Gelatin, which forms thicker gel matrices, usually is associated with a much
longer and sustained drug release profile. In a phase II clinical trial, an improved
angiogenesis was seen in patients with critical limb ischemia, with a sustained
release of fibroblast growth factor (FGF) from gelatin carrier gels [95]. The most
important parameter that affects drug release from gelatin hydrogels is the degree of
crosslinking, which in turn affects parameters such as degradation rate, thickness of
the gel, and diffusion of the drug [96, 97]. Another study demonstrated the
sustained release of human growth hormone (hGH) from collagen thin films, aiding
better wound healing in db/db mice. From the collagen film prepared by air drying,
hGH was secreted for 3 days in a sustained manner, resulting in better wound
healing with a single administration of the therapeutic [98]. This apart, gelatin and
modified gelatin (thiol, PEG) in nanoparticulate form has demonstrated good
success in the delivery of various hydrophobic and hydrophilic drugs as well as
for intracellular DNA delivery [99–101]. The degree of crosslinking and the
hydrophilicity of gelatin regulated the release of the drugs from within the matrix.
Unlike other proteins, caseins and whey proteins are mainly administered orally.
Hence, drug release from these carriers mainly depends upon the digestion of the
carrier, which is usually a rapid process [74]. Casein and whey proteins form
matrices that protect the drugs from the harsh environment of the stomach and
intestine.
2.3 Stability of Nanocarriers
The most important consideration in developing a pharmaceutical formulation is its
long-term stability, which is important from two different viewpoints: (1) stability
of the nanocarriers during storage as well as in vivo and (2) stability conferred by
the nanocarrier to the loaded drug. In both situations, the chemical structure of the
parent molecule, the extent of crosslinking, and the physical integrity of the drug
and nanocarrier should be intact for a long time during storage and inside the host
environment. This is a great obstacle when considering a translation of
nanoformulations for clinical applications and, hence, it is essential to devise new
strategies to alleviate these issues. The stability of nanoformulations is estimated by
assessing the influence of temperature and humidity on various parameters such as
particle size, zeta potential, drug content, viscosity, pH, etc. Biological stability, i.e.
the ability of the matrix to confer sustained release even when exposed to a harsh
environment containing degrading enzymes, is also an important concern that needs
to be addressed.
2.3.1 Stability of Carbohydrates
To solve the issues related to the physical instability of carbohydrate nanocarriers,
appropriate surface modification, for example glycosylation, seems to be one of the
promising strategies [86, 87]. Likewise, for addressing biological instability issues,
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D. Narayanan et al.
longer and sustained drug release profile. In a phase II clinical trial, an improved
angiogenesis was seen in patients with critical limb ischemia, with a sustained
release of fibroblast growth factor (FGF) from gelatin carrier gels [95]. The most
important parameter that affects drug release from gelatin hydrogels is the degree of
crosslinking, which in turn affects parameters such as degradation rate, thickness of
the gel, and diffusion of the drug [96, 97]. Another study demonstrated the
sustained release of human growth hormone (hGH) from collagen thin films, aiding
better wound healing in db/db mice. From the collagen film prepared by air drying,
hGH was secreted for 3 days in a sustained manner, resulting in better wound
healing with a single administration of the therapeutic [98]. This apart, gelatin and
modified gelatin (thiol, PEG) in nanoparticulate form has demonstrated good
success in the delivery of various hydrophobic and hydrophilic drugs as well as
for intracellular DNA delivery [99–101]. The degree of crosslinking and the
hydrophilicity of gelatin regulated the release of the drugs from within the matrix.
Unlike other proteins, caseins and whey proteins are mainly administered orally.
Hence, drug release from these carriers mainly depends upon the digestion of the
carrier, which is usually a rapid process [74]. Casein and whey proteins form
matrices that protect the drugs from the harsh environment of the stomach and
intestine.
2.3 Stability of Nanocarriers
The most important consideration in developing a pharmaceutical formulation is its
long-term stability, which is important from two different viewpoints: (1) stability
of the nanocarriers during storage as well as in vivo and (2) stability conferred by
the nanocarrier to the loaded drug. In both situations, the chemical structure of the
parent molecule, the extent of crosslinking, and the physical integrity of the drug
and nanocarrier should be intact for a long time during storage and inside the host
environment. This is a great obstacle when considering a translation of
nanoformulations for clinical applications and, hence, it is essential to devise new
strategies to alleviate these issues. The stability of nanoformulations is estimated by
assessing the influence of temperature and humidity on various parameters such as
particle size, zeta potential, drug content, viscosity, pH, etc. Biological stability, i.e.
the ability of the matrix to confer sustained release even when exposed to a harsh
environment containing degrading enzymes, is also an important concern that needs
to be addressed.
2.3.1 Stability of Carbohydrates
To solve the issues related to the physical instability of carbohydrate nanocarriers,
appropriate surface modification, for example glycosylation, seems to be one of the
promising strategies [86, 87]. Likewise, for addressing biological instability issues,
252
D. Narayanan et al.