Abstract
Background: Tuberculosis is a major public health problem in the world. Isoniazid is a first line antitubercular drug active against Mycobacterium species which inhibits mycolic acid synthesis.
Objective: The aim of the present investigation was the preparation of solid lipid nanoparticle containing Isoniazid to increase bioavailability, sustained release and decrease toxicity by increasing permeability. Methods: Isoniazid was incorporated into SLN for sustained drug delivery, increasing permeability and bioavailability. SLNs were prepared by emulsification followed by the solvent evaporation technique by optimizing lipid, polymer and surfactant ratio under controlled optimized process variables i.e. temperature and stirring speed. SLNs were characterized for particle size analysis, comparative study design in different physiological pH for in-vitro drug release and drug release kinetics. Results: The best in-vitro release for F7 was found to be 80.2% in pH-7.4 and 82.2% in pH-4.5. The particle size of the F7 formulation was found to be in the range of 200- 600nm . Among all 3 optimized formulations, i.e. F3, F7 and F8 in both the pH, F3 followed non-fickian diffusion mechanism in pH-4.5 whereas all the formulations in both pH followed super-case II diffusion mechanism. The stability studies were carried out as per ICH guidelines which signify that the SLNs were found stable in the refrigerated condition. Conclusion: The results clearly demonstrated that SLNs drug delivery system is a promising approach for antitubercular drug delivery as it proved to sustained release, increase permeability, enhanced bioavailability and thus decreased dosing frequency. Kinetic modelling of the formulation with zero, first order, Higuchi and Korsmeyer- peppas is explained in this article.Keywords: In-vitro release, isoniazid, macrophage, nanoparticle, solid lipid nanoparticles, drug delivery.
Graphical Abstract
[1]
Chetty S, Muthusamy R, Ashona SP, Mahmoud ES. Soliman. Recent advancements in the development of anti-tuberculosis drugs. Bioorg Med Chem Lett 2017; 27: 370-86.
[2]
Langer R. Biomaterials in drug delivery and tissue engineering: One laboratory’s experiences. Acc Chem Res 2000; 33: 94-101.
[3]
Diana PG, Vasco F, Lídia MD, et al. Rifabutin-loaded solid lipid nanoparticles for inhaled antitubercular therapy: Physicochemical and in vitro studies. Int J Pharm 2016; 497: 199-209.
[4]
Fang YJ, Lin CH, Chen CH, Lin ZC. Recent advances in the oral delivery of drugs and bioactive natural products using solid lipid nanoparticles as the carriers. J Food Drug Anal 2017; 25: 219-34.
[5]
Sharma PH, Nikam S, Chavan M. Solid lipid nanoparticles: a lipid-based drug delivery. Innov Pharm Pharmacotherapy 2014; 2: 365-76.
[6]
Sathali HAA, Ekambaram P, Priyanka K. Solid lipid nanoparticles: A Review. Sci Revs Chem Commun 2011; 2: 80-102.
[7]
Iyer R, Hsia CCW, Nguyen KT. Nano-therapeutics for the lung: state-of-the-art and future perspectives. Curr Pharm Des 2015; 21: 5233-44.
[8]
Cao P, Bae Y. Polymer nanoparticulate drug delivery and combination cancer therapy. Future Oncol 2012; 8: 1471-80.
[9]
Prabhakar RA, Munusamy MA, Sadasivuni KK, Rajan M. Targeted delivery of rifampicin to tuberculosis-infected macrophages: design, in-vitro, and in-vivo performance of rifampicin-loaded poly (ester amide) s nanocarriers. Int J Pharm 2016; 513: 628-35.
[10]
Paranjpe M, Goymann CCM. Nanoparticle-mediated pulmonary drug delivery: a review. Int J Mol Sci 2014; 15: 5852-73.
[11]
Muller RH, Keck CM. Challenges and solutions for the delivery of biotech drugs: a review of drug nanocrystal technology and lipid nanoparticles. J Biotechnol 2004; 113: 151-70.
[12]
Pillay V, Toit LC, Danckwerts MP. Tuberculosis chemotherapy: current drug delivery approaches. Respir Res 2006; 7: 118.
[14]
Ratnaparkhi MP, Gupta JP. Sustained release oral drug delivery system-An overview. Int J Pharma Res Review 2013; 2: 11-21.
[15]
Lannuccelli V, Maretti E, Rossi T, et al. Inhaled Solid lipid macroparticles to target alveolar macrophages for tuberculosis. Int J Pharm 2014; 462: 74-82.
[16]
Yeo Y, Pei Y. Drug delivery to macrophages: Challenges and opportunities. J Control Release 2016; 240: 202-11.
[17]
Marques MR, Loebenberg R, Almukainzi M. Simulated biological fluids with possible application in dissolution testing. Disso Tech 2011; 18: 15-28.
[18]
Pooja D, Sistla R. Optimization of solid lipid nanoparticles prepared by a single emulsification- solvent evaporation method. Data Brief 2016; 6: 15-9.
[19]
Yadav PSG, Irchhaiya R, Mahor A, Alok S. Development and characterization of solid lipid nanoparticles by solvent diffusion and evaporation method for topical delivery. Int J Pharm Sci Res 2014; 5: 1028-34.
[20]
Parikh R, Dalwadi S. Preparation and characterization of controlled release poly-ɛ caprolactone microparticles of isoniazid for drug delivery through the pulmonary route. Powder Technol 2014; 158-65.
[21]
Dhandaniya TM, Sharma OP, Gohel MC, Mehta P. Current approaches for in vitro drug release study of long-acting parental formulations. Curr Drug Deliv 2015; 1213: 256-70.
Article Metrics
39
3