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sexta-feira, 6 de julho de 2012

First trial tests targeted Nanoparticles in patients

[By Deborah McBride, RN, MSN, CPON®, Contributor]
The first trial to test a tar­geted nanopar­ti­cle capa­ble of con­trol­ling a drug’s release is now under way in humans. The tiny par­ti­cles were designed to deliver the chemother­apy drug doc­etaxel, used to treat lung, prostate, and breast can­cers, among others.
Using nanopar­ti­cles allows researchers to deliver a higher dose of can­cer drugs directly to tumors but reduces tox­i­c­ity to patients. In mouse mod­els, the amount of doc­etaxel deliv­ered to tumors was seven times higher in mice infused with doc­etaxel nanopar­ti­cles com­pared with tra­di­tional doc­etaxel. In addi­tion, the researchers saw a greater reduc­tion in tumor mass in mice that received doc­etaxel nanopar­ti­cles. Side effects were no worse with the nanopar­ti­cles than with the tra­di­tional, unpack­aged chemother­apy drug.
In other ani­mal stud­ies, researchers found that doc­etaxel nanopar­ti­cles cir­cu­lated in the blood­stream much longer and the drug remained safely encap­su­lated inside the nanopar­ti­cle shell while in the blood­stream. Also, doc­etaxel nanopar­ti­cles did not accu­mu­late in the liver, an unwanted occur­rence that is almost always seen with other nanoparticles.
Based on those pre­vi­ous stud­ies, researchers started a phase I clin­i­cal trial in peo­ple with solid tumors that have not responded to a range of chemother­a­pies to deter­mine the max­i­mum tol­er­ated dose of a tar­geted nanopar­ti­cle called BIND-​​014. Although the trial is ongo­ing, early data from the first 17 patients show that the nanopar­ti­cle exhibits anti­tu­mor activ­ity and is gen­er­ally well tolerated.

Researchers found that in the 48 hours after treat­ment, doc­etaxel con­cen­tra­tion in the patients’ blood was 100 times higher with the nanopar­ti­cles as com­pared to doc­etaxel admin­is­tered in its con­ven­tional form. The higher blood con­cen­tra­tion resulted in tumor shrink­age in patients, in some cases with doses of BIND-​​014 that cor­re­sponded to as low as 20% of the amount of tra­di­tional doc­etaxel nor­mally given. The nanopar­ti­cles were also effec­tive in can­cers in which doc­etaxel usu­ally has lit­tle activ­ity, such as cer­vi­cal can­cer and can­cer of the bile ducts.
The study’s researchers had to develop a new nanopar­ti­cle design. Pre­vi­ously, researchers had tried to mod­ify a pro­to­type nanoparticle’s char­ac­ter­is­tics by attach­ing mol­e­cules for tumor cell bind­ing. The prob­lem with this process is the lack of repro­ducibil­ity for small changes in design related to batch-​​to-​​batch vari­abil­ity, mean­ing that they could not cre­ate nanopar­ti­cles that dif­fered from each other very nar­rowly to find the right phar­ma­ceu­ti­cal parameters.
To address that prob­lem, researchers cre­ated a library of more than 100 unique nanopar­ti­cles. The nanopar­ti­cles start out as a long string of mol­e­cules, each with dif­fer­ent functions—for exam­ple, hold­ing and releas­ing the chemother­apy drug, hid­ing the nanopar­ti­cle from the immune sys­tem, or bind­ing to tumor cells. Small changes can be made to any of the mol­e­cules in the string before assem­bly, cre­at­ing small vari­a­tions that can be screened for the desired prop­er­ties of a drug-​​delivery vehi­cle. After those prop­er­ties are added to the string, the chemother­apy drug is added to cre­ate a pre­cisely designed nanopar­ti­cle in a highly repro­ducible way.
In the future, it is hoped that nanomed­i­cines like this will lead to more man­age­able and effec­tive chemother­a­pies. In addi­tion, it may be pos­si­ble to revisit drugs that failed in clin­i­cal tri­als in the past because they were too toxic, if nanopar­ti­cles make it pos­si­ble to deliver them in a safer way.
Deborah McBrideContributor Deborah McBride, RN, MSN, CPON®, is a staff nurse IV at the Kaiser Permanente Oakland Medical Center and an assistant professor at Samuel Merritt University in Oakland, CA. Read more articles by Deborah McBride

Fonte: ONS Connect