Leonardus Kresna Widjaja

Hyaluronic acid-based nanocomposite hydrogels for ocular drug delivery applications

Hyaluronic acid (HA) is a widely investigated biomaterial for many therapeutic applications owing to its unique properties of biocompatibility, biodegradation, and viscoelasticity. HA being a natural component of eye tissue with significant role in wound healing is a natural choice as a carrier for ocular drug delivery, provided the incorporated drugs are released in a sustained manner. However, localized sustained release of drugs inside eye has been difficult to achieve because of the inability to retain carriers for long periods in the eye. Using noncrosslinked (soluble) HA offers limited control over site retention of drugs. In order to obtain prolonged sustained delivery, two HA-based composite hydrogels incorporating nanocarriers, have been synthesized and characterized for swelling, rheology, degradation, and in vitro release of latanoprost, a drug used to reduce intraocular pressure. The HA is first chemically modified, mixed with drug-loaded liposomes, and then crosslinked to obtain nanocomposite hydrogels. In vitro release study shows longer sustained release of latanoprost from composite hydrogels as compared to liposomes or hydrogels alone indicating additional resistance to drug diffusion because of the incorporation of liposomes inside the hydrogels. It is believed that these nanocomposite hydrogels, with controlled degradation properties and sustained release, could serve as potential drug delivery systems for many ocular diseases.

Thermoplastic biodegradable elastomers based on ε-caprolactone and l-lactide block co-polymers: A new synthetic approach

Although biodegradable polymers have found extensive application in medical devices, there are very few commercially available elastomeric biodegradable polymers. In this work, starting with the well-known monomers L-lactide and ε-caprolactone, we developed elastomers using a multiblock co-polymer approach. This ensures that the degradation products of such elastomers are also acceptable from a cytotoxicity standpoint. A series of polymers with various structures was synthesized utilizing a design of experiment approach. The basic structure is that of a diblock, with each block being modified by the addition of co-monomer. The synthesized polymers exhibited a range of mechanical properties from a typical thermoplastic polymer to that approaching a good thermoplastic elastomer. 13C nuclear magnetic resonance analysis, size exclusion chromatography and differential scanning calorimetry measurements have been utilized to relate the observed range of mechanical properties to the structure. In addition, the elastomeric nature has been established with the use of creep and recovery measurements. Such elastomers may find a variety of biomedical applications, ranging from stent coatings to atrial septal defect occluders.

Triblock copolymers of ε-caprolactone, L-lactide, and trimethylene carbonate: Biodegradability and elastomeric behavior†

For the triblock copolymer of ε-caprolactone, trimethylene carbonate, and L-lactide, where L-lactide blocks form the two ends, there is a range of compositions over which elastomeric behavior is obtained. Within this composition range, these polymers show good creep and recovery at ambient temperature, and exhibit high elongations to break. Additionally, we demonstrate that the recovery is independent of stress and strain for the elastomer compositions. The range of compositions that yield elastomeric character is rationalized based on the structure; specifically, there must be a minimum crystallinity of the end blocks and no crystallinity in the midblock, in addition to molar mass requirements. These polymers degrade by simple hydrolysis, and the rate of degradation is potentially programmable by manipulation of the molar ratio of hard segment to soft segment. Compared to biodegradable polyurethane, these polymers are expected to yield less harmful degradation products, and offer more variables for manipulation of properties. These polymers are also processable from the melt at temperatures exceeding about 130 °C. We expect to use these polymers in a variety of applications, including stent coatings, fully-degradable stents, and atrial septal defect occluders.