One of the easiest ways to think about this is how lonely it is at the top, in this case how lonely it is for Macbeth and Lady Macbeth. Before their treachery of killing for and taking the throne, they were surrounded by fame and glory. Macbeth was renowned for his bravery and capability on the battlefield; he was recognized by the king for this greatness; he was given lands and titles; he had a best friend in Banquo. Once they commit treason, all this is gone. Even though they are King and Queen and at the top of the hierarchy, they are increasing alone, isolated, only surrounded by murderers or servants who will do their bidding. The majority of the kingdom is behind the rightful king, Malcolm and his revolution versus the tyrant and his wife.
So in your essay, discuss what Macbeth and Lady Macbeth have done to increasingly isolate themselves and how this isolation affects their journey, the course of their lives, which means you have to get at their deaths, how and why they die.
You may also explore other characters who isolate themselves: Malcolm and Donalbain who flee Scotland after their father's murder; the witches who isolate themselves from human interaction and the public and only unveil themselves when they want to; Banquo and Fleance who attempt to isolate themselves. Be sure to explain why they are isolating themselves and what effect that has on their situations and / or their lives.