Hydrogel-forming microarray patches with cyclodextrin drug reservoirs for long-acting delivery of poorly soluble cabotegravir sodium for HIV Pre-Exposure Prophylaxis

Volpe‐Zanutto, Fabiana; Vora, Lalitkumar K.; Tekko, Ismaiel; McKenna, Peter E.; Permana, Andi Dian; Sabri, Akmal Hidayat Bin; Anjani, Qonita Kurnia; McCarthy, Helen; Paredes, Alejandro J.; Donnelly, Ryan F.

doi:10.1016/j.jconrel.2022.06.028

Cited by 45 publications

(21 citation statements)

References 41 publications

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“…Briefly, the amount of each ingredient was blended using a mortar and pestle. The obtained powder was pressed to produce a 300 mg tablet with a diameter of 10 mm and a thickness of 3.5 mm …”

Section: Methodsmentioning

confidence: 99%

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Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan

Enggi,

Sulistiawati,

Himawan

et al. 2024

ACS Biomater. Sci. Eng.

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However, its oral application is limited by its poor water solubility. This study presents the successful utilization of biomaterial-based hydrogelforming microneedles integrated with a direct compressed tablet reservoir (HFMN-DCT) for the transdermal delivery of telmisartan in the treatment of hypertension. The combination of PVP, PVA, and tartaric acid was used in the HFMN formulation. A range of cross-linking temperatures and times were employed to optimize the characteristics of the HFMN. The HFMN exhibited excellent swelling capacity, mechanical strength, and insertion properties. Additionally, the poorly soluble characteristic of TEL was improved by the inclusion complex formulation with β-cyclodextrin (βCD). Phase solubility analysis showed an A p -type diagram, indicating a higher-order complex between TEL and βCD, with respect to βCD. A ratio of TEL:βCD of 1:4 mM demonstrates the highest solubility enhancement of TEL. The inclusion complex formation was confirmed by FTIR, XRD, DSC, and molecular docking studies. A significantly higher release of TEL (up to 20-fold) from the inclusion complex was observed in the in vitro release study. Subsequently, a DCT reservoir was developed using various concentrations of sodium starch glycolate. Essentially, both the HFMN and DCT reservoir exhibit hemocompatibility and did not induce any skin irritation. The optimized combination of the HFMN-DCT reservoir showed an ex vivo permeation profile of 83.275 ± 2.405%. Notably, the proposed system showed superior pharmacokinetic profiles in the in vivo investigation using male Wistar rats. Overall, this study highlights the potential of HFMN-DCT reservoir systems as a versatile platform for transdermal drug delivery applications.

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Section: Methodsmentioning

confidence: 99%

“…The obtained powder was pressed to produce a 300 mg tablet with a diameter of 10 mm and a thickness of 3.5 mm. 46 2.23. Physical Characteristics of the DCT Reservoir.…”

Section: Fourier Transform Infrared (Ftir) Study Of the Inclusion Com...mentioning

confidence: 99%

Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan

Enggi,

Sulistiawati,

Himawan

et al. 2024

ACS Biomater. Sci. Eng.

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“…After that, the skin was observed with a Leica EZ4 W stereomicroscope at the application location and then harvested by an 8.0 mm diameter biopsy punch (Stiefel, Middlesex, UK). Next, the skin samples were cut into tiny pieces with scissors and homogenized with stainless steel beads by TissueLyserLT (QIAGEN, U.K.) to extract the drug as previously described . The drugs in the skin and in the receiver were quantified by HPLC.…”

Section: Methodsmentioning

confidence: 99%

“…As mentioned previously, conventional topical dosage forms have several drawbacks, limiting the effectiveness of calcipotriol in psoriasis treatment. To address this issue, microneedle patches (MAPs) offer an effective alternative for delivering drugs to the main target. , MAPs are micron-sized (less than 1 mm in length), minimally invasive devices that breach the outermost layer of the skin and the stratum corneum , creating micron-sized pores in the skin and facilitating intradermal delivery of drugs with minimal pain and no bleeding. − Dissolving MAPs are composed of water-soluble polymers that incorporate the drug within the MAPs themselves and dissolve once inserted into the skin. , Dissolving MAPs can achieve controlled drug release due to the dissolution rate of the constituted polymer . In addition, dissolving MAPs often results in favorable biocompatibility and is therefore promising for long-term use. , When poorly soluble drugs are loaded into MAP tips, drug diffusion to the drug-free polymer layer can be prevented, facilitating easy detachment of the tips from the baseplates and reducing the wearing time of the MAPs. , Novel, trilayer MAPs were developed in this study to create a more consumer-friendly product with potentially higher user acceptability.…”

Section: Introductionmentioning

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

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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.

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“…As such, the functionality and molecular weight of both the polymer and cross-linker used in a hydrogel formulation play an important role in cross-linking and, therefore, swelling that, ultimately, influences drug delivery via hydrogel-forming MAPs. 35,36 Considering the hydrogels tested here, the PVA/PVP formulation demonstrated reduced swelling, compared to the Gantrez formulation, due to the higher cross-link density that exists within its polymer network. 20 In the PVA/PVP formulation, cross-linking occurs in the form of esterification between the hydroxy group present on the PVA and carboxylic acid groups present on citric acid.…”

Section: Hydrogel-forming Maps 311 Characterization Of Hydrogel-formi...mentioning

confidence: 99%

Polymeric Microarray Patches for Enhanced Transdermal Delivery of the Poorly Soluble Drug Olanzapine

McKenna,

Abbate,

Vora

et al. 2023

ACS Appl. Mater. Interfaces

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Transdermal drug delivery is an alternative route of administration that offers avoidance of the associated drawbacks of orally and parenterally administered hydrophobics. However, owing to the extremely specific set of physicochemical characteristics required for passive transdermal drug permeation, the development of marketed transdermal products containing poorly soluble drugs has been severely limited. Microarray patches (MAPs) are a type of transdermal patch that differ from the traditional patch design due to the presence of tiny, micron-sized needles that permit enhanced drug permeation on their application surface. To date, MAPs have predominantly been used to deliver hydrophilic compounds. However, this work challenges this trend and focuses on the use of MAPs, in combination with commonly utilized solubility-enhancing techniques, to deliver the hydrophobic drug olanzapine (OLP) across the skin. Specifically, cyclodextrin (CD) complexation and particle size reduction were employed in tandem with hydrogel-forming and dissolving MAPs, respectively. In vivo experimentation using a female Sprague-Dawley rat model confirmed the successful delivery of OLP from hydrogel-forming MAPs (C max = 611.13 ± 153.34 ng/mL, T max = 2 h) and dissolving MAPs (C max = 690.56 ± 161.33 ng/mL, T max = 2 h) in a manner similar to that of oral therapy in terms of the rate and extent of drug absorption, as well as overall drug exposure and bioavailability. This work is the first reported use of polymeric MAPs in combination with the solubility-enhancing techniques of CD complexation and particle size reduction to successfully deliver the poorly soluble drug OLP via the transdermal route. Accordingly, this paper provides significant evidence to support an expansion of the library of molecules amenable to MAP-mediated drug delivery to include those that exhibit poor aqueous solubility.

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Hydrogel-forming microarray patches with cyclodextrin drug reservoirs for long-acting delivery of poorly soluble cabotegravir sodium for HIV Pre-Exposure Prophylaxis

Cited by 45 publications

References 41 publications

Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan

Application of Biomaterials in the Development of Hydrogel-Forming Microneedles Integrated with a Cyclodextrin Drug Reservoir for Improved Pharmacokinetic Profiles of Telmisartan

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

Polymeric Microarray Patches for Enhanced Transdermal Delivery of the Poorly Soluble Drug Olanzapine

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