| Popis: |
The historical precedence for employing bacteria to target cancer stretches long back some 300 years. Despite of the advancements in chemotherapy, problems such as metastasis and tumour resistance to chemotherapy and radiotherapy have limited the scope of therapeutic effects of existing clinical treatments. The microenvironment of solid tumours provides an ideal environment for growth of facultative and strictly anaerobic bacteria. These bacteria can colonize such environments leading to tumour regression. Such investigations have given the concept of bacteriolytic therapy, in which live bacteria could be employed for the targeted delivery into tumours leading to its suppression. With this concept in mind it was decided to explore the above idea by using probiotic bacterium (Lactobacillus casei), which is considered to be non-pathogenic and also provides health benefits to the host. In order to minimize dispersion of the bacteria throughout the host and to facilitate its delivery into tumours, some kind of containment was desirable. To test this kind of approach it was decided to exploit immobilisation technology to microencapsulate live bacteria for later injection into tumour sites. To date no such approach has been employed to develop such a microencapsulation system that could be utilized as a delivery vehicle for live bacteria to deliver it through a hypodermic needle directly into tumours. In order to pursue the above objective, the microencapsulation method was also characterised with respect to stability and viability of the L.casei. Microencapsulated preparations of Lactobacillus casei NCDO 161 were developed and demonstrated that the culture supernatant of microencapsulated preparation inhibited growth of tumour cells (in vitro). Further investigation of a variety of bacterial preparations on tumour growth (in vivo) following intra-tumoural injection demonstrated that the live microencapsulated preparation had severe inhibitory effect on tumour growth when compared with non-encapsulated live and encapsulated heat killed preparations. Histological studies were performed to demonstrate the presence of live bacteria in tumours at early stages and to study the effects of the bacteria on tumour architecture during the treatment. |
