Silk Encapsulated Films for Sustained Release of Buprenorphine.
Engelberg, Rachel Beth.
- A major problem with prescribed medication is patient compliance. In both the medical and veterinary field, physicians cannot be guaranteed that the patient will complete the prescribed regimen due to any number of factors. Buprenorphine (BUP) is a synthetic opioid with partial agonist and antagonist activity at the μ- and ORL- receptors and the κ- and δ- opioid receptors, respectively. BUP is use... read mored as an analgesic as well as a treatment for opiate addictions. Most analgesic or addiction treatment regimens tend to be inconvenient as they must be administered repeatedly for extended periods of time for any drug delivery route. With BUP, oral ingestion is not a desired route because the drug undergoes very high hepatic first-pass metabolism. For an oral administration of BUP, the desired dosage for the plasma must be increased tenfold, implying that 90% will become waste. For domesticated animals, there is no alternate route convenient for the pet owner. In humans on an outpatient basis, BUP is administered sublingually. For inpatient animals and humans, BUP can be administered intravenously, three times a day. In order to make BUP use more convenient and efficacious, a construct that will support zero-order, sustained release of BUP over an extended period of time must be developed. An encapsulated film-reservoir was constructed by infusing BUP within a film made from silk-fibroin. The film was then coated with differing numbers of silk layers to control the release profile of the drug. These film-reservoirs were assayed in vitro via PBS assays. Because BUP is a Schedule III drug and large quantities may not be procured for in vitro use, Indigo Carmine (IC) was used as an analog and underwent the same in vitro assays to demonstrate comparability. The release profiles were then determined for various mass loadings (0.25 mg, 1.25 mg, 2.50) and various numbers of coatings (0x, 4x, 8x). Drug release from coated silk constructs was then modeled for zero-order release. Indigo carmine did not demonstrate a significantly similar release profile to buprenorphine in vitro. Formulation of buprenorphine used and interactions between buprenorphine and silk require further investigations. Release profiles with increasing coating numbers demonstrated closer correlation to the kinetic model. The release profiles determined with these parameters were purely diffusion-based, however the addition of coatings approached zero-order release parameters when modeled. Mass loadings formed from indigo carmine in solution at a concentration of 5 mg/ml most closely followed the modeled profile. Films with 8x coatings demonstrated the slowest and most linear release kinetics.read less