Biomaterial-Based Particulate Drug Carriers - Harnessing Biomaterials in Nanomedicine: Preparation, Toxicity, and Applications - page 15

treatment with free drugs as discussed in the introduction (see also
Figure 1.1). Formulating biologicals in carriers may conceivably
protect them along the GIT but needs careful consideration.
The carrier itself has to survive the GIT, which is a tough call for
biomaterial-based particulate drug carriers. The encapsulated
drug may leak out extensively during exposure of the drug-carrier
formulation to the acidic stomach environment. Similar to the
inability of particulate carriers — even if nano-sized — to get across
walls of intact blood vessels, particles are unable to gain access —
intact and with their drug load — from the GIT to the circulation.
Rather, particulate drug carriers administered orally are indicated
to act as site-adherent drug depots, allowing the drug itself to gain
access into the circulation [62-64].
To perform as drug depots in the GIT, there is no particular
advantage to using nano-sized particles. Micro-sized particles may
do better in terms of higher drug loads, slower particle degradation,
and slower drug loss.
Insulin is a key example, for itself and as a model for other
biologicals, for which oral delivery formulated in a particulate
carrier — from biological or synthetic materials — has been and is
actively pursued. Tested particles include hydrogels, microspheres,
nanoparticles, microemulsions, and liposomes, but unfortunately,
none has yet merited progression toward approved treatment
modalities [39, 62]. Yet, two examples from current ongoing studies
are encouraging. We have recently studied oral delivery of insulin
in two particulate carrier formulations, both of them micro-sized
and encapsulating insulin in a reversible-fibrillar form [39]. Both
formulations have hyaluronan on their surface, which turned out
to protect both carrier and encapsulated protein along the GIT, and
to perform in diabetic mice as a long-acting insulin formulation,
reducing blood glucose to satisfactory levels [39]. Another insulin
formulation in a particulate carrier, orally administered and peaking
at 5 h post administration, has advanced to clinical trials [65].
Thus, despite the difficulties of biomaterial-based drug carriers
for oral delivery of biologicals, the needs for such systems and
their attraction — for the patient and for improved therapy — are
sufficiently strong to drive extensive past and current research
eff orts. This is a particular area where pros and cons need to be tested
anew for each drug-carrier system, but hope should not dwindle, as
illustrated by the two examples cited above for insulin.