Biodegradable polymeric particles encapsulating an active agent, pharmaceutical compositions and uses thereof

A pharmaceutical composition comprising:

• a) a biodegradable polymeric composite particle comprising:
• at least one active agent encapsulated in a hollow or aqueous core by a shell comprising a mixture of from about 50 wt-% to about 99 wt-% of a first polymer, wherein the first polymer is a hydrophobic polymer, and from about 1 wt-% to about 50 wt-% of a second polymer comprising chitosan, alginate, or collagen, wherein the first and second polymer are distributed in a gradient from the core to a surface of the composite with the first polymer having a higher concentration at the core and the second polymer having a higher concentration at the surface of the composite;
• wherein the at least one active agent is released as a delayed dose after a period of at least 7 days to 6 months;
• and
• b) at least one additional active agent free from and not encapsulated by the polymeric composite particle;
• wherein the at least one additional active agent provides an initial burst dose and the polymeric composite particle provides the delayed dose of the at least one active agent,
• wherein the at least one active agent encapsulated in the core and the at least one additional active agent free from the particle is the same active agent or different active agents;
• and wherein the polymeric composite particle has a particle size of from about 10 nanometers to less than 900 nanometers.