6.3 Poly(lactic acid-co-glycolic acid)
Polymeric materials based on PLGA, a copolymer of lactide and glycolide, are
widely used for biomedical and pharmaceutical applications. PLGA nanoparticles
have been considered for sustained and targeted delivery of different compounds,
including drugs, proteins, bioactive materials, and plasmid DNA [131, 132]. PLGA
is easily biodegraded into lactic acid and glycolic acid in the physiological system as
result of hydrolysis of the ester linkages in the presence of water; these are then
excreted from the body naturally [133]. The biodegradation rate, crystallinity, and
mechanical properties of PLGA can be manipulated by controlling the unit ratio of
lactide to glycolide and the overall molecular weight of the copolymer. Surface
modifications, additives, molecular weight, and processing conditions of PLGA also
influence the effective response to formulated nanomedicines [134]. The composition ratio affects the binding capability of drugs and other active compounds with
PLGA due to physicochemical properties [100]. Several cancer-related drugs such
as paclitaxel, doxorubicin, 5-fluorouracil, 9-nitrocamptothecin, and cisplatin have
been incorporated in PLGA nanoparticles and successfully delivered in vivo [135].
The surface charge of the nanoparticles is important for the cellular internalization of
nanoparticles, clustering in blood flow, adherence, and interaction with oppositely
charged cell membranes [136]. Formulations using some additive to the PLGA
nanoparticles have shown reasonably good activity and much faster administration
in comparison to traditional formulations [84]. The incorporation of paclitaxel in the
PLGA nanoparticles strongly enhances its antitumoral efficacy as compared to free
drug. The controlled delivery of cisplatin in encapsulated PLGA–methoxypoly
(ethylene glycol) (mPEG) nanoparticles to tumor cells significantly reduces drug
toxicity and improves its therapeutic index. Xanthone, an inhibitory drug for cancer
cell lines, has been loaded into PLGA nanoparticles and shown to be physically
stable for 3–4 months with sustained release of xanthone [104]. Rose Bengal, which
is useful for the treatment of melanoma cancer cells, has been successfully entrapped
into PLGA nanoparticles and about 50% of drug release was measured within 30 min
in serum [137]. Triptorelin-loaded PLGA nanospheres have been prepared with an
encapsulation efficiency varying from 4 to 83% for the treatment of sex-hormonedependent tumors [138]. High encapsulation efficiency was explained by an ionic
interaction occurring between the peptide and the copolymer. Dexamethasone,
which reduces the inflammatory response of the body, has been incorporated into
PLGA (75:25) nanoparticles and was completely released from this formulation
after 4 h of incubation at 37
o C in vitro [80]. Similarly, insulin-, haloperidol-, and
estradiol-loaded PLGA nanoparticles have been prepared with high encapsulation
efficiency and used for therapy of the relevant diseases [92, 134].
6.4 Poly(e-caprolactone)
PCL is a semicrystalline polyester (T g about À60
C, T m ~60
C) that is synthesized
by ring-opening polymerization (ROP) of E-caprolactone and is degraded through
Biodegradable Polymers for Potential Delivery Systems for Therapeutics
187
Polymeric materials based on PLGA, a copolymer of lactide and glycolide, are
widely used for biomedical and pharmaceutical applications. PLGA nanoparticles
have been considered for sustained and targeted delivery of different compounds,
including drugs, proteins, bioactive materials, and plasmid DNA [131, 132]. PLGA
is easily biodegraded into lactic acid and glycolic acid in the physiological system as
result of hydrolysis of the ester linkages in the presence of water; these are then
excreted from the body naturally [133]. The biodegradation rate, crystallinity, and
mechanical properties of PLGA can be manipulated by controlling the unit ratio of
lactide to glycolide and the overall molecular weight of the copolymer. Surface
modifications, additives, molecular weight, and processing conditions of PLGA also
influence the effective response to formulated nanomedicines [134]. The composition ratio affects the binding capability of drugs and other active compounds with
PLGA due to physicochemical properties [100]. Several cancer-related drugs such
as paclitaxel, doxorubicin, 5-fluorouracil, 9-nitrocamptothecin, and cisplatin have
been incorporated in PLGA nanoparticles and successfully delivered in vivo [135].
The surface charge of the nanoparticles is important for the cellular internalization of
nanoparticles, clustering in blood flow, adherence, and interaction with oppositely
charged cell membranes [136]. Formulations using some additive to the PLGA
nanoparticles have shown reasonably good activity and much faster administration
in comparison to traditional formulations [84]. The incorporation of paclitaxel in the
PLGA nanoparticles strongly enhances its antitumoral efficacy as compared to free
drug. The controlled delivery of cisplatin in encapsulated PLGA–methoxypoly
(ethylene glycol) (mPEG) nanoparticles to tumor cells significantly reduces drug
toxicity and improves its therapeutic index. Xanthone, an inhibitory drug for cancer
cell lines, has been loaded into PLGA nanoparticles and shown to be physically
stable for 3–4 months with sustained release of xanthone [104]. Rose Bengal, which
is useful for the treatment of melanoma cancer cells, has been successfully entrapped
into PLGA nanoparticles and about 50% of drug release was measured within 30 min
in serum [137]. Triptorelin-loaded PLGA nanospheres have been prepared with an
encapsulation efficiency varying from 4 to 83% for the treatment of sex-hormonedependent tumors [138]. High encapsulation efficiency was explained by an ionic
interaction occurring between the peptide and the copolymer. Dexamethasone,
which reduces the inflammatory response of the body, has been incorporated into
PLGA (75:25) nanoparticles and was completely released from this formulation
after 4 h of incubation at 37
o C in vitro [80]. Similarly, insulin-, haloperidol-, and
estradiol-loaded PLGA nanoparticles have been prepared with high encapsulation
efficiency and used for therapy of the relevant diseases [92, 134].
6.4 Poly(e-caprolactone)
PCL is a semicrystalline polyester (T g about À60
C, T m ~60
C) that is synthesized
by ring-opening polymerization (ROP) of E-caprolactone and is degraded through
Biodegradable Polymers for Potential Delivery Systems for Therapeutics
187