at least 20 days. Katas and Alpar
[152] prepared chitosan nanoparticles using two methods of ionic crosslinking:
simple complexation and ionic gelation using TPP. Both methods produced
nanosized particles (<500 nm), depending on the type, molecular weight, and
concentration of chitosan. In the case of ionic gelation, the TPP weight ratio and
pH also affected the particle size. Papadimitriou et al. [113] demonstrated the
production of CS-g-PEG nanoparticles by the ionic gelation method using two
crosslinking agents, TPP and poly(glutamic acid) (PGA). According to them, no
other research has yet been published using PGA as ionic crosslinking agent for
CS-g-PEG nanomaterials in order to create protein nanocarriers. In brief, aqueous
CS-g-PEG solutions at different concentrations (0.5, 1.0, 1.5, and 2.0 mg/mL) were
first prepared at pH 3.5. Aqueous TPP or PGA (0.5 mg/mL final concentration) were
premixed with BSA stock solution (2 mg final drug amount to the samples) and then
added into the aqueous CS-g-PEG solutions at a rate of 1 mL/min. The obtained
nanoparticles were collected by centrifugation at 32,000 rpm for 50 min. Both the
crosslinking agents had a great influence on the particle size, although all nanoparticle samples showed a unimodal size distribution. It was found that a CS-g-PEG:TPP
108
J. Dutta