Combination chemotherapeutic dry powder aerosols via controlled nanoparticle agglomeration.
OBJECTIVE
To develop an aerosol system for efficient local lung delivery of chemotherapeutics where nanotechnology holds tremendous potential for developing more valuable cancer therapies. Concurrently, aerosolized chemotherapy is generating interest as a means to treat certain types of lung cancer more effectively with less systemic exposure to the compound.


METHODS
Nanoparticles of the potent anticancer drug, paclitaxel, were controllably assembled to form low density microparticles directly after preparation of the nanoparticle suspension. The amino acid, L-leucine, was used as a colloid destabilizer to drive the assembly of paclitaxel nanoparticles. A combination chemotherapy aerosol was formed by assembling the paclitaxel nanoparticles in the presence of cisplatin in solution.


RESULTS
Freeze-dried powders of the combination chemotherapy possessed desirable aerodynamic properties for inhalation. In addition, the dissolution rates of dried nanoparticle agglomerate formulations (approximately 60% to 66% after 8 h) were significantly faster than that of micronized paclitaxel powder as received (approximately 18% after 8 h). Interestingly, the presence of the water soluble cisplatin accelerated the dissolution of paclitaxel.


CONCLUSIONS
Nanoparticle agglomerates of paclitaxel alone or in combination with cisplatin may serve as effective chemotherapeutic dry powder aerosols to enable regional treatment of certain lung cancers.
Department of Pharmaceutical Chemistry, The University of Kansas, Lawrence, Kansas 66047, USA.
Nashwa
N
El-Gendy
Cory
C
Berkland
D000280:Administration, Inhalation; D000336:Aerosols / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D004359:Drug Therapy, Combination; D005612:Freeze Drying; D006801:Humans; D007930:Leucine / Q000737:chemistry; D008168:Lung / Q000166:cytology; D053758:Nanoparticles / Q000737:chemistry* / Q000633:toxicity / Q000648:ultrastructure; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry / Q000633:toxicity; D010316:Particle Size; D011208:Powders / Q000737:chemistry; D012995:Solubility; D044366:Transition Temperature
D000336:Aerosols; D000970:Antineoplastic Agents; D011208:Powders; D007930:Leucine; D017239:Paclitaxel; D002945:Cisplatin