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dc.contributor.authorGAUTAM, MEENAKSHI-
dc.date.accessioned2021-08-12T07:13:04Z-
dc.date.available2021-08-12T07:13:04Z-
dc.date.issued2020-07-
dc.identifier.urihttp://dspace.dtu.ac.in:8080/jspui/handle/repository/18443-
dc.description.abstractAmong the various routes of drug administration, oral administration is the most widely used and common delivery system associated with the gastrointestinal (GI) tract. It is easily accessible, self-administered and having high potential for the reduction of side effects of the drug dosages. It also provides several challenges for the researchers; for instance, variation in pH of the GI tract, to protect the drug from the harsh environment in the stomach, intestine motility and finally, mucus barrier. To overcome these obstacles, it is necessary to design a new strategy with the colonspecific delivery system. A colon is the ideal delivery site where a drug can be protected from the attack of numerous proteases. CaCO3 nanoparticles due to their properties such as biodegradability and biocompatibility have significant priority in the biomedical field. CaCO3 nanoparticles are highly porous in nature and show high drug loading capacity owing to their high surface area to volume ratio. They can be easily synthesized and are cost-effective. Moreover, surface modification is easily possible with the CaCO3 nanoparticles by which these nanoparticles have been considered as a great carrier in the targeted delivery of drug. CaCO3 nanoparticles are naturally present in the human body and show stability in the biological matrix. They have pH dependent solubility, and nontoxic material approved by FDA. Food grade oral delivery vehicles for the targeted delivery of nutrients are currently fabricated by adapting pharmaceutical approaches to promote human health. Food grade delivery systems contain nutritional value along with appreciable functionality. Abstract These may be protein, carbohydrate and lipid-based systems. Food grade oral delivery systems have been reported as appropriate and safer vehicles as approved by the FDA. Moreover, these food grade approaches are used as a matrix for the synthesis of nanoparticles since they have ability to control the size of the nanoparticles and also enhance the functionality of the delivery system. They are cost-effective approaches to the prevention and treatment of various diseases. Interestingly, pectin a naturally occurring edible polymer has been used as a drug carrier in the biomedical field. Pectin shows an excellent gelling property therefore used in the formation of hydrogel that can be used for oral delivery. Besides, pectin exhibited various properties such as pH sensitive, biodegradability, mucoadhesive. Hence, Pectin based drug carriers are considered as a colon specific delivery system as they exhibit prolonged retention and completely degraded by the bacteria present in the colon. In this thesis, considering the huge consequences of CaCO3 as well as pectin for targeted oral delivery, synthesis and characterization of CaCO3 nanoparticles was focused. Subsequently, to avoid the aggregation of the nanoparticles, pectin based hydrogel was introduced and an attempt has been made for in-situ mineralized CaCO3 particles in pectin based hydrogel matrix. This thesis has been summarized in five chapters. Chapter 1 discusses a brief introduction of oral drug delivery, attributes of the colon specific drug vehicles, and CaCO3 nanoparticles along with their biomedical applications. A brief introduction of edible hydrogel and the importance of pectin, zein and PEG polymer are also mentioned. Abstract Chapter 2 provides the details of instruments used for the characterization of the material and their working principle are also discussed. Chapter 3 involves the synthesis of CaCO3 nanoparticles using gelatin as a template through a novel bio-inspired method for the sequential delivery of vitamin D and amoxicillin. The synthesized CaCO3 nanoparticles were characterized using Transmission electron microscopy (TEM), X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Thermogravimetric analysis (TGA) and Brunauer-Emmett-Teller (BET). XRD and TEM confirmed nanocrystalline nature of CaCO3 in size range of 10-15 nm. Further, CaCO3 nanoparticles encapsulated with vitamin D, coated with zein and finally loaded with amoxicillin as a model drug. The release study of vitamin D and amoxicillin was performed in the simulated gastric fluid (SGF) (pH 1.2) and simulated intestinal fluid (SIF) (pH 6.8) and (pH 7.4) at 37 °C temperature. The encapsulation of hydrophobic vitamin D in CaCO3 nanoparticles with an external zein coating approach enhances their controlled and sustained release property at the target site. The role of gelatin molecule in the synthesis of nano-sized CaCO3 was demonstrated using CD spectroscopy. MTT assay was performed on zein coated CaCO3 nanoparticles at varying concentrations on kidney (HEK) and liver (Hep G2) cell lines after 24 hours exposure to ensure its biocompatibility. In chapter 4, Ca2+ with vitamin D / Fe2+ with vitamin C were entrapped in edible pectin/PEG polymer blend matrix to obtain hydrogels namely PPCaD and PPFeC. Thermogravimetric analysis (TGA) and Fourier transform infrared spectroscopy (FTIR) analysis of pectin based hydrogels confirmed the existence of metal ion Abstract content in the hydrogel matrix and their corresponding interaction with the pectin matrix through electrostatic and hydrogen bonding. Rheological measurements revealed a higher elastic nature of PPCaD compared to PPFeC and were in good agreement with the swelling studies. In-vitro release studies concluded that the lowest release of metal ion and vitamin from the corresponding hydrogel samples in simulated gastric fluid (SGF) was observed at pH 1.2 for 3 h. It indicated that protection of nutrients from the gastric environment was conferred by the hydrogels. The release studies carried out in the next 3 h in simulated intestinal fluid (SIF) at pH 6.8 indicated not only the highest swelling of the hydrogel samples but also the highest co-release of nutrients at the intestinal site. In Chapter 5 CaCO3 microparticles were in-situ mineralized in pectin/poly(ethylene glycol) (PEG) hydrogel blend to protect and release protein drug at the colon site. Further, bovine serum albumin (BSA) as a model drug was loaded during the fabrication of pectin/PEG blend containing in-situ mineralized CaCO3 particles. The interaction of loaded BSA with CaCO3 by physical forces was evidenced by FTIR analysis. BSA could also be visualized around the mineralized CaCO3 by TEM throughout the hydrogel matrix. Rheological studies on the oral delivery vehicle revealed dynamic nature of the hydrogel, an essential property required for drug carriers for its interaction with the target site. In-vitro swelling and protein release studies of pectin based hydrogel indicated the potentiality of the drug carrier in releasing protein at the colon site. The conformational stability of the released BSA from the hydrogel blend (PPCB) was confirmed by SDS-PAGE and CD spectropolarimetry.en_US
dc.language.isoenen_US
dc.publisherDELHI TECHNOLOGICAL UNIVERSITYen_US
dc.relation.ispartofseriesTD - 5246;-
dc.subjectGASTROINTESTINAL (GI)en_US
dc.subjectCACO3en_US
dc.subjectFDAen_US
dc.subjectTRANSMISSION ELECTRON MICROSCOPY (TEM)en_US
dc.subjectBRUNAUER-EMMETT-TELLER (BET)en_US
dc.subjectXRD AND TEMen_US
dc.titleTEMPLATE ASSISTED CALCIUM BASED DRUG CARRIERS FOR EFFICIENT ORAL DELIVERY APPLICATIONSen_US
dc.typeThesisen_US
Appears in Collections:Ph.D. Applied Chemistry

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