Surfactant-polymer nanoparticles: a novel platform for sustained and enhanced cellular delivery of water-soluble molecules.
OBJECTIVE
Nanoparticles, drug carriers in the sub-micron size range, can enhance the therapeutic efficacy of encapsulated drug by increasing and sustaining the delivery of the drug inside the cell. However, the use of nanoparticles for small molecular weight, water-soluble drugs has been limited by poor drug encapsulation efficiency and rapid release of the encapsulated drug. Here we report enhanced cellular delivery of water-soluble molecules using novel AerosolOT (AOT)-alginate nanoparticles recently developed in our laboratory.


METHODS
AOT-alginate nanoparticles were formulated using emulsion-crosslinking technology. Rhodamine and doxorubicin were used as model water-soluble molecules. Kinetics and mechanism of nanoparticle-mediated cellular drug delivery and therapeutic efficacy of nanoparticle-encapsulated doxorubicin were evaluated in two model breast cancer cell lines.


RESULTS
AOT-alginate nanoparticles demonstrated sustained release of doxorubicin over a 15-day period in vitro. Cell culture studies indicated that nanoparticles enhanced the cellular delivery of rhodamine by about two-tenfold compared to drug in solution. Nanoparticle uptake into cells was dose-, time- and energy-dependent. Treatment with nanoparticles resulted in significantly higher cellular retention of drug than treatment with drug in solution. Cytotoxicity studies demonstrated that doxorubicin in nanoparticles resulted in significantly higher and more sustained cytotoxicity than drug in solution.


CONCLUSIONS
AOT-alginate nanoparticles significantly enhance the cellular delivery of basic, water-soluble drugs. This translates into enhanced therapeutic efficacy for drugs like doxorubicin that have intracellular site of action. Based on these results, AOT-alginate nanoparticles appear to be suitable carriers for enhanced and sustained cellular delivery of basic, water-soluble drugs.
Chavanpatil
Mahesh D
MD
Department of Pharmaceutical Sciences, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA.
Khdair
Ayman
A
Panyam
Jayanth
J
D000464:Alginates / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D004317:Doxorubicin / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D004337:Drug Carriers; D004339:Drug Compounding; D005089:Exocytosis; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008970:Molecular Weight; D053758:Nanoparticles; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D012235:Rhodamines / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013501:Surface-Active Agents / Q000737:chemistry*; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors; D014867:Water / Q000737:chemistry
D000464:Alginates; D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D006603:Hexuronic Acids; D011108:Polymers; D012235:Rhodamines; D013501:Surface-Active Agents; D014867:Water; D004143:Dioctyl Sulfosuccinic Acid; D004317:Doxorubicin; D020723:Glucuronic Acid