The development of nanoparticles to improve the delivery of bioactive compounds to the brain via the peroral route

Conventional drug formulations and recently developed drugs often suffer from poor solubility, absorption or both, resulting in poor bioavailability. The development of polymeric NPs is one current delivery method capable of improving the therapeutic efficacy of the drug by altering both the solubility and the absorption from the GIT. The primary aim of this project was the development of NPs capable of encapsulating various compounds with different physicochemical properties. This study chose estradiol, curcumin and amphotericin B (AMB) as the three drugs with which to evaluate whether the loaded T-80 coated NPs were capable of improving the absorption of the selected compound and whether it enhanced the retention time compared to the uncoated NPs. The secondary objective was to determine if coating the NPs with T-80 was able to improve the uptake of the active compound in to the brain versus uncoated NPs. In order to evaluate these objectives, the delivery system was first developed and then an in vivo biodistribution test was carried out using Sprague-Dawley rats. The study developed PLGA NPs using PVA as a stabiliser to entrap the compounds. The NPs were characterised using a Malvern Zetasizer, with AMB NPs in average forming the largest NPs (365.9 nm) and curcumin NPs the smallest (290.3 nm). The zeta potential was seen to decrease significantly when the NPs were coated with T-80 signifying the successful coating of the NPs. The % EE of the compounds varied significantly, with 35.0 ± 2.03, 31.5 ± 1.26, 62.3 ± 4.06, 54.6 ± 1.52, 81.7 ± 5.73, 4.97 ± 3.31, 70.7 ± 8.32 % reported for AMB NC, AMB T-80, curcumin NC, curcumin T-80, estradiol NC, estradiol 4 % T-80 and estradiol 0.5 % T-80 respectively. The main aim was to show that T-80 coating was able to increase the absorption of the NPs in to the various tissues. This was evaluated using a biodistribution study. The results from this study showed no significant increases in the levels of any of the compounds in any of the tissues analysed, and no significant difference in the retention time was observed either. It is likely that the larger size of the AMB NPs is the reason for the poor biodistribution in the AMB study, and for the estradiol and curcumin study, the large number of single batches required to produce an adequate dose could have resulted in poor overall entrapment efficiency or agglomeration of the NPs which again would affect the results. Overall, the study did not prove either the primary or the secondary objective, and the time spent attempting to coat NPs with 4 % T-80 proved detrimental to the overall scope of the project.

Name dc:type.qualificationname

mres

Level dc:type.qualificationlevel

masters-pg

Grantor dc:publisher.institution

University of Strathclyde

Year dc:date.issued

2012

Author dc:creator

• Sullivan, Martin John George

DOI

10.48730/5bbb-4t26

Identifier

T13628

OAI identifier oai:identifier

oai:strathclyde:wp988j80x