A Bilayer Microarray Patch (MAP) for HIV Pre-Exposure Prophylaxis: The Role of MAP Designs and Formulation Composition in Enhancing Long-Acting Drug Delivery

被引:14
作者
Vora, Lalitkumar K. [1 ]
Tekko, Ismaiel A. [1 ]
Zanutto, Fabiana Volpe [1 ]
Sabri, Akmal [1 ]
Choy, Robert K. M. [2 ]
Mistilis, Jessica [2 ]
Kwarteng, Priscilla [2 ]
Jarrahian, Courtney [2 ]
McCarthy, Helen O. [1 ]
Donnelly, Ryan F. [1 ]
机构
[1] Queens Univ Belfast, Med Biol Ctr, Sch Pharm, 97 Lisburn Rd, Belfast BT9 7BL, North Ireland
[2] PATH, 2201 Westlake Ave, Seattle, DC 98121 USA
基金
英国工程与自然科学研究理事会;
关键词
cabotegravir; dissolving microarray patch; microneedles; HIV; long-acting drugs; pre-exposure prophylaxis; intradermal delivery;
D O I
10.3390/pharmaceutics16010142
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Microarray patches (MAPs) have shown great potential for efficient and patient-friendly drug delivery through the skin; however, improving their delivery efficiency for long-acting drug release remains a significant challenge. This research provides an overview of novel strategies aimed at enhancing the efficiency of MAP delivery of micronized cabotegravir sodium (CAB Na) for HIV pre-exposure prophylaxis (PrEP). The refinement of microneedle design parameters, including needle length, shape, density, and arrangement, and the formulation properties, such as solubility, viscosity, polymer molecular weight, and stability, are crucial for improving penetration and release profiles. Additionally, a bilayer MAP optimization step was conducted by diluting the CAB Na polymeric mixture to localize the drug into the tips of the needles to enable rapid drug deposition into the skin following MAP application. Six MAP designs were analyzed and investigated with regard to delivery efficiency into the skin in ex vivo and in vivo studies. The improved MAP design and formulations were found to be robust and had more than 30% in vivo delivery efficiency, with plasma levels several-fold above the therapeutic concentration over a month. Repeated weekly dosing demonstrated the robustness of MAPs in delivering a consistent and sustained dose of CAB. In summary, CAB Na MAPs were able to deliver therapeutically relevant levels of drug.
引用
收藏
页数:21
相关论文
共 41 条
[1]   Soluplus®-based dissolving microarray patches loaded with colchicine: towards a minimally invasive treatment and management of gout [J].
Anjani, Qonita Kurnia ;
Bin Sabri, Akmal Hidayat ;
Moreno-Castellanos, Natalia ;
Utomo, Emilia ;
Carcamo-Martinez, Alvaro ;
Dominguez-Robles, Juan ;
Wardoyo, Luki Ahmadi Hari ;
Donnelly, Ryan F. .
BIOMATERIALS SCIENCE, 2022, 10 (20) :5838-5855
[2]   Metronidazole nanosuspension loaded dissolving microarray patches: An engineered composite pharmaceutical system for the treatment of skin and soft tissue infection [J].
Anjani, Qonita Kurnia ;
Bin Sabri, Akmal Hidayat ;
Dominguez-Robles, Juan ;
Moreno-Castellanos, Natalia ;
Utomo, Emilia ;
Wardoyo, Luki Ahmadi Hari ;
Larraneta, Eneko ;
Donnelly, Ryan F. .
BIOMATERIALS ADVANCES, 2022, 140
[3]   ISOLATION OF A T-LYMPHOTROPIC RETROVIRUS FROM A PATIENT AT RISK FOR ACQUIRED IMMUNE-DEFICIENCY SYNDROME (AIDS) [J].
BARRESINOUSSI, F ;
CHERMANN, JC ;
REY, F ;
NUGEYRE, MT ;
CHAMARET, S ;
GRUEST, J ;
DAUGUET, C ;
AXLERBLIN, C ;
VEZINETBRUN, F ;
ROUZIOUX, C ;
ROZENBAUM, W ;
MONTAGNIER, L .
SCIENCE, 1983, 220 (4599) :868-871
[4]   MEASUREMENT OF INTRACELLULAR PH OF SKELETAL MUSCLE WITH PH-SENSITIVE GLASS MICROELECTRODES [J].
CARTER, NW ;
RECTOR, FC ;
CAMPION, DS ;
SELDIN, DW .
JOURNAL OF CLINICAL INVESTIGATION, 1967, 46 (06) :920-&
[5]   Two-Photon Polymerisation 3D Printing of Microneedle Array Templates with Versatile Designs: Application in the Development of Polymeric Drug Delivery Systems [J].
Cordeiro, Ana Sara ;
Tekko, Ismaiel A. ;
Jomaa, Mohamed H. ;
Vora, Lalitkumar ;
McAlister, Emma ;
Volpe-Zanutto, Fabiana ;
Nethery, Matthew ;
Baine, Paul T. ;
Mitchell, Neil ;
McNeill, David W. ;
Donnelly, Ryan F. .
PHARMACEUTICAL RESEARCH, 2020, 37 (09)
[6]   Optical coherence tomography is a valuable tool in the study of the effects of microneedle geometry on skin penetration characteristics and in-skin dissolution [J].
Donnelly, Ryan F. ;
Garland, Martin J. ;
Morrow, Desmond I. J. ;
Migalska, Katarzyna ;
Singh, Thakur Raghu Raj ;
Majithiya, Rita ;
Woolfson, A. David .
JOURNAL OF CONTROLLED RELEASE, 2010, 147 (03) :333-341
[7]   Global, regional, and national incidence, prevalence, and mortality of HIV, 1980-2017, and forecasts to 2030, for 195 countries and territories: a systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study 2017 [J].
Frank, Tahvi D. ;
Carter, Austin ;
Jahagirdar, Deepa ;
Biehl, Molly H. ;
Douwes-Schultz, Dirk ;
Larson, Samantha Leigh ;
Arora, Megha ;
Dwyer-Lindgren, Laura ;
Steuben, Krista M. ;
Abbastabar, Hedayat ;
Abu-Raddad, Laith Jamal ;
Abyu, Direslgne Misker ;
Adabi, Maryam ;
Adebayo, Oladimeji M. ;
Adekanmbi, Victor ;
Adetokunboh, Olatunji O. ;
Ahmadi, Alireza ;
Ahmadi, Keivan ;
Ahmadian, Elham ;
Ahmadpour, Ehsan ;
Ahmed, Muktar Beshir ;
Akal, Chalachew Genet ;
Alahdab, Fares ;
Alam, Noore ;
Albertson, Samuel B. ;
Alemnew, Birhan Tamene T. ;
Alene, Kefyalew Addis ;
Alipour, Vahid ;
Alvis-Guzman, Nelson ;
Amini, Saeed ;
Anbari, Zohreh ;
Anber, Nahla Hamed ;
Anjomshoa, Mina ;
Antonio, Carl Abelardo T. ;
Arabloo, Jalal ;
Aremu, Olatunde ;
Areri, Habtamu Abera ;
Asfaw, Ephrem Tsegay ;
Ashagre, Alebachew Fasil ;
Asmelash, Daniel ;
Asrat, Anemaw A. ;
Avokpaho, Euripide F. G. A. ;
Awasthi, Ashish ;
Awoke, Nefsu ;
Ayanore, Martin Amogre ;
Azari, Samad ;
Badawi, Alaa ;
Bagherzadeh, Mojtaba ;
Banach, Maciej ;
Barac, Aleksandra .
LANCET HIV, 2019, 6 (12) :E831-E859
[8]   Microarray patch for HIV prevention and as a multipurpose prevention technology to prevent HIV and unplanned pregnancy: an assessment of potential acceptability, usability, and programmatic fit in Kenya [J].
Gachigua, Sammy Gakero ;
Karuga, Robinson ;
Ngunjiri, Anne ;
Jarrahian, Courtney ;
Coffey, Patricia S. ;
Kilbourne-Brook, Maggie ;
Otiso, Lilian .
FRONTIERS IN REPRODUCTIVE HEALTH, 2023, 5
[9]   Trend of HIV/AIDS for the last 26 years and predicting achievement of the 90-90-90 HIV prevention targets by 2020 in Ethiopia: a time series analysis [J].
Girum, Tadele ;
Wasie, Abebaw ;
Worku, Abdulsemed .
BMC INFECTIOUS DISEASES, 2018, 18
[10]  
Gottlieb M.S., 1982, J. Urol., V128, P444, DOI DOI 10.1016/S0022-5347(17)52990-0