Formulations of biologics for intravesical instillation
Pharmaceutical formulations comprising a clostridial derivative and a permeabilizing agent for intravesical instillation are disclosed.
1. A pharmaceutical composition comprising a therapeutically effective amount of a clostridial derivative and at least one permeabilizing agent, wherein:
the at least one permeabilizing agent is present in an amount effective to substantially and reversibly increase the permeability of the bladder wall to the clostridial derivative;
the clostridial derivative is a botulinum toxin;
the at least one permeabilizing agent comprises a surfactant and a mucoadhesive;
the surfactant is present in an amount of about 0.1% (w/v);
the mucoadhesive comprises chitosan; and
the surfactant comprises octoxynol-9.
2. The pharmaceutical composition of claim 1 , wherein the mucoadhesive is present in an amount ranging from about 0.01% to about 5% (w/v).
3. The pharmaceutical composition of claim 1 , wherein the mucoadhesive is present in an amount of about 1% (w/v).
4. The pharmaceutical composition of claim 1 , wherein the clostridial derivative is a botulinum toxin type A.
5. The pharmaceutical composition of claim 1 , wherein the surfactant is present in an amount of 0.1% (w/v).
6. A method of treating a neurogenic bladder dysfunction in a patient in need thereof, comprising intravesically instilling to the bladder wall of the patient a pharmaceutical composition, wherein:
the pharmaceutical composition comprises a therapeutically effective amount of a clostridial derivative and at least one permeabilizing agent present in an amount effective to substantially increase the permeability of the bladder wall to the botulinum neurotoxin at a therapeutically effective rate;
the clostridial derivative is a botulinum toxin;
the at least one permeabilizing agent comprises a surfactant and a mucoadhesive;
the surfactant is present in an amount of about 0.1% (w/v);
the mucoadhesive comprises chitosan; and
the surfactant comprises octoxynol-9.
7. A pharmaceutical composition comprising a therapeutically effective amount of a clostridial derivative and at least one permeabilizing agent, wherein:
the at least one permeabilizing agent is present in an amount of 0.005-10% (w/v) to substantially and reversibly increase the permeability of the bladder wall to the clostridial derivative;
the clostridial derivative is a botulinum toxin;
the at least one permeabilizing agent comprises a surfactant and a mucoadhesive;
the surfactant is octoxynol-9; and
the mucoadhesive is chitosan.
8. The composition of claim 7 , wherein the surfactant is present at about 0.1% (w/v) and the mucoadhesive is present at about 1% (w/v).
9. A method of treating a neurogenic bladder dysfunction in a patient in need thereof, comprising intravesically instilling to the bladder wall of the patient a pharmaceutical composition of claim 7 .