Anabolic Peptide-Enriched Stealth Nanoliposomes for Effective Anti-Osteoporotic Therapy

Abstract

The objective of the present work was to develop PTH (1-34)-loaded stealth nanoliposomes (PTH-LPs) by employing the use of the Quality by Design (QbD) approach. Risk identification was carried out using the Ishikawa fishbone diagram. PTH-LPs were optimized using Box Behnken Design, a type of response surface methodology to examine the effect of independent variables on dependent variables such as particle size and percentage entrapment efficiency (%EE). Design space was generated for PTH-LPs to reduce interbatch variability during the formulation development process. Furthermore, a cytotoxicity assay, cell proliferation assay, calcium calorimetric assay, mineralized nodule formation, and cellular uptake assay were carried out on MG-63 osteoblast-like cells. The results obtained from these procedures demonstrated that lipid concentration had a significant positive impact on particle size and %EE, whereas cholesterol concentration showed a reduction in %EE. The particle size and %EE of optimized formulation were found to be 147.76 ± 2.14 nm and 69.18 ± 3.62%, respectively. Optimized PTH-LPs showed the sustained release profile of the drug. In vitro cell evaluation studies showed PTH-LPs have good biocompatibility with MG-63 cells. The cell proliferation study revealed that PTH-LPs induced osteoblast differentiation which improved the formation of mineralized nodules in MG-63 cells. The outcome of the present study conclusively demonstrated the potential of the QbD concept to build quality in PTH-LPs with improved osteoanabolic therapy in osteoporosis.

Peptide Engraftment on PEGylated Nanoliposomes for Bone Specific Delivery of PTH (1-34) in Osteoporosis

“…SDSSD-LPs were fabricated using the ethanol injection method as per our previous method with a slight modification [ 34 ]. Briefly, the organic phase was made by dissolving HSPC, cholesterol, DSPE-PEG2000, and SDSSD-DSPE in absolute ethanol and injected into 3 mL of acetate buffer containing PTH (1-34) with continuous stirring on a magnetic stirrer at 500 RPM.…”

“…The selection of independent variables, such as material attributes and process parameters, for the statistical optimization of SDSSD-LPs was carried out using a literature review and prior experimentation. Based on our previous experiment of screening design [ 35 ], optimization of non-pegylated [ 36 ] and pegylated nanoliposomes [ 34 ], drug concentration, lipid concentration, and cholesterol concentration were chosen as independent factors, while the dependent variables for the optimization of SDSSD-LPs were particle size and % entrapment efficiency (% EE) by following the response surface method (RSM).…”

Construction Strategy of Functionalized Liposomes and Multidimensional Application

“…By incorporating nucleic acid drugs into the water compartment of liposomes, nucleic acid drugs can be effectively protected from nuclease‐mediated degradation which improves cell uptake efficiency. [ 47 ] Han et al. [ 2c ] encapsulated siRNA in an aqueous core of anionic liposomes prepared with inorganic solvents by thin‐film hydration.…”

Collagen-Based Hydrogels for the Eye: A Comprehensive Review

“…In addition, the administration of a biodegradable matrix, including nanoparticles loaded with a potent drug, to the corneal surface has been found to be an appropriate option for treating inflammatory cases and for preventing postoperative infection in patients. Liposomes are termed a versatile drug delivery system [ 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 ]. Chang et al developed liposomes loaded with moxifloxacin (MFX) and dexamethasone (DEX) and mixed them with hydrogel-forming biodegradable materials (collagen/gelatin/alginate), i.e., CGA-Lipo-MFX/DEX, for prolonged ocular delivery [ 124 ] ( Figure 6 ).…”