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Ros-responsive microneedle patch for acne vulgaris treatment

A responsive, therapeutic technology for the preparation of microneedle arrays, compositions comprising absorbent materials, microneedle arrays and skin patches, for the treatment of acne or other inflammatory/infectious skin diseases, in the field of microneedles, capable of Solve the problems of intestinal flora damage, adverse side effects, teratogenic effects, etc.

Pending Publication Date: 2021-01-08
NORTH CAROLINA STATE UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the effectiveness of these creams may be limited due to the inefficiency of drug delivery to foci within the pilosebaceous gland
Acne is also treated with oral antibiotics, but this can lead to adverse side effects, including damage to gut flora and teratogenic effects

Method used

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  • Ros-responsive microneedle patch for acne vulgaris treatment
  • Ros-responsive microneedle patch for acne vulgaris treatment
  • Ros-responsive microneedle patch for acne vulgaris treatment

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0198] Preparation of ROS-responsive hydrogels

[0199] All chemicals were purchased from Sigma-Aldrich (St. Lious, Missouri, United States of America) and used as received unless otherwise stated. Purification system by Millipore NanoPure (MilliporeSigma, Burlington, Massachusetts, United States of America, resistivity higher than 18.2MΩcm -1 ) to prepare deionized water.

[0200] Synthesis of ROS-responsive crosslinker (TSPBA): 4-(bromomethyl)phenylboronic acid (1 g, 4.6 mmol) and N,N,N',N'-tetramethyl-1,3-propanediamine (0.2 g, 1.5 mmol) was dissolved in dimethylformamide (DMF; 40 mL), and the solution was stirred at 60° C. for 24 h. Afterwards, the mixture was poured into tetrahydrofuran (THF, 100 mL), filtered, and washed with THF (3 x 20 mL). After drying under vacuum overnight, pure TSPBA was obtained (0.6 g, 70% yield). 1 H-NMR (300MHz, D 2 O, δ): 7.677 (d, 4H), 7.395 (d, 4H), 4.409 (s, 4H), 3.232 (t, 4H), 2.936 (s, 6H), 2.81 (m, 2H). The synthetic route and struct...

Embodiment 2

[0206] In vitro results of ROS-responsive hydrogels

[0207] In vitro release profile: by dissolving the hydrogel in 12mL PBS buffer (NaCl, 137mM; KCl, 2.7mM; Na 2 HPO 4 , 10mM; KH 2 PO 4 , 2mM, pH 7.4), incubated on an orbital shaker at 37°C, to which was added H 2 o 2 Up to a concentration of 1 mM, the in vitro release profile of CDM released from RR-PVA gel was evaluated. At predetermined time points, the concentration of CDM in the supernatant was determined by high performance liquid chromatography (HPLC). On the Zorbax Eclipse Plus RRHD C18 column (2.1 × 50mm, 1.8μm particle size) (Agilent Technologies, Santa Clara, California, United States of America) using 80% water (HPLC grade, containing 0.1% v / v trifluoroacetic acid ) and 20% acetonitrile (HPLC grade, containing 0.1% v / v trifluoroacetic acid) was used to analyze samples at 205 nanometers (nm). Cumulative release (%) is expressed as a percentage of total drug released over time.

[0208] Antibacterial effect...

Embodiment 3

[0213] Preparation of ROS-responsive microneedle patch

[0214] Preparation of ROS-responsive (RR) microneedle patches: All MN patches in this study were prepared using homogeneous silicone molds from Blueacre Technology Ltd (Dundalk, Ireland). There is an array of 11 x 11 needles in the mold, each needle has a height of 600 μm and a circular base diameter of 300 μm. The tip-to-tip spacing is 600 μm. First, PVAMNs were formed by pipetting a premixed PVA (3 wt%) / TSPBA (3 wt%) (ratio 3:1) solution (400 μL) onto the MN mold surface. The mold was kept under vacuum (600mmHg) for 30 minutes to allow the solution to deposit into the MN cavity. Afterwards, the covered mold was centrifuged at 500 rpm for 20 minutes using a Hettich Universal 32R centrifuge (Hettich GmbH & Co. KG, Tuttlingen, Germany) to concentrate the PVA network in the MN. In the first step, drug-loaded MNs were fabricated by adding a predetermined amount of drug in the PVA / TSPBA solution. Non-responsive (NR) micr...

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Abstract

A composition comprising a bioresponsive (e.g., reactive oxygen species (ROS)-responsive), antibiotic- and / or absorbent-loaded polymeric network is described. In some cases, the composition can release the antibiotic loaded therein in response to ROS or another stimulus related to inflammation. Microneedles, microneedle arrays, and skin patches comprising the composition are also described, as well as methods of treating acne or other inflammatory / infectious skin conditions.

Description

[0001] related application [0002] This application claims priority and benefit to U.S. Provisional Patent Application Serial No. 62 / 657,313, filed April 13, 2018; the disclosure of which is incorporated herein by reference in its entirety. technical field [0003] The subject matter of the present disclosure relates to compositions for bioresponsive delivery of antibiotic agents and / or compositions comprising absorbent materials. The composition may comprise a biodegradable polymer, such as polyester, and / or a cross-linked hydrophilic polymer cross-linked with multiple bioresponsive linkers, wherein the composition further comprises an antibiotic or an antibiotic-loaded carrier . A bioresponsive linker can respond to inflammation and / or reactive oxygen species (ROS). The disclosed subject matter also relates to microneedles, microneedle arrays, and skin patches comprising the composition; also to methods of making microneedle arrays; and to methods of treating acne or othe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/70A61K31/4025A61K31/04
CPCA61K31/7056A61K33/40A61K33/06A61K45/06A61K9/0021A61K47/02A61K9/06A61K47/34A61K47/32A61K47/36A61K47/18A61P17/10A61P31/04A61M37/0015A61M2037/0023A61M2037/0061A61M2037/0046A61K47/58A61K47/61A61K47/6903A61K47/6955A61K31/155A61K31/20A61K31/203A61K31/235A61K38/10A61M35/006A61M2037/0053
Inventor 顾臻张宇琪
Owner NORTH CAROLINA STATE UNIV
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