Microneedles unlock curcumin’s therapeutic potential

While turmeric root has been used medicinally all through the world for hundreds of years, science has discovered that its major chemical part, curcumin, breaks down within the physique earlier than its final advantages may be achieved. An thrilling collaboration amongst Carnegie Mellon University researchers Sai Yerneni, Phil Campbell, Burak Ozdoganlar, and Ezgi Yalcintas has created an strategy to uniquely allow using curcumin as a strong therapeutic.

Curcumin is an anti-cancerous, anti-inflammatory, anti-oxidant, and anti-bacterial polyphenol present in turmeric. However, its remoted, pure type shouldn’t be steady attributable to its speedy degradation inside and clearance from the physique. This represents one of many largest obstacles to its translation as a sensible therapeutic. It additionally serves as motivation for researchers to discover encapsulation methods to guard the curcumin contained in the human physique.

One such encapsulation strategy is to include curcumin into exosomes. Exosomes are nanometric extracellular vesicles that the human physique makes use of for cell-to-cell communication by shifting proteins, lipids, nucleic acids, and metabolites. By inserting curcumin in exosomes, the chemical is steady sufficient to journey all through the physique and obtain its therapeutic impact. Although different researchers have tried to make use of exosomes to ship curcumin, the advance in curcumin’s stability was inadequate for its use as a therapeutic.

Albumin, a pure stabilizer protein that happens within the human physique, can deal with this problem. Yerneni, a postdoctoral researcher in chemical engineering, and Campbell, a analysis professor of biomedical engineering, have developed a hybrid strategy to leverage the distinctive properties of each exosomes and albumin. They engineered an exosome-albumin hybrid system to ship therapeutics, together with curcumin.

“Prior attempts to load curcumin into various lipid membrane-bound nanoparticles suffered from the curcumin either being unreliably loaded or subject to short retention times, whereas the inclusion of albumin binds to the curcumin keeping it in the lumen of the exosome, protected from degradation,” stated Campbell.

Although albumin-curcumin affiliation and exosome encapsulation might present a steady drug supply system, focused supply to desired tissues or organs stay one other problem. When injected into the blood, a lot of the exosomes are likely to accumulate within the liver somewhat than reaching the focused organ or tissue. To this finish, a gorgeous strategy is to ship the curcumin-albumin-containing exosomes utilizing microneedle array patches for pores and skin focused purposes.

Microneedle arrays (MNA) include tens or lots of of needles, every as skinny as a human hair and invisible to the bare eye. Through a producing and utility course of first, these micro-scale needles are organized in an array format on a patch smaller than a penny. Dissolvable microneedles are shaped by mixing the drug—exosomes on this case—with a kind of sugar and solidifying them into their form.

When inserted into tissue, the needles dissolve away and ship the drug in a focused and exact method. Due to their small dimension, microneedles don’t trigger tissue harm. As such, they can be utilized as a pain-free approach to ship therapeutics into or via the pores and skin, enhancing affected person compliance and focused supply. Notably, the microneedle patches may be administered by the sufferers themselves with none specialised gear or coaching.

The researchers discovered one other main benefit to utilizing MNAs. When the exosome-fortified curcumin compounds have been included into MNAs, the workforce discovered that the soundness of those compounds at room temperature elevated dramatically. The system may very well be saved for as much as a 12 months with no need chilly storage.

“This is big because of one of the major drawbacks of current vaccines are the logistics of transportation requiring cold storage,” Yerneni stated.

He defined that this particularly disadvantages poorer nations that can’t facilitate lengthy chilly storage provide chains. Yerneni is optimistic that this expertise can overcome these hurdles.

Fabrication and administration of CA-EV-loaded MNAs

(A) Fabrication of EV-loaded microneedle arrays. (Aa) Micromilling of master molds. (Ab) Elastomer molding of the production molds. (Ac) Spin-casting to localize EVs at the tip portions of the obelisk microneedles and fabricate tip-loaded dissolvable MNAs. (B) Characterization of EV-loaded MNAs (Aa-Ad) Optical microscope and (Ae, Af) scanning electron microscopy images of obelisk-shaped dMNAs prepared with tip-loaded EVs. The red color is from 10 µg PKH26-labeled EVs loaded per MNA. (C) Optical microscope and scanning electron microscopy images of EV-loaded dMNAs (a,b) pre- and (c,d) 5 min post-application on ex vivo rat skin, respectively.

A collaborative journey

Yerneni and Campbell had not wanted to go far to discover a collaborator for delivering exosomes by utilizing microneedle arrays as a result of one of many world’s main consultants within the expertise was simply down the corridor. Burak Ozdoganlar, a professor of mechanical engineering, had been main efforts to develop completely different microneedles for greater than a decade with the late Lee Weiss, a professor in Carnegie Mellon’s Robotics Institute.

One of the unique inspirations for MNAs got here from Weiss, who conceptualized the thought of “micro-velcro,” or micro-barbs, an array of titanium initiatives within the form of an arrowhead. Ozdoganlar and Weiss labored collectively within the mid-2000s, creating manufacturing strategies to convey the “micro-velcro” to fruition. Later, Ozdoganlar collaborated with medical researchers from the University of Pittsburgh to reveal the applying of MNAs for a variety of ailments and circumstances together with pores and skin most cancers, and extra just lately, for COVID vaccination.

Yalcintas, a former Ph.D. pupil from Ozdoganlar’s analysis group, labored intently with Yerneni on the curcumin mission.

“This was a true collaboration between two outstanding research groups. Thanks to Ezgi and Sai’s excellent work, we successfully demonstrated the local delivery of curcumin to the skin and its efficacy in blocking and subsiding inflammation,” stated Ozdoganlar. “This can greatly impact treating a range of skin conditions, and possibly, various skin cancers.”

Published in Acta Biomaterialia, the workforce’s analysis demonstrates that the exosome/MNA hybrid system is an efficient method of delivering curcumin to the pores and skin. This will enable docs to make the most of curcumin as an all-natural therapeutic. The workforce has proven this to be an efficient therapy for decreasing native pores and skin irritation in small animal fashions, however additional analysis is required to discover curcumin’s different properties.

Next, the workforce plans to conduct additional experiments utilizing disease-specific animal fashions to show that the advantages of curcumin may be realized utilizing an exosome-albumin supply system and microneedle arrays.

“We successfully loaded exosome-albumin delivery system with curcumin,” Yerneni stated. “This technology is being extended to deliver other drugs and potentially control other skin diseases such as cancer (melanoma), psoriasis, and skin ulcers.”

SourceCarnegie Mellon University Mechanical Engineering

Yerneni SS, Yalcintas EP, Smith JD, Averick S, Campbell PG, Ozdoganlar OB. (2022) Skin-targeted delivery of extracellular vesicle-encapsulated curcumin using dissolvable microneedle arrays. Acta Biomater 149:198-212. [article]

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