Size Controlled Fabrication of Starch Acetate Nanoparticles and Assessment of their Potential Applications as Hydrophobic Drug Carriers
| dc.contributor.advisor | Prof.Gebre-Mariam, Tsige | |
| dc.contributor.advisor | Dr. Neubert, Reinhard HH(Prof.) | |
| dc.contributor.author | Teka, Getahun Paulos(PhD) | |
| dc.date.accessioned | 2020-05-27T08:10:52Z | |
| dc.date.accessioned | 2023-11-06T08:09:06Z | |
| dc.date.available | 2020-05-27T08:10:52Z | |
| dc.date.available | 2023-11-06T08:09:06Z | |
| dc.date.issued | 2019-03 | |
| dc.description.abstract | Size Controlled Fabrication of Starch Acetate Nanoparticles and Assessment of their Potential Applications as Hydrophobic Drug Carriers Getahun Paulos, Addis Ababa University, 2019 Over the past few decades, there has been considerable interest in developing biodegradable polymer-based nanoparticles (NPs) to effectively deliver a drug to a target site. Polymeric materials used for preparing NPs for drug delivery must be biocompatible and preferably biodegradable. Starch has been a focus of increasing attention in recent years for the design and engineering of novel nanoparticulate drug delivery systems due to its desirable attributes including plentiful availability, renewability, biocompatibility, biodegradability, nontoxicity and ease of modification. The objectives of this study were to fabricate NPs from acetylated starches having particle size less than 200 nm with minimum polydispersity index (PDI); to investigate if the origin of starch has effect on the particle size and PDI of starch acetate (SA) NPs; to investigate the potential applications of SA as nano drug carrier with respect to drug loading (DL) capacity, encapsulation efficiency (EE) and release profile; and to determine the influence of solubility and partition coefficient of different drugs on the characterstics of starch-based NPs. To meet these objectives, acetylated starch was first synthesized by reacting native (cassava, dioscorea, enset and maize) starches with acetic anhydride (AA) in the presence of sodium hydroxide as a catalyst. Starch acetate nanoparticles (SANPs) were then fabricated via spontaneous emulsification solvent evaporation method (using, chloroform, dichloromethane or ethyl acetate; surfactants - Pluronic® F68, Pluronic® F127, Polyvinyl Alcohol (PVA) or Tween® 80) and nanoprecipitation method (using Pluronic® F127). A systematic investigation of independent variables revealed that solvent type, surfactant type and concentration, and homogenization speed and time have significant influence on the size and PDI of SANPs. Hence, response surface methodology (RSM) based on central composite design (CCD) was employed to fabricate the desired SANPs (particle size less than 200 nm and PDI < 0.2) under optimized condition. According to RSM based on CCD, the predicted optimum responses (particle size and PDI) of SANPs of cassava starch were found to be 94.48 1.622 nm and 0.107 0.024, respectively, whereas, the experimentally determined responses were found to be 96.37 nm 1.208 nm and 0.131 0.021, respectively using emulsification solvent evaporation method. The predicted optimum responses and experimentally determined responses obtained under optimal fabrication conditions of independent variables (consisting of ethyl acetate, 1.51% of Pluronic® F127, homogenization speed of~15,000 rpm and homogenization time of ~16 min) were therefore found to be in reasonable agreement. Hence, judicious selection of solvent system and surfactant as well as optimizing formulation and process variables is crucial in order to fabricate the desired NPs. Based on the optimized conditions for fabrication of NPs, comparative study was conducted to determine if the origin of starch has effect on particle size and PDI of SANPs. The size and PDI of SANPs fabricated by emulsification solvent evaporation method were found to be 94.48 nm 1.622, 0.107 0.024 (cassava), 90.27 nm 4.257, 0.133 0.031 (dioscorea), 98.74 nm 2.975, 0.176 0.011 (enset) and 104.61nm 2.766, 0.076 0.001 (maize), respectively. SANPs fabricated by nanoprecipitation method were found to be 211.52 nm 7.42, 0.356 0.016 (cassava), 201.74 nm 9.53, 0.243 0.051 (dioscorea), 207.63 nm 5.75, 0.283 0.035 (enset) and 216.691nm 6.80, 0.203 0.027 (maize), respectively. The size and PDI of cassava SANPs fabricated either by emulsification solvent evaporation or by nanoprecipitation methods were significantly different from those NPs obtained from dioscorea, enset or maize SAs (p ˂ 0.05). Similar differences were also observed among the NPs of dioscorea, enset and maize SAs, indicating the origin of starch has significant effect on fabrication of SANPs. Based on ICH guideline, SANPs stored for 3 months at different storage conditions (5°C ± 3°C, 25°C ± 2°C/60% ± 5% RH and 40°C ± 2°C/75% ± 5% RH) remained stable. SANPs prepared from various SAs with different degrees of substitution (DS) were loaded with ibuprofen or oat ceramides (CERs) and their properties, namely, size, PDI, DL, EE, release profiles were studied. Like unloaded SANPs, ibuprofen or oat CERs loaded SANPs were also fabricated with desired particle size (< 200 nm) and PDI (< 0.2). The DL and EE of SANPs increased with an increase in the DS. The average DL of ibuprofen and oat CERs loaded SANPs increased from 9.3 to 26.6% and 8.8 to 21.2%, respectively as DS of SAs increased from low (0.91) to high (2.74). Similarly EEs of ibuprofen and oat CERs increased from 44.7 to 78.3% and 2.2 to 85.2%, respectively. In vitro drug release of ibuprofen was sustained over 8 h of study period. Drug release profile of SANPs followed Higuchi Model. In vitro a comparative artificial membrane penetration study, the release and penetration of oat CERs from microemulsion (ME) was higher than from SANPs. Over 90% of oat CERs incorporated in ME, and 59-63% oat CERs in the SANPs were released and penetrated into multilayer membrane system after 60 min. Thus, compared to ME, SANPs retarded the release of oat CERs into the artificial membrane. Hence, this study provides insight into the potential applications of SANPs as sustained release nano drug carrier. Finally, the effects of solubility and partition coefficient of different model drugs based on Biopharmaceutics Classification System (BCS) Class II (ibuprofen), BCS Class III (acyclovir) and BCS Class IV (furosemide) on DL, EE and release profile of SANPs were investigated. The results showed that the DL and EE of ibuprofen and furosemide-loaded SANPs increased consistently with an increase in the DS of SA. On the contrary, DL and EE of acyclovir-loaded NPs decreased as DS of SA increased. Due to their poor solubility and high partition coefficient, the EEs of ibuprofen (77.9%) and furosemide (80.5%) in SANPs fabricated from SA with high DS were much greater than that of acyclovir (50.9%). Furthermore, as DS of SA increased, the cumulative release of ibuprofen from SANPs was retarded whereas the release of acyclovir was enhanced. On the other hand, furosemide, the most lipophilic drug of all, exhibited the lowest extent of release over the study period. Hence, along with the hydrophobic nature of SA, the DL, EE and drug release profile from SANPs were dependent on the solubility and partition coefficient of the incorporated drug molecule. In conclusion, the favourable particle size, PDI, DL and EE with sustained drug release profile suggest that SANPs could be regarded as promising carriers in nano drug delivery systems. | en_US |
| dc.identifier.uri | http://etd.aau.edu.et/handle/123456789/21329 | |
| dc.language.iso | en_US | en_US |
| dc.publisher | Addis Abeba University | en_US |
| dc.subject | Acetylated starch, Central composite design, Drug loading capacity, Emulsification solvent evaporation, Encapsulation efficiency, Nanoprecipitation, Particle size, Polydispersity index, Release profile, Response surface methodology, Starch acetate nanoparticles | en_US |
| dc.title | Size Controlled Fabrication of Starch Acetate Nanoparticles and Assessment of their Potential Applications as Hydrophobic Drug Carriers | en_US |
| dc.type | Thesis | en_US |