An effective treatment approach of DPP-IV inhibitor encapsulated polymeric nanoparticles conjugated with anti-CD-4 mAb for type 1 diabetes

• Published in: Drug development and industrial pharmacy 2018-07, Vol.44 (7), p.1120-1129
• Main Authors: Thondawada, Mahesh, Wadhwani, Ashish Devidas, S Palanisamy, Dhanabal, Rathore, Hanumant Singh, Gupta, Ramesh C, Chintamaneni, Pavan Kumar, Samanta, Malay K, Dubala, Anil, Varma, Sameer, Krishnamurthy, Praveen T, Gowthamarajan, Kuppusamy
• Format: Article
• Language: English
• Subjects: Animals; Antibodies - chemistry; CD4 Antigens - chemistry; Cell Line, Tumor; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacology; Diabetes Mellitus, Type 1 - drug therapy; Dipeptidyl Peptidase 4 - metabolism; Dipeptidyl-Peptidase IV Inhibitors - chemistry; Dipeptidyl-Peptidase IV Inhibitors - pharmacology; Drug Carriers - chemistry; Drug Delivery Systems - methods; Hypoglycemic Agents - chemistry; Hypoglycemic Agents - pharmacology; Lactic Acid - chemistry; Nanoparticles - chemistry; Particle Size; Polyglycolic Acid - chemistry; Polymers - chemistry; Rats
• ISSN: 0363-9045; 1520-5762
• DOI: 10.1080/03639045.2018.1438460

Nanotechnology based biomedical approaches and surface modification techniques made it easier for targeting specific site and improving the treatment efficacy. The present study reports on targeted polymeric nanoparticles conjugated with antibody as a site-specific carrier system for effective treatment of type 1 diabetes. Sitagliptin (SP)-loaded Poly (lactic-co-glycolic acid) (PLGA) nanoparticles (NP) were prepared by nanoprecipitation cum solvent evaporation method and were characterized in terms of morphology, size, surface charge, and entrapment efficiency. Optimized batch demonstrated a particle size of 105.24 nm, with significant entrapment efficacy. In vitro release studies exhibited a controlled release pattern of 67.76 ± 1.30% in 24 h, and a maximum of 96.59 ± 1.26% at the end of 48 h. Thiol groups were introduced on the surface of SP-NPs whose concentration on SP-NPs was 27 ± 2.6 mmol/mol PLGA-NPs, anti-CD4 antibody clone Q4120 was conjugated to the thiolated SP-NPs via a sulfo-MBS cross-linker, ∼70% conjugation was observed. The in vitro cytotoxicity studies performed on RIN-5 F cells for mAb-SP-NPs presented an IC of 76 µg/mL, and the insulin release assay had revealed an increased release at 5.15 ± 0.16 IU/mL. The results indicate that mAb-SP-NPs allowed a controlled release of SP and thereby produced insulin levels comparable with control. Therefore, mAb-SP-NPs system appears to be effective in the treatment of auto immune diabetes, subject to further analysis.