Preparation and characterization of anti-HIV nanodrug targeted to microfold cell of gut-associated lymphoid tissue
نویسندگان
چکیده
The human immunodeficiency virus 1 (HIV-1) still remains one of the leading life-threatening diseases in the world. The introduction of highly active antiretroviral therapy has significantly reduced disease morbidity and mortality. However, most of the drugs have variable penetrance into viral reservoir sites, including gut-associated lymphoid tissue (GALT). Being the largest lymphoid organ, GALT plays a key role in early HIV infection and host-pathogen interaction. Many different treatment options have been proposed to eradicate the virus from GALT. However, it becomes difficult to deliver traditional drugs to the GALT because of its complex physiology. In this regard, we developed a polymer-based Pluronic nanocarrier containing anti-HIV drug called efavirenz (EFV) targeting Microfold cells (M-cells) in the GALT. M-cells are specialized epithelial cells that are predominantly present in the GALT. In this work, we have exploited this paracellular transport property of M-cells for targeted delivery of Pluronic nanocarrier tagged EFV, bioconjugated with anti-M-cell-specific antibodies to the GALT (nanodrug). Preliminary characterization showed that the nanodrug (EFV-F12-COOH) is of 140 nm size with 0.3 polydispersion index, and the zeta potential of the particles was -19.38±2.2 mV. Further, drug dissolution study has shown a significantly improved sustained release over free drugs. Binding potential of nanodrug with M-cell was also confirmed with fluorescence microscopy and in vitro uptake and release studies. The anti-HIV activity of the nanodrug was also significantly higher compared to that of free drug. This novel formulation was able to show sustained release of EFV and inhibit the HIV-1 infection in the GALT compared to the free drug. The present study has potential for our in vivo targeted nanodrug delivery system by combining traditional enteric-coated capsule technique via oral administration.
منابع مشابه
Comparative immunohistochemistry of Gut-associated lymphoid tissue (GALT) of, Huso huso in two warm and cold seasons
Abstract The main objective of recent study was comparative immunohistochemistry of Gut-associated lymphoid tissue (GALT) of, Huso huso in two warm and cold seasons. Ten specimens were collected from sturgeon breeding centers and after anesthesia, biometric was taken on them. 0.5 centimeter samples of primary, middle and end of intestine were removed and immediately were placed in Bouin soluti...
متن کاملCharacterization of HIV-1-specific cytotoxic T lymphocytes expressing the mucosal lymphocyte integrin CD103 in rectal and duodenal lymphoid tissue of HIV-1-infected subjects.
Acute HIV-1 infection depletes CD4(+) T cells in gut-associated lymphoid tissue (GALT). The failure of containment of local viral replication, and consequent CD4(+) T cell depletion, might be due to delayed mobilization of effector CD8(+) T cells or absence of functioning HIV-1-specific CD8(+) T cell effectors within GALT. No studies have addressed human intestinal HIV-1-specific CD8(+) T cell ...
متن کاملProduction and Evaluation of Specific Single-Chain Antibodies against CTLA-4 for Cancer-Targeted Therapy
Background: Cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-4 inhibits the growth of malignant tumor cells. Anti-CTLA-4 monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodi...
متن کاملGastrointestinal Viral Load and Enteroendocrine Cell Number Are Associated with Altered Survival in HIV-1 Infected Individuals
Human immunodeficiency virus type 1 (HIV-1) infects and destroys cells of the immune system leading to an overt immune deficiency known as HIV acquired immunodeficiency syndrome (HIV/AIDS). The gut associated lymphoid tissue is one of the major lymphoid tissues targeted by HIV-1, and is considered a reservoir for HIV-1 replication and of major importance in CD4+ T-cell depletion. In addition to...
متن کاملSiglec-F is a novel intestinal M cell marker
Intestinal microfold (M) cells are epithelial cells primarily present on Peyer's patches (PPs) in the small intestine. The ability of M cells to shuttle antigens into the PP for appropriate immune responses makes M cells a target for next-generation oral vaccine delivery. In this regard, discovery of M cell-specific receptors are of great interest, which could act as molecular tags for targeted...
متن کامل