Design of novel mesoporous nanocapsules and their therapeutic efficiencies as a drug delivery carrier and to enhance the immunological responses

Abstract

With passing time medical field has been improving rapidly, because of incessant new inventions by researches in this particular field. Presently, nanotechnology has strengthened its root in all trajectory of the biomedical field with a focused persistence for human healthcare and together it can be termed as nanobiotechnology. Consequently, it has shown potential in drug formation, preventing and curing any disease, cancer therapy, drug delivery system, tissue engineering, MRI contrast agent and many more. Biocompatible and biodegradable nanomaterials play a noteworthy part in this trait. Currently, porous nanomaterials have enlightened the tremendous possibilities in the applied field of biotechnology by offering void space to encapsulate or entrapped particles in it like a nanocargo followed by delivery those encapsulated particles in the site of interest by a sustained controlled release and after unloading that nanocargo in physiological condition without leaving any side effects. Encapsulated particles can be drugs, biomolecules, gene, protein and a range of therapeutics. From a healthcare point of view, these nanomaterials with characteristic porous structures can decrease the doses of drugs thereby reducing toxicity occurred due to the therapeutics and also increase the possibility of bioavailability of therapeutics. Then the challenge occurred with the size of the nanocarrier along with the size of the pores. Therefore, synthesis of nanomaterials with all required characteristics as a carrier has become vital. However, polymer nanostructures are getting additional highlights because of their biocompatible and biodegradable nature but few metal NPs like silica, zinc oxide, quantum dots, titanium dioxide, iron oxide, etc. have also proved their efficiency as nanodrugcarrier with small size, rigid arrangements, long shelf life as well as interact with cellular biomolecules thereby facilitates admittance into the cell. This dissertation comprises a detail synthesis approach of three types of polymeric and inorganic nanomaterials with varying sizes, followed by a complete systematic characterization for the biomedical application. Conventional sole gel techniques, chemical synthesis by using nanotemplates and surfactant free sonochemical technique have been followed for the synthesis of nanomaterials with different characteristics such as core-shell, hollow porous and mesoporous. Three different therapeutic fields have been included in this work for theapplication purpose of synthesized porous structured nanomaterials and the fields are Malaria, Immunology and Cancer Therapy. Malaria is becoming a big threat in human by becoming resistant to almost all available malaria medications and thereby causing about 216 million cases in 91 countries annually with 445000 deaths according to WHO. There instant proper up gradation in the Malaria treatment is becoming a very urgent issue. The first part of this dissertation includes the development of a coreshell nanostructure where different sizes of SiO2 NPs synthesized by sole gel technique have been used as core and PCL polymer formed the outer shell layer. Later the templates SiO2 NPs have been etching out to create a new PCL NC with hollow porous morphological characteristics. This novel amorphous hollow porous PCL NCs are biocompatible biodegradable and have a great encapsulation efficiency while loaded with antimalarial drugs Dihydroartemisinin and Chloroquine and Sulfadoxine. Their antimalarial activities have been studied with Malaria causing P. falciparum parasitic cell culture where these NCs have efficiently inhibit the growth of the parasite-infected RBCs compared to free drugs. These NCs are unique because they can be tuned as a “time temperature clock” module i.e., they can be tuned with predetermined drug dosses obligatory for the Malaria treatment with an increase of body temperature due to the infection. This nanodrugcarrier has the potential to control the release of confined drugs from it as soon as the temperature arises gradually reduces the release of drug with a gradual decrease in the temperature to normal. Therefore, this unique polymer based NCs can be used as nanodrug carrier for eradicating P. falciparum growth efficiently. In the field of nanobiotechnology, nanostructures based on metal have received importance recently for the formation of vaccines. Moreover, nanostructured with porous morphology is an excellent candidate in that regard. The second part of this dissertation included designing of nanostructured ZnO with mesoporous morphology by surfactantfree sonochemical method. This unique stable mesoporous ZnO NCs showed outstanding loading efficiency by encapsulating protein Ova. These protein loaded metal oxide NCs have immunized in mice model to investigate the enrichment of immunological responses. Ova has worked as an antigen in this regard for improvement in CD8+ and CD4+ T-cell effector responses. Antigen-specific IgG levels and IgG2a or IgG2b levels in serum has also increased when lymph node and serum of Ova loaded mZnO immunized mice have studied. The role of mesoporous ZnO NCs in enriching the immune response makes it as a good promoter to design nanovaccines in the field of medicine to prohibit various ailments. Later these mesoporous nanocarriers have been used to encapsulate antimalarial drugs Dihydroartemisinin,Chloroquine and Sulfadoxine and anticancer drugs DOX and paclitaxel and a systematic sustained controlled drug release pattern can be observed in each drug conjugate nanoformulations. The cellular level interaction of drugs loaded mZnO NCs with cancer cell line K562 have been studied where these NCs entirely deformed the malignant cell structures and thereby proved their efficiency as a drug carrier. With the development of biomedical field, the therapeutic field Cancer has also developed. A part of credit can be claimed by the involvement of nanotechnology in this particular medical field with new innovative researches to avoid complications related to the treatment. The third part of this dissertation includes engineering of a core-shell nanostructure with mesoporous ZnO NCs as a template and polymer PCL as coating layer where 2-3 templates were coated by a polymeric shell. Later these temples were etched out by leaving pores in the polymer nanostructures. This amorphous NC is biocompatible and biodegradable in nature with a great drug encapsulation efficiency. Biocompatibility of this NCs with the templates as well as without templates were investigated with two different breast cancer cell lines MCF 7 and MDA-MB-231 respectively. The drug Paclitaxel has been used to load inside the NCs pores and cell inhibition assay have been conducted by using MCF 7 and MDA-MB-231 where drug loaded with NCs performed more malignant cell inhibition property compared to free Paclitaxel drug. Moreover, this nanocarrier showed lower IC50 compared to free drug. Thus these polymer-based nanodrug carriers can decrease the toxic drug doses thereby reducing side effects and also can increase the bioavailability of therapeutics.