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Complex dosing regimens, costs, side effects, biodistribution limitations, and variable drug pharmacokinetic patterns have affected the long-term efficacy of antiretroviral medicines. To address these problems, a nanoparticle indinavir (NP-IDV) formulation packaged into carrier bone marrow-derived macrophages (BMMs) was developed. Drug distribution and disease outcomes were assessed in immune-competent and human immunodeficiency virus type 1 (HIV-1)-infected humanized immune-deficient mice, respectively. In the former, NP-IDV formulation contained within BMMs was adoptively transferred. After a single administration, single-photon emission computed tomography, histology, and reverse-phase-high-performance liquid chromatography (RP-HPLC) demonstrated robust lung, liver, and spleen BMMs and drug distribution. Tissue and sera IDV levels were greater than or equal to 50 microM for 2 weeks. NP-IDV-BMMs administered to HIV-1-challenged humanized mice revealed reduced numbers of virus-infected cells in plasma, lymph nodes, spleen, liver, and lung, as well as, CD4(+) T-cell protection. We conclude that a single dose of NP-IDV, using BMMs as a carrier, is effective and warrants consideration for human testing.

Titel:	Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery.
Autor/in / Beteiligte Person:	Dou, H ; Destache, CJ ; Morehead, JR ; Mosley, RL ; Boska, MD ; Kingsley, J ; Gorantla, S ; Poluektova, L ; Nelson, JA ; Chaubal, M ; Werling, J ; Kipp, J ; Rabinow, BE ; Gendelman, HE
Zeitschrift:	Blood, Jg. 108 (2006-10-15), Heft 8, S. 2827
Veröffentlichung:	2021- : [New York] : Elsevier ; <i>Original Publication</i>: New York, Grune & Stratton [etc.], 2006
Medientyp:	academicJournal
ISSN:	0006-4971 (print)
DOI:	10.1182/blood-2006-03-012534
Schlagwort:	Animals Chemistry, Pharmaceutical Disease Models, Animal HIV Infections drug therapy HIV Infections immunology HIV Infections metabolism HIV Protease Inhibitors blood HIV Protease Inhibitors pharmacokinetics HIV-1 Humans Indinavir blood Indinavir pharmacokinetics Macrophages transplantation Macrophages ultrastructure Male Mice Mice, Inbred BALB C Mice, Inbred NOD Mice, SCID Microscopy, Electron, Scanning Nanotechnology Tissue Distribution Drug Delivery Systems HIV Protease Inhibitors administration & dosage Indinavir administration & dosage Macrophages metabolism Nanostructures
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Language: English [Blood] 2006 Oct 15; Vol. 108 (8), pp. 2827-35. <i>Date of Electronic Publication: </i>2006 Jun 29. MeSH Terms: Drug Delivery Systems* ; Nanostructures* ; HIV Protease Inhibitors / administration & dosage ; Indinavir / administration & dosage ; Macrophages / *metabolism ; Animals ; Chemistry, Pharmaceutical ; Disease Models, Animal ; HIV Infections / drug therapy ; HIV Infections / immunology ; HIV Infections / metabolism ; HIV Protease Inhibitors / blood ; HIV Protease Inhibitors / pharmacokinetics ; HIV-1 ; Humans ; Indinavir / blood ; Indinavir / pharmacokinetics ; Macrophages / transplantation ; Macrophages / ultrastructure ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, SCID ; Microscopy, Electron, Scanning ; Nanotechnology ; Tissue Distribution Comments: Erratum in: Blood. 2007 Mar 1;109(5):1816. References: Eur J Pharm Sci. 2001 Feb;12(4):471-8. (PMID: 11231114) ; Mod Pathol. 2005 Jan;18(1):127-36. (PMID: 15389256) ; AIDS. 2001 May 4;15(7):941-3. (PMID: 11399971) ; AIDS. 2001 Sep 7;15(13):1701-6. (PMID: 11546946) ; Lancet. 2001 Oct 20;358(9290):1322-7. (PMID: 11684213) ; Curr HIV Res. 2005 Jan;3(1):31-41. (PMID: 15638721) ; Nutrition. 2005 Jan;21(1):96-9. (PMID: 15661483) ; J Virol. 2005 Feb;79(4):2124-32. (PMID: 15681415) ; J Microbiol Immunol Infect. 2005 Feb;38(1):31-4. (PMID: 15692624) ; Crit Rev Ther Drug Carrier Syst. 2004;21(5):387-422. (PMID: 15719481) ; Trends Pharmacol Sci. 2005 May;26(5):258-64. (PMID: 15860373) ; J Neurovirol. 2005;11 Suppl 1:76-80. (PMID: 15960241) ; Curr Med Chem. 2005;12(15):1705-19. (PMID: 16029143) ; Technol Cancer Res Treat. 2005 Aug;4(4):407-16. (PMID: 16029059) ; Int J Pharm. 2005 Sep 14;301(1-2):268-76. (PMID: 16023808) ; J Med Virol. 2005 Nov;77(3):345-50. (PMID: 16173015) ; Drug Discov Today. 2005 Nov 1;10(21):1435-42. (PMID: 16243263) ; J Nanosci Nanotechnol. 2005 Oct;5(10):1688-93. (PMID: 16245529) ; Langmuir. 2005 Nov 8;21(23):10644-54. (PMID: 16262332) ; Technol Cancer Res Treat. 2005 Dec;4(6):645-50. (PMID: 16292884) ; Expert Opin Drug Deliv. 2004 Nov;1(1):181-4. (PMID: 16296729) ; J Acquir Immune Defic Syndr. 2006 Jan 1;41(1):23-30. (PMID: 16340469) ; Biol Blood Marrow Transplant. 2006 Jan;12(1 Suppl 1):87-91. (PMID: 16399591) ; AIDS Patient Care STDS. 2006 Jan;20(1):6-18. (PMID: 16426151) ; J Gen Virol. 2006 May;87(Pt 5):1303-9. (PMID: 16603533) ; Virology. 2007 Feb 5;358(1):148-58. (PMID: 16997345) ; Nature. 2001 Apr 19;410(6831):968-73. (PMID: 11309626) ; Anticancer Drugs. 2000 Jun;11(5):369-76. (PMID: 10912953) ; Circulation. 2002 Jan 15;105(2):230-5. (PMID: 11790706) ; Infection. 2002 Jan;30(1):13-6. (PMID: 11876509) ; Pharm Res. 2002 Feb;19(2):132-9. (PMID: 11883639) ; J Immunol. 2002 Apr 15;168(8):3941-9. (PMID: 11937550) ; Crit Rev Ther Drug Carrier Syst. 2002;19(1):1-72. (PMID: 12046891) ; Int J Pharm. 2002 Jun 4;239(1-2):113-20. (PMID: 12052696) ; Drug Dev Ind Pharm. 2002 Jul;28(6):621-30. (PMID: 12149954) ; AIDS Res Hum Retroviruses. 2002 Sep 1;18(13):909-16. (PMID: 12230934) ; J Pharm Sci. 2003 May;92(5):1085-94. (PMID: 12712429) ; Tuberculosis (Edinb). 2003;83(6):373-8. (PMID: 14623168) ; Crit Rev Ther Drug Carrier Syst. 2003;20(5):357-403. (PMID: 14959789) ; Curr Med Chem. 2004 Feb;11(4):413-24. (PMID: 14965222) ; J Immunol. 2004 Jun 15;172(12):7610-7. (PMID: 15187141) ; HIV Med. 2004 Jul;5(4):307-13. (PMID: 15236622) ; Antimicrob Agents Chemother. 2004 Nov;48(11):4200-8. (PMID: 15504842) ; AIDS. 1996 May;10(5):485-92. (PMID: 8724039) ; Antimicrob Agents Chemother. 1996 Nov;40(11):2535-41. (PMID: 8913459) ; J Virol. 1997 Sep;71(9):6662-70. (PMID: 9261388) ; Lancet. 1998 Aug 15;352(9127):577-8. (PMID: 9716089) ; J Infect Dis. 1998 Nov;178(5):1299-305. (PMID: 9780249) ; AIDS. 1999 Feb 4;13(2):249-55. (PMID: 10202831) Grant Information: 2R37 NS 36126 United States NS NINDS NIH HHS; P01 NS043985 United States NS NINDS NIH HHS; P20 RR 15635 United States RR NCRR NIH HHS; P01 NS031492 United States NS NINDS NIH HHS; P01 MH 64570 United States MH NIMH NIH HHS; 2R01 NS 034239 United States NS NINDS NIH HHS; P01 NS 31492 United States NS NINDS NIH HHS; P01 MH064570 United States MH NIMH NIH HHS; R37 NS036126 United States NS NINDS NIH HHS; P20 RR015635 United States RR NCRR NIH HHS; R01 NS034239 United States NS NINDS NIH HHS; P01 NS 43985 United States NS NINDS NIH HHS Substance Nomenclature: 0 (HIV Protease Inhibitors) ; 5W6YA9PKKH (Indinavir) Entry Date(s): Date Created: 20060701 Date Completed: 20061102 Latest Revision: 20220410 Update Code: 20240513 PubMed Central ID: PMC1895582

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Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery.