Fabrication of biodegradable composite microneedles based on calcium sulfate and gelatin for transdermal delivery of insulin

Yang, Yuedong; Jiang, Guohua; Liu, Depeng; Li, Lei; Chen, Hua; Liu, Yongkun; Huang, Qin; Tong, Zaizai; Yao, Juming; Kong, Xiangdong

doi:10.1016/j.msec.2016.10.063

Cited by 104 publications

(65 citation statements)

References 45 publications

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“…After injecting the mice with the NPs, the released insulin can been used to determine the relative bioavailability [46,47]. Lei et al [48] manufactured a composite hydrogel system containing glucose-responsive nanocarriers for oral delivery of insulin and found the glucose-responsive nanocarriers can significantly prolong the time of insulin in the serum.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Phenylboronic acid-diol crosslinked 6-O-vinylazeloyl-d-galactose nanocarriers for insulin delivery

Bremner

et al. 2017

Materials Science and Engineering: C

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A new block polymer named poly 3-acrylamidophenylboronic acid-b-6-O-vinylazeloyl-d-galactose (p(AAPBA-b-OVZG)) was prepared using 3-acrylamidophenylboronic acid (AAPBA) and 6-O-vinylazeloyl-d-galactose (OVZG) via a two-step procedure involving S-1-dodecyl-S-(α', α'-dimethyl-α″-acetic acid) trithiocarbonate (DDATC) as chain transfer agent, 2,2-azobisisobutyronitrile (AIBN) as initiator and dimethyl formamide (DMF) as solvent. The structures of the polymer were examined by Fourier transform infrared spectroscopy (FT-IR) and H NMR and the thermal stability was determined by thermal gravimetric analysis (TG/DTG). Transmission electron microscopy (TEM) and dynamic light scattering (DLS) were utilized to evaluate the morphology and properties of the p(AAPBA-b-OVZG) nanoparticles. The cell toxicity, animal toxicity and therapeutic efficacy were also investigated. The results indicate the p(AAPBA-b-OVZG) was successfully synthesized and had excellent thermal stability. Moreover, the p(AAPBA-b-OVZG) nanoparticles were submicron in size and glucose-sensitive in phosphate-buffered saline (PBS). In addition, insulin as a model drug had a high encapsulation efficiency and loading capacity and the release of insulin was increased at higher glucose levels. Furthermore, the nanoparticles showed a low-toxicity in cell and animal studies and they were effective at decreasing blood glucose levels of mice over 96h. These p(AAPBA-b-OVZG) nanoparticles show promise for applications in diabetes treatment using insulin or other hypoglycemic proteins.

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Section: Accepted Manuscriptmentioning

confidence: 99%

Phenylboronic acid-diol crosslinked 6-O-vinylazeloyl-d-galactose nanocarriers for insulin delivery

Bremner

et al. 2017

Materials Science and Engineering: C

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“…To determine the storage stability of insulin solution encapsulated in TMAP, 150 μL insulin-loaded TMAP samples were stored at room temperature (approximately 25 °C) and at 4 °C for 90 d, respectively. Their bioactive insulin concentrations were measured using an insulin ELISA kit (Jianglai industrial Ltd., Shanghai, China), according to standard protocols (Yu et al., 2017a ; Yu et al., 2017c ).…”

Section: Methodsmentioning

confidence: 99%

Touch-actuated microneedle array patch for closed-loop transdermal drug delivery

et al. 2018

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To date, only approximately 20 drugs synthesized with small molecules have been approved by the FDA for use in traditional transdermal patches (TTP) owing to the extremely low permeation rate of the skin barrier for macromolecular drugs. A novel touch-actuated microneedle array patch (TMAP) was developed for transdermal delivery of liquid macromolecular drugs. TMAP is a combination of a typical TTP and a solid microneedle array (MA). High doses of liquid drug formulations, especially heat-sensitive compounds can be easily filled and stored in the drug reservoir of TMAPs. TMAP can easily penetrate the skin and automatically retract from it to create microchannels through the stratum corneum (SC) layer using touch-actuated ‘press and release’ actions for passive permeation of liquid drugs. Comparison of subcutaneous injection, TTP, solid MA, and dissolvable MA, indicated that insulin-loaded TMAP exhibited the best hypoglycemic effect on type 1 diabetic rats. A ‘closed-loop’ permeation control was also provided for on-demand insulin delivery based on feedback of blood glucose levels (BGLs). Twenty IU-insulin-loaded TMAP maintained the type 1 diabetic rats in a normoglycemic state for approximately 11.63 h, the longest therapeutic duration among all previously reported results on microneedle-based transdermal patches. TMAP possesses excellent transdermal drug delivery capabilities.

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“…Calcium compounds, calcium sulphate and hydroxyapatite are also attractive materials for fabrication of MNs. 75,76 Figure 4g shows a ceramic nanoporous MN array while Figure 4h shows bioceramic arrays attached to a flexible MN base made of gelatin. Ceramic MN are typically prepared using micromolding of a ceramic slurry followed by sintering at high temperatures.…”

Section: Established Materials For Mn Constructionmentioning

confidence: 99%

“…Gelatin in combination with other materials is also studied for MN fabrication. 75,76 Due to the absence of aromatic groups (no Tyr and Trp, and low Phe), gelatin is not antigenic. Like collagen, gelatin also degrades after swelling by the action of specific peptide cleaving enzymes.…”

Section: Polymersmentioning

confidence: 99%

Microneedle-based drug delivery: materials of construction

et al. 2019

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Microneedle-based drug delivery has attracted researchers' attention over the last decade. The material of construction of microneedles has emerged as a critical factor influencing clinical usage, manufacture, drug loading and drug stability. Initially, microneedles were fabricated using glass, silicon and metals. The development of sophisticated machining tools and advances in the polymer science allowed for a major shift in materials of construction of microneedles towards polymeric systems. Delivery of difficult to formulate therapeutics, including proteins, peptides, vaccines and genetic material has been established using microneedles. There is a constant search for newer materials, which can easily form microneedles with sufficient strength to penetrate biological barriers, can be easily manufactured, and are compatible with drug molecules and biological systems. While several reviews have discussed microneedle-based cosmetic and drug delivery applications, there is a gap in understanding the effect of material of construction of microneedles on drug stability and potential for large-scale manufacture. This review is an attempt to present microneedles as a function of the material used for its construction. Since microneedle commercialization is now a realistic possibility, we believe that improved understanding of materials and their chemistry will allow for improved decision making, especially for industries looking towards bringing microneedle technology to manufacturing setups.

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Fabrication of biodegradable composite microneedles based on calcium sulfate and gelatin for transdermal delivery of insulin

Cited by 104 publications

References 45 publications

Phenylboronic acid-diol crosslinked 6-O-vinylazeloyl-d-galactose nanocarriers for insulin delivery

Phenylboronic acid-diol crosslinked 6-O-vinylazeloyl-d-galactose nanocarriers for insulin delivery

Touch-actuated microneedle array patch for closed-loop transdermal drug delivery

Microneedle-based drug delivery: materials of construction

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