Different Approaches to the Synthesis and Applications of Biomedical and Pharmaceutical Smart Biomaterials
thesisposted on 23.05.2021, 11:48 authored by Mohamed Mahmoud Khattab
In this study, two strategies were used to functionalize cellulose nanowhiskers. Firstly, by grafting its surface with β-cyclodextrin (βCD) for developing drug-nanocarrier. Secondly, by conjugating short polymer segments to its surface for reinforcing Poly(Ɛ-Caprolactone) (PCL), in order to develop nanocomposites with promoted properties suitable for regenerative medicine. In addition, the production and recovery of biodegradable bioplastics poly(3-hydroxybutyrate) (P(3HB)) from agro-industrial residues of hemp hurd biomass was also examined. In the first part, a drug-nanocarrier system based on βCD-grafted bacterial cellulose nanowhisker (BCNC-g-βCD) was developed as a prolonged drug release nanocarrier. Antibiotic Ciprofloxacin (CIP) and anticancer drugs; Doxorubicin (DOX) and Paclitaxel (PTX) were conjugated to BCNC-g-βCD as model drugs to form the drug-nanocarrier (BCNC-g-βCD-drug). Compared with un-grafted BCNC, the developed drug-nanocarrier showed significant increase in drug payloads from 495 ±4 to 810 ±7 µg/mg along with radical improvement in the drug release profiles. Initial burst releases was reduced significantly and prolonged and sustained release for (74.5–90%) of drug payload over 4–5.5 days were observed. In addition, an improved drug release performances were pragmatic in acidic pH of 6.4 that mimicked extracellular tumor cells. In vitro drug release data pointed to zero-order kinetic model with estimated zero-order release constants (K0) of 0.68, 0.74, and 0.79 µg drug/h (at pH 6.4, 37°C) for BCNC-g-βCD-CIP, BCNC-g-βCD-DOX and BCNC-g-βCD-PTX nanosystems, respectively. In the second part, the functionalized bacterial cellulose nanowhisker (BCNW-g-βCD-PCL2000) was synthesized. Reinforcing PCL matrix with 4 wt% of the functionalized nanowhisker resulted in bionanocomposite with promoted bulk properties. Compared to neat PCL, the obtained bionanocomposite showed 115% and 51% improvements in tensile strength and Young’s modulus, respectively; 20% increase in hydrophilicity; 7% increase in degradation rate; and 6% decrease in crystallinity. Gas foaming/combined particulate leaching technique is used to develop highly porous strutures having porosity of 86-95% and interconnected macropores with mean pore diameters of 250-420 µm. Porous scaffolds showed compression moduli values of 5.3-9.1 MPa in the range of cancellous bones. In the third part a dual-function PCL scaffold was fabricated. The envisioned drug-laden scaffold would provide adequate structural and mechanical supports for the newly regenerated tissues and simultaneously serve as localized drug delivery system. In this context, reinforced PCL with 4 wt% of BCNW-g-βCD-PCL2000 and 25 wt% of doxorubicin anticancer drug resulted in drugladen bionanocomposite of combined promoted bulk properties. Improvements of 165% and 107% in tensile strength and Young’s modulus, respectively; 31% in hydrophilicity; 10% in degradation rate; and 8°C increases in thermal stability. The obtained drug-laden porous scaffolds showed compressive moduli in the range of 7.2-12.3 MPa. In vitro drug releases fit the first-order release mechanism and occurred in a diffusion-controlled and sustained manner 60 days without obvious burst releases. The scaffolds will ultimately minimize systemic toxicities of drugs, lessen the number of dosing, and diminish the need for removal procedure. The forth study described prospective trials for greener production and extraction of the biodegradable bioplastics poly(3-hydroxybutyrate) P(3HB) from agro-industrial residues of hemp hurd biomass. Results showed that maximum hydrolysis yield of 72.4% was achieved by alkali pretreatment with 2% NaOH at 135°C for 60 min along with two-step enzymatic hydrolysis and ultrasonication. Total hydrolysate sugar concentration of 53.0 g/L was obtained. Under optimum conditions, total P(3HB) production of 13.4 g/L was achieved within 80 h of fermentation. Ultrasonic-assisted sodium dodecyl sulfate (SDS) has showed effectiveness as economic recovery method. It recovered bioplastics directly from the broth cell concentrate with P(3HB) content of 92%. Number average molecular weights (Mn) of recovered bioplastics were in the range of 150–270 kDa with polydispersity index (Mw/Mn) of 2.1–2.4.