Research

13 pages, 3486 KiB

Open AccessArticle

Biocontrol Microneedle Patch: A Promising Agent for Protecting Citrus Fruits from Postharvest Infection

by Ling Jiang, Huan Huang, Xingyu Shi, Jian Wu, Juexian Ye, Qian Xu, Shaobin Fang, Chuanbin Wu, Rui Luo, Chao Lu and Daojun Liu

Pharmaceutics 2023, 15(4), 1219; https://doi.org/10.3390/pharmaceutics15041219 - 11 Apr 2023

Cited by 1 | Viewed by 1596

Abstract

With increasing human awareness of food safety, the replacement of highly toxic pesticides with biocompatible antimicrobials has become a trend. This study proposes a biocontrol microneedle (BMN) to expand the application of the food-grade preservative epsilon-poly-L-lysine (ε-PL) in fruit preservatives by utilizing a [...] Read more.

With increasing human awareness of food safety, the replacement of highly toxic pesticides with biocompatible antimicrobials has become a trend. This study proposes a biocontrol microneedle (BMN) to expand the application of the food-grade preservative epsilon-poly-L-lysine (ε-PL) in fruit preservatives by utilizing a dissolving microneedle system. The macromolecular polymer ε-PL not only possesses broad-spectrum antimicrobial activity but also exhibits good mechanical properties. With the addition of a small amount of polyvinyl alcohol, the mechanical strength of the ε-PL-based microneedle patch could be further improved to achieve an enhanced failure force of needles at 1.6 N/needle and induce an approximately 96% insertion rate in citrus fruit pericarps. An ex vivo insertion test revealed that the microneedle tips could be effectively inserted into the citrus fruit pericarp, rapidly dissolve within 3 min, and produce inconspicuous needle holes. Moreover, the high drug loading capacity of BMN was observed to reach approximately 1890 μg/patch, which is essential for enhancing the concentration-dependent antifungal activity of ε-PL. The drug distribution study has confirmed the feasibility of mediating the local diffusion of EPL in the pericarp through BMN. Therefore, BMN has great potential to reduce the incidence of invasive fungal infections in local areas of citrus fruit pericarp. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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15 pages, 3678 KiB

Open AccessArticle

An Adjuvanted Inactivated SARS-CoV-2 Microparticulate Vaccine Delivered Using Microneedles Induces a Robust Immune Response in Vaccinated Mice

by Sharon Vijayanand, Smital Patil, Ipshita Menon, Keegan Braz Gomes, Akanksha Kale, Priyal Bagwe, Mohammad N. Uddin, Susu M. Zughaier and Martin J. D’Souza

Pharmaceutics 2023, 15(3), 895; https://doi.org/10.3390/pharmaceutics15030895 - 09 Mar 2023

Cited by 5 | Viewed by 2621

Abstract

SARS-CoV-2, the causal agent of COVID-19, is a contagious respiratory virus that frequently mutates, giving rise to variant strains and leading to reduced vaccine efficacy against the variants. Frequent vaccination against the emerging variants may be necessary; thus, an efficient vaccination system is [...] Read more.

SARS-CoV-2, the causal agent of COVID-19, is a contagious respiratory virus that frequently mutates, giving rise to variant strains and leading to reduced vaccine efficacy against the variants. Frequent vaccination against the emerging variants may be necessary; thus, an efficient vaccination system is needed. A microneedle (MN) vaccine delivery system is non-invasive, patient-friendly, and can be self-administered. Here, we tested the immune response produced by an adjuvanted inactivated SARS-CoV-2 microparticulate vaccine administered via the transdermal route using a dissolving MN. The inactivated SARS-CoV-2 vaccine antigen and adjuvants (Alhydrogel^® and AddaVax™) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) polymer matrices. The resulting MP were approximately 910 nm in size, with a high percentage yield and percent encapsulation efficiency of 90.4%. In vitro, the vaccine MP was non-cytotoxic and increased the immunostimulatory activity measured as nitric oxide release from dendritic cells. The adjuvant MP potentiated the immune response of the vaccine MP in vitro. In vivo, the adjuvanted SARS-CoV-2 MP vaccine induced high levels of IgM, IgG, IgA, IgG1, and IgG2a antibodies and CD4⁺ and CD8⁺ T-cell responses in immunized mice. In conclusion, the adjuvanted inactivated SARS-CoV-2 MP vaccine delivered using MN induced a robust immune response in vaccinated mice. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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14 pages, 7098 KiB

Open AccessArticle

Demonstrating Biological Fate of Nanoparticle-Loaded Dissolving Microneedles with Aggregation-Caused Quenching Probes: Influence of Application Sites

by Yanping Fu, Chaonan Shi, Xiaodie Li, Ting Wen, Qiaoli Wu, Antian Zhang, Ping Hu, Chuanbin Wu, Xin Pan, Zhengwei Huang and Guilan Quan

Pharmaceutics 2023, 15(1), 169; https://doi.org/10.3390/pharmaceutics15010169 - 03 Jan 2023

Cited by 2 | Viewed by 1991

Abstract

Integrating dissolving microneedles (DMNs) and nanocarriers (NC) holds great potential in transdermal drug delivery because it can simultaneously overcome the stratum corneum barrier and achieve efficient and controlled drug delivery. However, different skin sites with different thicknesses and compositions can affect the transdermal [...] Read more.

Integrating dissolving microneedles (DMNs) and nanocarriers (NC) holds great potential in transdermal drug delivery because it can simultaneously overcome the stratum corneum barrier and achieve efficient and controlled drug delivery. However, different skin sites with different thicknesses and compositions can affect the transdermal diffusion of NC-loaded DMNs. There are few reports on the biological fate (especially transdermal diffusion) of NC-loaded DMNs, and inaccurate bioimaging information of intact NC limits the accurate understanding of the in vivo fate of NC-loaded DMNs. The aggregation-caused quenching (ACQ) probes P4 emitted intense fluorescence signals in intact NC while quenched after the degradation of NC, had been demonstrated the feasibility of label intact NC. In this study, P4 was loaded in solid lipid nanoparticles (SLNs), and further encapsulated into DMNs, to track the transdermal diffusion of SLNs delivered at different skin sites. The results showed that SLNs had excellent stability after being loaded into DMNs with no significant changes in morphology and fluorescence properties. The in vivo live and ex vivo imaging showed that the transdermal diffusion rate of NC-loaded DMNs was positively correlated with skin thickness, with the order ear > abdomen > back. In conclusion, this study confirmed the site-dependency of transdermal diffusion in NC-loaded DMNs. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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11 pages, 3828 KiB

Open AccessArticle

Promotion of Hair Regrowth by Transdermal Dissolvable Microneedles Loaded with Rapamycin and Epigallocatechin Gallate Nanoparticles

by Yali Lin, Ruomei Shao, Tong Xiao and Shuqing Sun

Pharmaceutics 2022, 14(7), 1404; https://doi.org/10.3390/pharmaceutics14071404 - 04 Jul 2022

Cited by 7 | Viewed by 3886

Abstract

Interest in transdermal delivery methods for stimulating hair regrowth has been increasing recently. The microneedle approach can break the barrier of the stratum corneum through puncture ability and improve drug delivery efficiency. Herein, we report a dissolvable microneedle device for the co-delivery of [...] Read more.

Interest in transdermal delivery methods for stimulating hair regrowth has been increasing recently. The microneedle approach can break the barrier of the stratum corneum through puncture ability and improve drug delivery efficiency. Herein, we report a dissolvable microneedle device for the co-delivery of rapamycin and epigallocatechin gallate nanoparticles that can significantly promote hair regeneration. Compared with the mice without any treatment, our strategy can facilitate hair growth within 7 days. Higher hair shaft growth rate and hair follicle density with inconspicuous inflammation were exhibited in C57BL/6 mice, elucidating its potential for clinical application. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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18 pages, 5783 KiB

Open AccessArticle

A Novel Approach for Skin Regeneration by a Potent Bioactive Placental-Loaded Microneedle Patch: Comparative Study of Deer, Goat, and Porcine Placentas

by Kritsanaporn Tansathien, Phuvamin Suriyaamporn, Tanasait Ngawhirunpat, Praneet Opanasopit and Worranan Rangsimawong

Pharmaceutics 2022, 14(6), 1221; https://doi.org/10.3390/pharmaceutics14061221 - 08 Jun 2022

Cited by 3 | Viewed by 3057

Abstract

The aims of this study were to investigate the skin regeneration potential of bioactive placenta (deer placenta (DP), goat placenta (GP), and porcine placenta (PP)) and fabricate bioactive extract-loaded dissolving microneedles (DMNs) as a dermal delivery approach. The placentas were water-extracted, and the [...] Read more.

The aims of this study were to investigate the skin regeneration potential of bioactive placenta (deer placenta (DP), goat placenta (GP), and porcine placenta (PP)) and fabricate bioactive extract-loaded dissolving microneedles (DMNs) as a dermal delivery approach. The placentas were water-extracted, and the active compounds were evaluated. Bioactivity studies were performed in dermal fibroblasts and keratinocytes. DMNs were fabricated to deliver the potent bioactive placenta extract into the skin. All placental extracts expressed high amounts of protein, growth factors (EGF, FGF, IGF-1 and TGF-β1), and amino acids. These extracts were not toxic to the skin cells, while the proliferation of fibroblast cells significantly increased in a time-dependent manner. GP extract that exhibited the maximum proliferation, migration, and regeneration effect on fibroblast cells was loaded into DMN patch. The suitable physical properties of DMNs led to increased skin permeation and deposition of bioactive macromolecules. Moreover, GP extract-loaded DMNs showed minimal invasiveness to the skin and were safe for application to human skin. In conclusion, placental extracts act as potent bioactive compounds for skin cells, and the highest bioactive potential of GP-loaded DMNs might be a novel approach to regenerate the skin. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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Review

Jump to: Research, Other

23 pages, 4901 KiB

Open AccessReview

Silk Fibroin Microneedles for Transdermal Drug Delivery: Where Do We Stand and How Far Can We Proceed?

by Zhenzhen Qi, Zheng Yan, Guohongfang Tan, Tianshuo Jia, Yiyu Geng, Huiyan Shao, Subhas C. Kundu and Shenzhou Lu

Pharmaceutics 2023, 15(2), 355; https://doi.org/10.3390/pharmaceutics15020355 - 20 Jan 2023

Cited by 10 | Viewed by 4336

Abstract

Microneedles are a patient-friendly technique for delivering drugs to the site of action in place of traditional oral and injectable administration. Silk fibroin represents an interesting polymeric biomaterial because of its mechanical properties, thermal stability, biocompatibility and possibility of control via genetic engineering. [...] Read more.

Microneedles are a patient-friendly technique for delivering drugs to the site of action in place of traditional oral and injectable administration. Silk fibroin represents an interesting polymeric biomaterial because of its mechanical properties, thermal stability, biocompatibility and possibility of control via genetic engineering. This review focuses on the critical research progress of silk fibroin microneedles since their inception, analyzes in detail the structure and properties of silk fibroin, the types of silk fibroin microneedles, drug delivery applications and clinical trials, and summarizes the future development trend in this field. It also proposes the future research direction of silk fibroin microneedles, including increasing drug loading doses and enriching drug loading types as well as exploring silk fibroin microneedles with stimulation-responsive drug release functions. The safety and effectiveness of silk fibroin microneedles should be further verified in clinical trials at different stages. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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44 pages, 10378 KiB

Open AccessReview

Recent Advancements in Microneedle Technology for Multifaceted Biomedical Applications

by Deepak Kulkarni, Fouad Damiri, Satish Rojekar, Mehrukh Zehravi, Sarker Ramproshad, Dipali Dhoke, Shubham Musale, Ashiya A. Mulani, Pranav Modak, Roshani Paradhi, Jyotsna Vitore, Md. Habibur Rahman, Mohammed Berrada, Prabhanjan S. Giram and Simona Cavalu

Pharmaceutics 2022, 14(5), 1097; https://doi.org/10.3390/pharmaceutics14051097 - 20 May 2022

Cited by 44 | Viewed by 8003

Abstract

Microneedle (MNs) technology is a recent advancement in biomedical science across the globe. The current limitations of drug delivery, like poor absorption, low bioavailability, inadequate skin permeation, and poor biodistribution, can be overcome by MN-based drug delivery. Nanotechnology made significant changes in fabrication [...] Read more.

Microneedle (MNs) technology is a recent advancement in biomedical science across the globe. The current limitations of drug delivery, like poor absorption, low bioavailability, inadequate skin permeation, and poor biodistribution, can be overcome by MN-based drug delivery. Nanotechnology made significant changes in fabrication techniques for microneedles (MNs) and design shifted from conventional to novel, using various types of natural and synthetic materials and their combinations. Nowadays, MNs technology has gained popularity worldwide in biomedical research and drug delivery technology due to its multifaceted and broad-spectrum applications. This review broadly discusses MN’s types, fabrication methods, composition, characterization, applications, recent advancements, and global intellectual scenarios. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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Other

Jump to: Research, Review

19 pages, 2739 KiB

Open AccessSystematic Review

Microneedles in Advanced Microfluidic Systems: A Systematic Review throughout Lab and Organ-on-a-Chip Applications

by Renata Maia, Violeta Carvalho, Rui Lima, Graça Minas and Raquel O. Rodrigues

Pharmaceutics 2023, 15(3), 792; https://doi.org/10.3390/pharmaceutics15030792 - 28 Feb 2023

Cited by 6 | Viewed by 3050

Abstract

Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a stand-alone tool to be combined with microfluidic devices. For that purpose, lab- or organ-on-a-chip are being developed. This systematic [...] Read more.

Microneedles (MNs) have been widely used in biomedical applications for drug delivery and biomarker detection purposes. Furthermore, MNs can also be used as a stand-alone tool to be combined with microfluidic devices. For that purpose, lab- or organ-on-a-chip are being developed. This systematic review aims to summarize the most recent progress in these emerging systems, to identify their advantages and limitations, and discuss promising potential applications of MNs in microfluidics. Therefore, three databases were used to search papers of interest, and their selection was made following the guidelines for systematic reviews proposed by PRISMA. In the selected studies, the MNs type, fabrication strategy, materials, and function/application were evaluated. The literature reviewed showed that although the use of MNs for lab-on-a-chip has been more explored than for organ-on-a-chip, some recent studies have explored this applicability with great potential for the monitoring of organ models. Overall, it is shown that the presence of MNs in advanced microfluidic devices can simplify drug delivery and microinjection, as well as fluid extraction for biomarker detection by using integrated biosensors, which is a promising tool to precisely monitor, in real-time, different kinds of biomarkers in lab- and organ-on-a-chip platforms. Full article

(This article belongs to the Special Issue Recent Advances in Microneedle-Mediated Drug Delivery)

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