Keratin hydrogels support the sustained release of bioactive ciprofloxacin

Abstract

Keratins are naturally derived proteins that can be fabricated into several biomaterial forms including hydrogels. These materials are a potential polymeric system for several tissue engineering and regenerative medicine applications due to their ability to support cell attachment, proliferation, and migration. However, little is known regarding their ability to support sustained release of therapeutic agents. This report describes the use of keratin hydrogels for sustained release of the antibiotic ciprofloxacin, which may prove useful to traumatic injury applications that would benefit from materials promoting tissue regeneration while also preventing acute infection. Hydrogels were formed from keratins obtained by oxidative extraction and known as keratose. We found that keratose hydrogels released ~60% of loaded ciprofloxacin over the first 10 days and that continued release was detectable over the course of 3 weeks. Released ciprofloxacin was bioactive, inhibiting growth of Staphylococcus aureus for 23 days in vitro and for 2 weeks in a mouse subcutaneous model. The rate of ciprofloxacin release was highly correlated with degradation of the keratin hydrogel and not consistent with simple diffusion. Further experiments indicated that ciprofloxacin binds to keratose through electrostatic interactions. These studies demonstrate the specific use of keratose hydrogels for the release of antibiotic and the potential for the more general use of this material in tissue engineering and regenerative medicine applications.

Ciprofloxacin-Loaded Keratin Hydrogels PreventPseudomonas aeruginosaInfection and Support Healing in a Porcine Full-Thickness Excisional Wound

“…18,22,25 Compared to materials that release drugs simply via diffusion and are known to display a short burst of antibiotic release, keratose hydrogels have been shown to support the sustained release of the antibiotic ciprofloxacin for > 1 week in vitro. 23 Further, keratose hydrogels loaded with 2 mg/mL ciprofloxacin inhibit S. aureus growth for 23 days in vitro. 23 The purpose of this study was to test the ability of ciprofloxacin-loaded keratose hydrogels to inhibit P. aeruginosa growth both in vitro and in vivo.…”

“…[19][20][21][22] Specifically, keratin hydrogels are advantageous over alternative dressings because they elicit minimal foreign body responses, possess tunable mechanical properties, and are capable of serving as sustained-release delivery vehicles. 18,22,23 Additionally, keratins are unique as antibiotic carriers for infection control in that they are susceptible to enzymatic degradation by cutaneous bacteria that produce keratinases. 24 Given that mammals possess no natural mechanisms for proteolytic degradation of keratin, this feature provides a mechanism of tailored antibiotic release kinetics where more infected wounds degrade the carrier faster and release more drug to combat the infection.…”

Keratin Protein-Catalyzed Nitroaldol (Henry) Reaction and Comparison with Other Biopolymers

“…Aromatic aldehydes bearing strong electron-withdrawing substituents were easily converted in DMSO into the corresponding β-nitroalcohols 3a-f in excellent yields regardless the position of the substituent (ortho-, meta-, para-) ( Table 2, entries 1-6). Weaker acceptor substituents afforded the corresponding product 3 in moderate yields (Table 2, entries 7,8,10,12,15). Interestingly, here the meta-position (Table 2, entry 9) of the substituent seemed to be more favored, giving rise to 3i in good yield and twice as much than the para-substituted substrate ( With these preliminary results in hand, we examined the substrate scope of the reaction using different aldehydes in combination with nitromethane or nitroethane both in DMSO (Table 2) and H 2 O/TBAB (Table 3) at room temperature.…”

“…The complete amino acid sequence of keratins obtained from different sources has been reported in several publications [4][5][6][7], making the protein a suitable candidate to be tested as a catalyst. Recently, keratinous materials have attracted increasing attention as an important source of renewable biomaterials, especially since keratin wastes have been estimated to be more than 5 million tons per year [8], being used after degradation for different applications including scaffolds for tissue engineering [9,10] and support matrices for catalytic metal nanoparticles [11], among others [12].…”

The Pharmacology of Regenerative Medicine

“…However, this property may be useful in not only allowing the scaffold matrix to remain in place for various lengths of time (as desired and designed) but may also be useful in terms of drug delivery. In fact, a number of different materials are known to achieve release of therapeutic agents (small molecule drugs or growth factors) not through diffusion but through degradation of the scaffold material (Saul et al, 2011).…”