Microneedles for Extended Transdermal Therapeutics: A Route to Advanced Healthcare

Pahal, Suman; Badnikar, Kedar; Ghate, Vivek; Bhutani, Utkarsh; Nayak, M. M.; Subramanyam, Dinesh Narasimhaiah; Vemula, Praveen Kumar

doi:10.1016/j.ejpb.2020.12.020

Cited by 24 publications

(9 citation statements)

References 159 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous demonstrations of microneedles for insulin delivery have used in situ polymerization with covalent crosslinking performed within filled microneedle molds prior to drying. − This route introduces a risk of exposure to toxic unreacted monomers and crosslinking agents as well as (photo)initiators of polymerization. − However, loading a microneedle mold with preformed covalent polymer hydrogels is not feasible. A benefit of using dynamic-covalent hydrogels here is their ability to shear-thin and self-heal (Figure S8), allowing these materials to flow under applied mechanical force, fill voids or defects, and recover their original mechanical properties through dynamic bond rearrangement .…”

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery

Xiang

Monroe

et al. 2022

Biomacromolecules

View full text Add to dashboard Cite

The ongoing rise in diabetes incidence necessitates improved therapeutic strategies to enable precise blood glucose control with convenient device form factors. Microneedle patches are one such device platform capable of achieving therapeutic delivery through the skin. In recent years, polymeric microneedle arrays have been reported using methods of in situ polymerization and covalent crosslinking in microneedle molds. In spite of promising results, in situ polymerization carries a risk of exposure to toxic unreacted precursors remaining in the device. Here, a polymeric microneedle patch is demonstrated that uses dynamic-covalent phenylboronic acid (PBA)−diol bonds in a dual role affording both network crosslinking and glucose sensing. By this approach, a pre-synthesized and purified polymer bearing pendant PBA motifs is combined with a multivalent diol crosslinker to prepare dynamic-covalent hydrogel networks. The ability of these dynamic hydrogels to shear-thin and self-heal enables their loading to a microneedle mold by centrifugation. Subsequent drying then yields a patch of uniformly shaped microneedles with the requisite mechanical properties to penetrate skin. Insulin release from these materials is accelerated in the presence of glucose. Moreover, short-term blood glucose control in a diabetic rat model following application of the device to the skin confirms insulin activity and bioavailability. Accordingly, dynamic-covalent crosslinking facilitates a route for fabricating microneedle arrays circumventing the toxicity concerns of in situ polymerization, offering a convenient device form factor for therapeutic insulin delivery.

show abstract

Section: Resultsmentioning

confidence: 99%

“…However, such microneedles are typically prepared using in situ covalent polymerization techniques that yield non-degradable chemically crosslinked polymer networks prepared within microneedle molds. Such a process introduces risks for physiological exposure to toxic unreacted monomers, crosslinkers, or initiators of polymerization. − …”

Section: Introductionmentioning

confidence: 99%

Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery

Xiang

Monroe

et al. 2022

Biomacromolecules

View full text Add to dashboard Cite

show abstract

“…[ 10 ] However, the microneedle tips escort drugs to the destination by creating micro‐channels in the skin, which in turn expose the skin to toxic chemicals such as diffusive monomers if the material is not thoroughly cleaned, limiting matrix design to only a few biocompatible polymers or copolymers free of toxic monomer residues. [ 11 ] Additionally, the drug release mechanism mainly utilizes the solvent dissolvable or deformable properties of the polymeric matrixes, which hinders the pre‐administration of the purification process. [ 12 ] Despite the different purposes of the microneedle, mold‐assisted fabrication is the dominant method.…”

Section: Introductionmentioning

confidence: 99%

Shrinking Fabrication of a Glucose‐Responsive Glucagon Microneedle Patch

Wang

Han

et al. 2022

Advanced Science

View full text Add to dashboard Cite

A microdevice that offers glucagon supplements in a safe, non-invasive, and glucose-responsive manner is ideal for avoiding fatal hypoglycemia consequences from insulin overdosage during daily diabetes treatment. However, mold-assisted microfabrication of biomedical materials or devices typically needs high-resolution laser ablation to scale down structural design. In addition, the majority of the polymeric drug delivery materials being used to fabricate devices are dissolvable or deformable in aqueous environments, which restricts washing-based cleaning and purification procedures post shape fixation. This study leverages the design flexibility of 3D printing-assisted mold casting and presents a shrinking microfabrication approach that allows subsequent washing procedures to remove toxic monomer residues during polymerization. The feasibility of this approach is demonstrated by developing a glucose-responsive transdermal glucagon microneedle patch through matrix volume change-mediated release kinetic control. Shown in the type 1 diabetic mouse model, this transdermal patch can reverse the occurrence of hypoglycemia while lowering the risk of monomer residue-induced irritation during treatment. Freeing from the restrain of molding resolution for microstructure design, this shrinking methodology further provides an insight into post-fabrication purifications of biomedical materials.

show abstract

“…[13] A microneedle array-based patch is an attractive option for a minimally invasive mean for the transdermal delivery of drugs, hormones, and vaccines. [9][10][11][14][15][16][17][18][19][20][21] The drugs and vaccines can be delivered by a coating on conventional solid needles, or by incorporating them within needles made of dissolvable polymers. [14][15][16][17][18][19][20][21] However, these types of microneedles have limited application due to their low drug loading/release capacity.…”

Section: Introductionmentioning

confidence: 99%

“…[9][10][11][14][15][16][17][18][19][20][21] The drugs and vaccines can be delivered by a coating on conventional solid needles, or by incorporating them within needles made of dissolvable polymers. [14][15][16][17][18][19][20][21] However, these types of microneedles have limited application due to their low drug loading/release capacity. [9] Another type of microneedle is the porous microneedle (PMN) [22][23][24][25][26][27][28][29][30][31][32] which has a micro-/nanochannel network throughout the whole needle, thereby providing a large storage capacity for pharmaceutical formulations.…”

Section: Introductionmentioning

confidence: 99%

Porous Microneedle Patch for Electroosmosis‐Promoted Transdermal Delivery of Drugs and Vaccines

Abe

Sato

Kimura

et al. 2021

Advanced NanoBiomed Research

View full text Add to dashboard Cite

A charged porous microneedle (PMN) generates the electroosmotic flow (EOF) and promotes the through‐needle transport of molecules and particles, indicating its applicability for the EOF‐based low‐invasive transdermal delivery of drugs and vaccines. The negatively charged PMN is prepared by grafting a thin film of poly (2‐acrylamido‐2‐methylpropanesulfonic acid) (PAMPS) onto the inner wall of the microchannels of the polyglycidyl methacrylate PMN. Promoted transport from anode to cathode is observed for albumin, Au nanoparticles (15, 50 nm), and silica beads (100 nm), indicating the generation of an EOF strong enough to transport these negatively charged larger size species against their electrophoretic motion. A model antigen ovalbumin (OVA) is preloaded in the PMN, and is injected to a hydrogel and a pig skin with a higher efficiency (more than 2 times) than the conventional diffusion‐based passive release. These results successfully demonstrate the novel EOF‐based effective injection of drugs and vaccines into the skin, achieved by the newly developed charged PMN.

show abstract

Microneedles for Extended Transdermal Therapeutics: A Route to Advanced Healthcare

Cited by 24 publications

References 159 publications

Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery

Polymeric Microneedle Arrays with Glucose-Sensing Dynamic-Covalent Bonding for Insulin Delivery

Shrinking Fabrication of a Glucose‐Responsive Glucagon Microneedle Patch

Porous Microneedle Patch for Electroosmosis‐Promoted Transdermal Delivery of Drugs and Vaccines

Contact Info

Product

Resources

About