Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 547

The mole ratio of lactide to glycolide in the PLGA polymer can be modified, and
all such grades are commercially available. Increasing the amount of glycolide in the
polymer increases its rate of biodegradation. The components of the PLGA polymer,
poly(L-lactic acid) (L-PLA) and polyglycolic acid (PGA), have also been investigated
separately. Their degradation rate is very slow, leading to degradation times as long
as several years for L-PLA and several months for PGA. The lactide/glycolide copo-
lymers have shorter biodegradation times, on the order of several weeks [150,151] .
Hence, a broad spectrum of performance characteristics with these polymers has been
obtained by careful manipulation of four key variables [146] such as monomer stereo-
chemistry, comonomer ratio, polymer chain linearity, and polymer molecular weight.
Polymers along with a surfactant show more controlled release characteristics, as
observed in one study in which the protein release characteristics and cell adhesion
to a PLA and PLGA polymer membrane showed that the polymers along with surfac-
tant stabilizers have a more sustained effect on the release profile [152] . Large num-
bers of P/P such as lysozyme, leuprolide, myoglobulin, -galactosidase, cyclosporin,
and OVA have been incorporated in PLGA polymers and showed controlled release
profiles. Varying crystalline characters, range of hydrophilic behavior, and solubility
profiles are exhibited by different polymeric forms. These properties are ultimately
responsible for the biodegradation and release profiles. Crystalline domains and ste-
reo-irregularity inhibit the degradation of the polymer. Stereo-irregularity in lactides
thus determines the order of degradation time, that is:

Poly -lactide  Poly -lactide  Polyglycolide

L DL

( ,
stereo-irregular

crystalline (amorphous

stereo-irregular)

, (crystallin e

stereo-regular)

,

)

Polymers with higher molecular weight gave increasing viscosities to the solu-
tions and hence also affect the entrapment efficiency and the size of the microspheres
or nanoparticles and their sphericity [147] . Although PLGA polymers have proved
to be most promising degradable polymers, they are hydrophobic systems, and, con-
versely, hydrophilic polymers such as some biodegradable hydrogels and dextran
have offered advantages in protein loading [153] . Also proteins may degrade under
the acidic (pH 2) microenvironment of PLA/PLGA. A study has shown a rapid
degradration of BSA via aggregation and hydrolysis in PLGA microspheres, which
is consistent with other findings of acid denaturation of proteins.

11.4.2.2 �at﻽�a﻽ Po﻽ym��s
Despite the advent of synthetic biodegradable polymers, the use of natural biode-
gradable polymers to deliver drugs continues to be an area of active research. The
main attractions of natural polymers as excipients for drug delivery systems are they
are readily available, natural products of living organisms, capable of a multitude of
chemical modifications, and relatively cheap. Most investigations of natural poly-
mers as matrices in drug delivery systems have centered on proteins (e.g., collagen,
gelatin, and albumin) and polysaccharides (e.g., chitosan, starch, dextran, inulin, cel-
lulose, and hyaluronic acid) [147] .