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Abstract The candidates own work aims at creation of innovative systems for application in medical domains notably drug delivery and wound healing. Such systems are based on nano-sized carbohydrate polymer. For convenience the work is divided into six chapters dealing with the preparation, characterization and utilization of these systems in medical domains are summarized under. Chapter 1: Ultra-Microstructural features of perborate oxidized starch Oxidation of native maize starch (NS) using Sodium perborate at these different concentrations yields three levels of oxidized starches. The latter include low-, medium-, and highly oxidized starches; nominated as LOS, MOS and HOS respectively. The ultrafine structures of these oxidized starches along with native starch were monitored using world - class facilities. Results obtained bring into focus conclusions given under: (a) The FT-IR and X-ray diffraction patterns indicate the creation of carbonyl groups and a decrease in the crystalinity shape of starch during oxidation; in accordance with the results of carbonyl and carboxyl groups obtained through chemical analysis. b) The oxidized starches display increased solubility and decreased apparent viscosity – vis-à-vis - native starch upon increasing the extent of oxidation. (c) The resultant oxidized starches have greater uniformity, display greater thermal stability than the native maize starch, and follows the order: HOS > MOS > LOS > NS when all these substrates are subjected to thermal gravimetric analysis. (d) High-resolution scanning electron microscopy clarify that the surfaces of oxidized starches became rough and the edges lost completely their definiteness upon oxidation. (e) The marginal amount of the residual components of SPB after repeated washing in the resultant HOS powder was found. The above ultra-microstructural features of oxidized starches brought about by treating native maize starch with sodium perborate advocate their use in different applications. Of these, we have indeed used with great success the perborate- oxidized starches in textile warp sizing on industrial scale. Their use in the medical domains is in progress. Chapter 2: Ultra-fine characteristics of Starch Nanoparticles Prepared Using Native Starch and Oxidized Starches With and Without Surfactant Current work addressed two main objectives. The first was to establish a simple and reproducible method for synthesis of starch nanoparticles. This objective could be fulfilled through modification of the nanoprecipitation method by using alkaline aqueous solution as the solvent and ethanol as precipitant; ethanol was added drop-wise to the starch paste solution. The second objective was to verify differences in ultrafine characteristics of St-NPs prepared using native starch vis-à-vis those obtained using low, medium and high oxidized starches using world class facilities. Main conclusions arrived from these investigation are given below. 1. TEM, particle size analyzer and polydispersity index (PDI) confirmed the successful synthesis of spherical starch nanoparticles within the range 135-155 nm with PDI value 0.333 before the addition of surfactant (Tween® 80). 2. FT-IR and X-ray diffractograms provide evidence that the chemical structure of Starch nanoparticles have the same structure of the unmodified native starch. 3. TGA reveals that, the thermal stability of starch nanoparticles are higher than native starch. Furthermore, the surface charge of starch nanoparticles are higher than the native starch but still have low stability. 4. The optimum conditions for preparation of starch nanoparticles was 5 g NS, along with 30% NaOH (OWS), total volume 100 ml H2O; 100 ml absolute ethanol, Temperature 25C. 5. After the addition of 20 % Tween® 80 (OWS) before precipitation the particle size decreases dramatically to reach a value 103 nm which still in good dispersion. 6. The FT-IR and XRD of starch nanoparticles coated with and without Tween® 80 have the same function groups without any minor shift in the wavelength indicating that there is no chemical reaction between starch and the surfactant. 7. The particle size evaluated for the three oxidized starches nanoparticles by DLS and TEM significantly decreased following the order HOSt-NPs < MOSt-NPs < LOSt-NPs. 8. The particle size of highly oxidized starch nanoparticles has the smallest size and reaches 22 nm with good polydispersity. 9. The stability of highly oxidized starch is higher than that of starch nanoparticles, in conformation with zeta potential. It is expected that, these native and oxidized starches in the nanoform will have potential applications in medical domains, particularly for drug carrier. Chapter 3: Development of new system based on crosslinked starch nanoparticles for diclofenac sodium delivery Current work presents a manifold study aiming at development of a promising and controlled release transdermal delivery system to enhance the therapeutic efficiency of diclofenac sodium (DS). The system is based on crosslinked starch nanoparticles which were synthesized using native starch (NS) and oxidized starches derived thereof. The oxidized starches comprised low, medium and highly oxidized starches that could be abbreviated as LOS, MOS and HOS, respectively. Crosslinking was effected by reacting sodium tripolyphosphate (TPP) at different concentrations. Crosslinked starch nanoparticles loaded with DS were synthesized according to the nanoprecipitation method using different DS concentrations. A two-level factorial design were practiced for prediction of optimized formulation for DS loaded crosslinked starch nanoparticles. At this end, the optimized formulation was applied to LOS, MOS and HOS. The formulated nanospheres were systematically studied by monitoring drug loading, entrapment efficiency, transmission electron microscopy (TEM), particle size analyzer, polydispersity index (PDI) and zeta potential for shape and surface characteristics and in vitro release studies. Physicochemical characterization and analysis of the formulated nanosphares were also excercized using fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and Differential scanning caliorimetry (DSC) to determine the fine physical nature (crystallinity), thermal behaviour and possible occurrence of interaction between DS and the crosslinked starch nanoparticles. Interaction of crosslinked starch nanoparticles with DS causes profound changes in the crystalline structure of DS; DS is completely converted to amorphous structure. Application of experimental In vivo targeting efficiency of the optimum formula of crosslinked nanoparticles of NS, LOS, MOS and HOS with TPP and loaded with DS were examined histopathologically in skin irritation of healthy rats. Obviously, then, the essential target of the work could be successfully achieved. Application of experimental design allowed the optimization of different factors to yield spherical nanoparticles with small particle size, low polydispersity index and high entrapment efficiency and sustained release for DS drug. The histophathological studies on rat skin advocate the use of the designed transdermal DS loaded crosslinked starch and medium oxidized starch nanoparticles formulations as they are safe and non-irritant to rat skin. This would render the designed formulation a safe, highly effective, controlled and convenient mean of therapy with the non-steroidal anti-inflammatory drug (NSAIDs). Chapter 4: New Formulation of Indomethacin and Acyclovir Based on Crosslinked Starch Nanoparticles for Controlled Drug Delivery Polymeric nanoparticles which posess a better reproducibility and stability profile than other carrier like microparticles have been studied as alternative drug carrier. An eco-friendly nanoprecipitation technique was put forward to synthesize native and oxidized starches nanoparticles loaded with insoluble drugs such as Indomethacin (IND) and Acyclovir (ACV) nanoparticles were also loaded onto crosslinked starch nanoparticles. Factors studied to find out the optimum conditions were selected through factorial design for preparation of different formulations of crosslinked starch nanoparticles. Major parameters studied 20 mg, 50mg drug concentration and 0.5, 1g TPP Concentration while the concentration of starch and surfactant were kept constant. World-class facilities were used for evaluation as in the case of diclofenac sodium. The results obtained indicated that (a) the best formula for IND loaded starch nanoparticles with small spherical size and PDI, high zeta potential, high entrapment efficiency and controlled release was at 0.5 g TPP and 20 mg IND. On the other hand, the best formula for ACV loaded starch nanoparticles was at o.5 g TPP and 50 mg ACV. (b) FT-IR, XRD and DSC indicated that there is no chemical interaction between crosslinked starch nanoparticles and drug (IND or ACV). (c) Entrapment efficiency and in vitro release of drugs from crosslinked starch nanoparticles followed the order: Native> Low oxidized> Medium oxidized> highly oxidized starch. The results obtained could be attributed to the dependence of the in vitro release rate of IND and ACV on the viscosity of starch and oxidized starches when native starch have higher holding capacity and entrapment efficiency for loading the drugs under investigation. Chapter 5: Nanostructural features of silver nanoparticles powder synthesized through concurrent formation of the nano-sized particles of both starch and silver For the first time, powdered starch-silver nanoparticles were synthesized having highly concentrated AgNPs with extremely small sizes by using modified nano-precipitation method. In particular, we describe an environment friendly one-step method to synthesize powdered AgNPs. This was done by reduction of AgNO3 solution using alkali dissolved starch meanwhile the latter acted as stabilizing agent for the formed AgNPs. Ultimately, the AgNPs in the colloidal solution were coated with starch were precipitated using the least amount of ethyl alcohol as precipitating agent. This green approach may find various medicinal applications (e.g. wound healing) as well as technological applications. Chapter 6: More Insight on characterization of Nanosized Particles of Silver Powder and their Application in Antimicrobial Wound Dressing and Anti-inflammatory Efficacy Powdered silver nanoparticles and highly concentrated solutions of AgNPs using alkali dissolved starch which act the dual role: as reduction for Ag+ and stabilizer for AgNPs formed thereof. AgNPs colloidal solution having different concentrations (60, 125 and 250 ppm) was prepared from stock solution having highly concentration 30000 ppm AgNPs. The AgNPs colloidal solutions were used for treatment of cotton fabrics as per the pad-dry-cure technique. Cotton fabrics loaded with these three different concentrations of AgNPs colloidal solutions were evaluated for various medical applications, namely, antimicrobial, wound healing, anti-inflammatory as well as toxicity. The antimicrobial efficacy of dressing containing 250 ppm AgNPs was more effective against microorganisms including bacteria and fungi than that of dressing containing 60 and 125 ppm as indicated by the inhibition zone. The wound healing of dressing containing the highest content of AgNPs (250 ppm) acquire the greatest potent healing which is nearly similar to the controlled cream (Dermazin). It was also found that wound healing is intimately linked to inflammation in normal circumstances as various inflammatory mediators are secreted to modulate the healing process within wounds. The obedema percent of 250 ppm AgNPs was nearly the same as appeared in the case of standard drug (indomethacin). The safety of AgNPs on subsequent experiments should be kept at or below 10 μg/mL. The antimicrobial wound dressing of AgNPs treated cotton fabrics is proposed to have promising potential in smart textiles, medical purposes as well as in various biological fields. |