NDLI: Screening for Potential Adjuvants Administered by the Pulmonary Route for Tuberculosis Vaccines

Content Provider	Springer Nature Link
Author	Wang, Chenchen Muttil, Pavan Lu, Dongmei Beltran Torres, Adela Ayulia Garcia Contreras, Lucila Hickey, Anthony J.
Copyright Year	2009
Abstract	Tuberculosis (TB) infects one third of the world’s population, and new infections occur at a rate of 1/s. Better vaccines are needed than the live mycobacterium Bacille Calmette-Guérin (BCG). Alveolar macrophages (AMΦs) play a central role in pulmonary manifestations of TB. Targeting immunomodulators to AMΦs, the first line of defense against Mycobacterium tuberculosis (Mtb), may initiate a potent cell-mediated immune response. Muramyl dipeptide (MDP) and trehalose dibehenate (TDB) have elicited strong immune response when delivered to the lungs as aerosols. AMΦs show toxicity in response to some immunomodulators. The objective of this work was to screen the immunomodulators MDP and/or TDB encapsulated in microparticles (MPs) and to evaluate certain indicators of toxicity in human AMΦ-like cells. Poly(lactide-co-glycolide) (PLGA) MPs containing MDP and/or TDB were prepared by spray-drying. The morphology, particle size distribution, and immunomodulator encapsulation efficiency of MPs were examined. THP-1 cells were exposed to these MPs for 24 h and characteristics of cell morphology, tumor necrosis factor-alpha (TNF-α) release, lactate dehydrogenase (LDH), N-acetyl-β-d-glucosaminidase (NAG) and alkaline phosphatase (ALP) activity in AMΦ culture supernatants were measured. MTT assay was used to assess the viability of cells. Spray-drying produced low-density MPs having volume median diameters between 4 and 6 μm as measured by laser diffraction and projected area diameter between 3 and 5 μm calculated by microscopy. More TNF-α was produced by THP-1 cells exposed to MPs composed of PLGA-MDP or PLGA alone than PLGA-TDB. LDH release following exposure to MPs of PLGA-MDP and PLGA alone was greater than controls. NAG release was higher following exposure to MPs of PLGA alone or PLGA-MDP 0.1% than PLGA-TDB (0.1% and 1.0%). Cells remained viable after exposure to MPs as per MTT assay. PLGA-MDP MPs demonstrated statistically elevated indicators of biochemical responses in cell culture compared to PLGA-TDB MPs, but the extent of their potential to elicit adverse effects in vivo must be studied independently.
Starting Page	139
Ending Page	147
Page Count	9
File Format	PDF
ISSN	12341234
Journal	The AAPS Journal
Volume Number	11
Issue Number	1
e-ISSN	15507416
Language	English
Publisher	Springer US
Publisher Date	2009-03-10
Publisher Institution	American Association of Pharmaceutical Scientists
Publisher Place	Boston
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	adjuvants cytotoxicity immunostimulant microparticles pulmonary Pharmacy Biotechnology Biochemistry Pharmacology/Toxicology
Content Type	Text
Resource Type	Article

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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