Controlled Molecular Release through Polymeric Vehicle

Laha, Anindita and Majumdar, Saptarshi (2018) Controlled Molecular Release through Polymeric Vehicle. PhD thesis, Indian Institute of Technology, Hyderabad.

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Abstract

Controlled drug delivery systems (DDS) have gained a lot of attention recently due to their added advantages such as improving therapeutic efficacy in delivering the drug molecules at a predetermined rate to the targeted site for a prolonged period. Designing a polymer based DDS involves an in-depth understanding of drug-carrier interactions, and good control over the parameters that can modulate transportation of drug molecules according to the therapeutic requirement. Delivering less soluble drug molecules encapsulated in hydrophilic polymer matrix in zero-order manner is usually a challenge. To counter this challenge, we used Piperine, a model hydrophobic drug and Amphotericin B (Amp-B), a model amphiphilic drug in order to develop a polymer based DDS. We also used FDA approved natural polymer gelatin (type A) as an excipient because of its biocompatibility, biodegradability, muco-adhesiveness and easy availability. Despite of all the advantages of gelatin, it is extremely hydrophilic and has poor mechanical stability in an aqueous solution that limits its application and long-term usage. To overcome this challenge, we used Glutaraldehyde (GTA) as a crosslinker to modify gelatin. Although GTA is widely used as a crosslinker because of its excellent efficiency in stabilizing collagenous material, higher concentration of GTA solution (25 % v/v) and longer exposure in saturated vapor of GTA (more than 24 h as reported in literature) may have adverse cytotoxic effects. We successfully used a highly diluted concentration of GTA solution (0.01-0.25 % v/v) and reduced the exposure time to only 6 minute to saturated GTA vapor for crosslinking to achieve the desired stability of the fabric. In summary, this thesis investigates the full potential of natural polymer (gelatin, type A) based cast-film (GCF) and electrospun nanofiber film (GNF) as DDS, particularly for less soluble drug molecules.

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