422
R. Mankamna Kumari et al.
polymers and ionic surfactants such as polyethylene glycol (PEG) and polysorbate
20, 40, 60, and 80, respectively.
Cancer cells, unlike the normal cells have the ability to over-proliferate and overexpress cell surface receptors. Utilizing this property of overexpression of the cell
surface receptors NPs decorated with ligands could be implemented for the delivery of therapeutic molecules. The receptors mediate the uptake of the molecules via
receptor mediated endocytosis (Jain et al. 2011). This phenomenon is known as active
targeting. Although, the modified nanoformulations have improved targetability and
bioavailability, it is still a challenge to get sufficient amount of NPs around the target
region. There are several ligands that are employed for targeted delivery, such as
folic acid, transferrin, and biotin, including different polysaccharides and peptides.
For example, folate receptors are highly expressed in breast, ovarian, lung, uterine,
head and neck cancer. For this purpose, folic acid is used, which has 30 times more
affinity than any other folate derivatives. The particles are then taken up by the cell
by receptor-mediated endocytosis (Narayanan et al. 2010; Zhao et al. 2008). Similarly, transferrin receptors are overexpressed in glioblastoma which makes them an
attractive target for the use of transferrin as ligand molecules. It was noted that transferrin was highly expressed during malignancy due to higher requirement of DNA
synthesis for the proliferation of cells (Tortorella and Karagiannis 2014).
Besides its role in cancer therapeutics, PLGA nanoparticles are also implemented
for the treatment of other diseases including inflammatory diseases, neurodegenerative and infectious diseases. Gastrointestinal tract (GI) is known to be a complex organ
performing diverse functions such as digestion, absorption, and excretion. One of the
commonly prevailing diseases, inflammatory bowel disease (IBD) severely affects
any part of the GI tract causing improper functioning. The commonly used drugs for
its treatment are 5-aminosalicylic acid (5-ASA) or Mesalamine and immunosuppressive agents. However, the cure of the nanoparticles depends mainly on the intensity
of the disease and gives symptomatic relief. The disadvantages were overcome by
using nanoparticles via rectal administration. This showed higher bioavailability
and treatment efficacy (IBD). In another study, fluoromethalone loaded PLGA NPs
were developed for the treatment of inflammatory disease of eye. The formulation
showed ocular tolerance, anti-inflammatory efficacy and bioavailability. Further, it
showed greater penetration toward vitreous and higher anti-inflammatory effects
(Gonzalez-Pizarro et al. 2018).
Another group of diseases include neurodegenerative diseases characterized by
persistent loss of neuronal activity, which includes Alzheimers (AD) and Parkinsons
disease (PD). The prevalence of the disease has increased exponentially in the last
years. Their pathogenesis is mainly characterized by accumulation and aggregation
of proteins along with alterations and disturbances in tissue homeostasis (Farlow
2001; Kabanov and Gendelman 2007; Sahni et al. 2011; Tosi 2011). FDA approved
drugs: galantamine hydrobromide and memantine (MEM) are commonly prescribed
according to the degree and intensity of the disease. However, these formulations lack
efficacy. Galantamine loaded polymeric nanoparticles were synthesized to overcome
the disadvantages and were found to have less cytotoxicity at therapeutic dosage.
Similarly, in another study, MEM-PEG-PLGA NPs were synthesized against brain
R. Mankamna Kumari et al.
polymers and ionic surfactants such as polyethylene glycol (PEG) and polysorbate
20, 40, 60, and 80, respectively.
Cancer cells, unlike the normal cells have the ability to over-proliferate and overexpress cell surface receptors. Utilizing this property of overexpression of the cell
surface receptors NPs decorated with ligands could be implemented for the delivery of therapeutic molecules. The receptors mediate the uptake of the molecules via
receptor mediated endocytosis (Jain et al. 2011). This phenomenon is known as active
targeting. Although, the modified nanoformulations have improved targetability and
bioavailability, it is still a challenge to get sufficient amount of NPs around the target
region. There are several ligands that are employed for targeted delivery, such as
folic acid, transferrin, and biotin, including different polysaccharides and peptides.
For example, folate receptors are highly expressed in breast, ovarian, lung, uterine,
head and neck cancer. For this purpose, folic acid is used, which has 30 times more
affinity than any other folate derivatives. The particles are then taken up by the cell
by receptor-mediated endocytosis (Narayanan et al. 2010; Zhao et al. 2008). Similarly, transferrin receptors are overexpressed in glioblastoma which makes them an
attractive target for the use of transferrin as ligand molecules. It was noted that transferrin was highly expressed during malignancy due to higher requirement of DNA
synthesis for the proliferation of cells (Tortorella and Karagiannis 2014).
Besides its role in cancer therapeutics, PLGA nanoparticles are also implemented
for the treatment of other diseases including inflammatory diseases, neurodegenerative and infectious diseases. Gastrointestinal tract (GI) is known to be a complex organ
performing diverse functions such as digestion, absorption, and excretion. One of the
commonly prevailing diseases, inflammatory bowel disease (IBD) severely affects
any part of the GI tract causing improper functioning. The commonly used drugs for
its treatment are 5-aminosalicylic acid (5-ASA) or Mesalamine and immunosuppressive agents. However, the cure of the nanoparticles depends mainly on the intensity
of the disease and gives symptomatic relief. The disadvantages were overcome by
using nanoparticles via rectal administration. This showed higher bioavailability
and treatment efficacy (IBD). In another study, fluoromethalone loaded PLGA NPs
were developed for the treatment of inflammatory disease of eye. The formulation
showed ocular tolerance, anti-inflammatory efficacy and bioavailability. Further, it
showed greater penetration toward vitreous and higher anti-inflammatory effects
(Gonzalez-Pizarro et al. 2018).
Another group of diseases include neurodegenerative diseases characterized by
persistent loss of neuronal activity, which includes Alzheimers (AD) and Parkinsons
disease (PD). The prevalence of the disease has increased exponentially in the last
years. Their pathogenesis is mainly characterized by accumulation and aggregation
of proteins along with alterations and disturbances in tissue homeostasis (Farlow
2001; Kabanov and Gendelman 2007; Sahni et al. 2011; Tosi 2011). FDA approved
drugs: galantamine hydrobromide and memantine (MEM) are commonly prescribed
according to the degree and intensity of the disease. However, these formulations lack
efficacy. Galantamine loaded polymeric nanoparticles were synthesized to overcome
the disadvantages and were found to have less cytotoxicity at therapeutic dosage.
Similarly, in another study, MEM-PEG-PLGA NPs were synthesized against brain