2. Academic Validation
  3. Streptomycin sulphate loaded solid lipid nanoparticles show enhanced uptake in macrophage, lower MIC in Mycobacterium and improved oral bioavailability

Streptomycin sulphate loaded solid lipid nanoparticles show enhanced uptake in macrophage, lower MIC in Mycobacterium and improved oral bioavailability

  • Eur J Pharm Biopharm. 2021 Mar;160:100-124. doi: 10.1016/j.ejpb.2021.01.009.
Mandeep Singh 1,  Nicola Schiavone 2,  Laura Papucci 2,  Prathiba Maan 3,  Jagdeep Kaur 3,  Gurdarshan Singh 4,  Utpal Nandi 4,  Daniele Nosi 5,  Alessia Tani 5,  Gopal K Khuller 6,  Manisha Priya 7,  Ramandeep Singh 7,  Indu Pal Kaur 8
Affiliations

Affiliations

  • 1 University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160014, India.
  • 2 Department of Experimental and Clinical Biomedical Sciences "Mario Serio", Section of Experimental Pathology and Oncology, University of Florence, Italy.
  • 3 Department of Biotechnology, BMS Block-1, Sector 25, Panjab University, Chandigarh 160014, India.
  • 4 PK-PD-Toxicology & Formulation Division, CSIR-Indian Institute of Integrative Medicine, Jammu, India.
  • 5 Department of Experimental and Clinical Medicine, Section of Anatomy and Histology, University of Florence, Florence, Italy.
  • 6 Department of Biochemistry, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
  • 7 Tuberculosis Research Laboratory, Translational Health Science and Technology Institute, NCR Biotech Cluster, PO Box # 4, Faridabad-Gurugram Expressway, Faridabad 121003, India.
  • 8 University Institute of Pharmaceutical Sciences, UGC-Centre of Advanced Study, Panjab University, Chandigarh 160014, India. Electronic address: dripkuips@gmail.com.
PMID: 33497794 DOI: 10.1016/j.ejpb.2021.01.009
Abstract

Present study addresses the challenge of incorporating hydrophilic streptomycin sulphate (STRS; log P -6.4) with high dose (1 g/day) into a lipid matrix of SLNs. Cold high-pressure homogenization technique used for SLN preparation achieved 30% drug loading and 51.17 ± 0.95% entrapment efficiency. Polyethylene glycol 600 as a supporting-surfactant assigned small size (218.1 ± 15.46 nm) and mucus-penetrating property. It was conceived to administer STRS-SLNs orally rather than intramuscularly. STRS-SLNs remained stable on incubation for varying times in SGF or SIF. STRS-SLNs were extensively characterised for microscopic (TEM and AFM), thermal (DSC), diffraction (XRD) and spectroscopic (NMR and FTIR) properties and showed zero-order controlled release. Enhanced (60 times) intracellular uptake was observed in THP-1 and Pgp expressing LoVo and DLD-1 cell lines, using fluorescein-SLNs. Presence of SLNs in LoVo cells was also revealed by TEM studies. STRS-SLNs showed 3 times reduction in MIC against Mycobacterium tuberculosis H37RV (256182) in comparison to free STRS. It also showed better activity against both M. bovis BCG and Mycobacterium tuberculosis H37RV (272994) in comparison to free STRS. Cytotoxicity and acute toxicity studies (OECD 425 guidelines) confirmed in vitro and in vivo safety of STRS-SLNs. Single-dose oral pharmacokinetic studies in rat plasma using validated LCMS/MS technique or the microbioassay showed significant oral absorption and bioavailability (160% - 710% increase than free drug).

Keywords

Cold high pressure homogenization; Controlled release; Hydrophilic molecule; Intracellular uptake; Invitro and invivo toxicity; Oral pharmacokinetic.

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