Parenteral Delivery of Peptides and Proteins - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 554

A peptide or protein drug can be formulated into an implant by standard tableting or
compression techniques. Certain lipid materials can be directly mixed with the peptide
or protein drug to form these implants [199] . A wide variety of polymers have been
investigated for this approach. Biodegradable polymers are the most suitable and most
widely used material because they eliminate the need for resurgery to remove implants.
PLGA is the most studied and acceptable polymer for this purpose; these also have a
long history of use as biodegradable sutures and in drug delivery systems. Implantable
drug delivery systems of biocompatible polymers, such as EVAc, silicone [200] , cel-
lulose acetate, and polymethylmethacrylate (PMMA) [201] , also have been studied.
These implant devices release drugs with zero order kinetics for an extended period of
time, which is desirable. However, these devices must be surgically implanted and, in
some cases, surgically removed too. Consequent disadvantages of using these implants
include patient discomfort, possibility of infection, and high medical costs [202,203] .
Table 11.4 summarizes details of various marketed implants of proteins and peptides.
A novel approach for an injectable implant is in situ forming parenteral drug deliv-
ery systems (ISFPD) [211-217] . These controlled release liquid systems are injected
subcutaneously or intramuscularly and transform to semisolid or solid matrices
when in contact with aqueous fluids of the body or release media. Polymers and
copolymers such as polylactides, polyglycolides, or PLGA that are soluble in organic
solvents and insoluble in water are able to form solid matrices and thus are very suit-
able for such systems. In one study, ISFPD showed constant “infusion-like” plasma

Table 11.4 List of Marketed Implants of P/P Drugs along with Their
Characteristic Features

Marketed Implants Characteristics Features Reference

Zoladex ® —goserelin
acetate

Sterile, biodegradable, PLGA copolymeric, 1.5 mm
diameter, cylindrical shaped, preloaded in a special
single-use syringe with a 14G needle, administered
every 12 weeks for treatment of prostatic carcinoma

[204]

L-asparaginase Immobilized in spherical polyacrylamide microparticles,

which have been inserted in polyacrylamide gel for
implantation in rats

[205]

Vasopressin Polypropylene/collodion device. Showed decrease in

urine production for at least 50 days when implanted
subcutaneously in vasopressin-deficient Brattleboro
rats

[206,207]

Nafarelin PLGA implants, studied both in vivo and in vitro .

A triphasic release profile was observed as in the
case of microspheres. The release profile could be
controlled by modifying the physical properties of the
polymer, such as molecular weight or the ratio of the
more hydrophobic lactic acid monomer to the less-
hydrophobic glycolic acid monomer

[208]

Duros ® —
somatotropin

Design based on the success of the Alzet osmotic pump
in laboratory animals

[209]