Ring inserts as a useful strategy to prepare tip-loaded microneedles for long-acting drug delivery with application in HIV pre-exposure prophylaxis

Paredes, Alejandro J.; Permana, Andi Dian; Volpe‐Zanutto, Fabiana; Amir, Muhammad Nur; Vora, Lalitkumar K.; Tekko, Ismaiel; Akhavein, Nima; Weber, Andrew; Larrañeta, Eneko; Donnelly, Ryan F.

doi:10.1016/j.matdes.2022.111416

Cited by 21 publications

(11 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The majority of the drug was detected in the viable skin, while only a small amount (always less than 5 µg) reached the receptor cells, which was expected due to meloxicam's hydrophobic properties. As noted in previous studies, [ 27 ] it is advantageous if a more significant amount of the drug is deposited in the skin since this has the potential to make the drug more effective for a more extended period while simplifying dosing regimens. The MxMNs4h formulation exhibited a more gradual drug release rate, as already evidenced by the in vitro release study.…”

Section: Resultsmentioning

confidence: 99%

Double‐Layered Polyvinylpyrrolidone–Poly(methyl vinyl ether‐alt‐maleic acid)‐Based Microneedles to Deliver Meloxicam: An In Vitro, In Vivo, and Short‐Term Stability Evaluation Study

D'Amico

Fontana

El‐Sayed

et al. 2023

Advanced Therapeutics

View full text Add to dashboard Cite

This study aims to explore the use of polymeric microneedles (MNs) for the transdermal delivery of drugs, a noninvasive and convenient method that avoids first-pass metabolism and gastrointestinal complications. Specifically, a double-layered MN formulation is developed using polyvinylpyrrolidone and cross-linked poly(methyl vinyl ether-alt-maleic acid), comprising a dissolvable layer and a hydrogel-forming layer. Meloxicam serves as the model drug, and no organic solvents are employed in the manufacturing process to reduce toxicity. Coherent anti-Stokes Raman spectroscopy (CARS) is utilized to confirm that the manufacturing process does not alter the drug's physical properties. In vitro and ex vivo studies demonstrate that the double-layered MN formulation exhibits faster drug release in the first few hours, followed by a slower release. This results in extended bioavailability in vivo compared to the commercial oral formulation of meloxicam. Preliminary results indicate that the MN formulation is also effective in pain relief and inflammation reduction. The short-term stability of the MN formulation is also confirmed, including its mechanical properties, sustained skin permeability, drug physical properties and distribution within MNs using CARS microscopy. Overall, these results suggest that the double-layered MN formulation holds significant potential for transdermal drug delivery, offering a safer and more effective alternative to traditional oral administration.

show abstract

Section: Resultsmentioning

confidence: 99%

Double‐Layered Polyvinylpyrrolidone–Poly(methyl vinyl ether‐alt‐maleic acid)‐Based Microneedles to Deliver Meloxicam: An In Vitro, In Vivo, and Short‐Term Stability Evaluation Study

D'Amico

Fontana

El‐Sayed

et al. 2023

Advanced Therapeutics

View full text Add to dashboard Cite

show abstract

“…The mechanical and insertion properties were determined by attaching a MAP to a cylindrical probe of a TA. An XT2 texture analyzer (Stable Micro Systems., Ltd., Haslemere, UK) in compression mode was used as previously described. , The probe was moved vertically downward at a speed of 0.5 mm/s to compress the MAP with a force of 32 N for 30 s. A flat aluminum block was used against the MAP to test its mechanical properties. Before and after compression, the length of each individual needle in the MAPs was measured.…”

Section: Methodsmentioning

confidence: 99%

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies

Dai,

Permana,

et al. 2024

Mol. Pharmaceutics

Self Cite

View full text Add to dashboard Cite

Psoriasis, affecting 2−3% of the global population, is a chronic inflammatory skin condition without a definitive cure. Current treatments focus on managing symptoms. Recognizing the need for innovative drug delivery methods to enhance patient adherence, this study explores a new approach using calcipotriol monohydrate (CPM), a primary topical treatment for psoriasis. Despite its effectiveness, CPM's therapeutic potential is often limited by factors like the greasiness of topical applications, poor skin permeability, low skin retention, and lack of controlled delivery. To overcome these challenges, the study introduces CPM in the form of nanosuspensions (NSs), characterized by an average particle size of 211 ± 2 nm. These CPM NSs are then incorporated into a trilayer dissolving microneedle patch (MAP) made from poly(vinylpyrrolidone) and w poly(vinyl alcohol) as needle arrays and prefrom 3D printed polylactic acid backing layer. This MAP features rapidly dissolving tips and exhibits good mechanical properties and insertion capability with delivery efficiency compared to the conventional Daivonex ointment. The effectiveness of this novel MAP was tested on Sprague−Dawley rats with imiquimod-induced psoriasis, demonstrating efficacy comparable to the marketed ointment. This innovative trilayer dissolving MAP represents a promising new local delivery system for calcipotriol, potentially revolutionizing psoriasis treatment by enhancing drug delivery and patient compliance.

show abstract

“…Nevertheless, the drug deposition study conducted in this research from full-thickness porcine skin did not depict the level of drug in each layer of the skin (SC, epidermis and dermis); therefore, it is difficult to predict the DFS gradient and availability of DFS for immediate systemic release or sustained effect of the DFS. However, based on previous work from our research group with similar type of hydrophobic drugs (cabotegravir, rilpivirine), DFS NS deposited intradermally with dissolution as well as skin rate-limiting factor for the sustained release [51][52][53][54] could allow the reduction of the frequency of DFS dose administration. However, to prove the sustained delivery effect, further in vivo research is needed.…”

Section: Determination Of Skin Penetrationmentioning

confidence: 99%

Deferasirox Nanosuspension Loaded Dissolving Microneedles for Intradermal Delivery

et al. 2022

Self Cite

View full text Add to dashboard Cite

Microneedles are minimally invasive systems that can deliver drugs intradermally without pain and bleeding and can advantageously replace the hypodermal needles and oral routes of delivery. Deferasirox (DFS) is an iron chelator employed in several ailments where iron overload plays an important role in disease manifestation. In this study, DFS was formulated into a nanosuspension (NSs) through wet media milling employing PVA as a stabilizer and successfully loaded in polymeric dissolving microneedles (DMNs). The release studies for DFS-NS clearly showed a threefold increased dissolution rate compared to pure DFS. The mechanical characterization of DFS-NS-DMNs revealed that the system was sufficiently strong for efficacious skin penetration. Optical coherence tomography images confirmed an insertion of up to 378 µm into full-thickness porcine skin layers. The skin deposition studies showed 60% drug deposition from NS-DMN, which was much higher than from the DFS-NS transdermal patch (DFS-NS-TP) (without needles) or pure DFS-DMNs. Moreover, DFS-NS without DMNs did not deposit well inside the skin, indicating that DMNs played an important role in effectively delivering drugs inside the skin. Therefore, it is evident from the findings that loading DFS-NS into novel DMN devices can effectively deliver DFS transdermally.

show abstract

Ring inserts as a useful strategy to prepare tip-loaded microneedles for long-acting drug delivery with application in HIV pre-exposure prophylaxis

Cited by 21 publications

References 33 publications

Double‐Layered Polyvinylpyrrolidone–Poly(methyl vinyl ether‐alt‐maleic acid)‐Based Microneedles to Deliver Meloxicam: An In Vitro, In Vivo, and Short‐Term Stability Evaluation Study

Double‐Layered Polyvinylpyrrolidone–Poly(methyl vinyl ether‐alt‐maleic acid)‐Based Microneedles to Deliver Meloxicam: An In Vitro, In Vivo, and Short‐Term Stability Evaluation Study

Calcipotriol Nanosuspension-Loaded Trilayer Dissolving Microneedle Patches for the Treatment of Psoriasis: In Vitro Delivery and In Vivo Antipsoriatic Activity Studies

Deferasirox Nanosuspension Loaded Dissolving Microneedles for Intradermal Delivery

Contact Info

Product

Resources

About