The terpene-indole alkaloids loaded erythrocytes as a drug carrier: design and assessment

Abstract

The aim of this work was to elucidate the certain parameters (morphological, physicochemical) of terpene-indole alkaloids (TIAs) encapsulated human erythrocytes as a drug delivery system, and in addition to providing insight into the functional state of erythrocytes subjected to extracorporeal saturation with TIAs. Methods -A modified hypotonic pre-swelling method was implemented to obtain TIAs encapsulated erythrocytes. The content of entrapped TIAs in the erythrocytes was evaluated by a validated analytical method. The morphological and physicochemical properties of TIAs encapsulated erythrocytes were assessed by turbidity spectrum method and the osmotic resistance (OR) of encapsulated erythrocytes. Also, a series of in vitro tests have been carried out to characterize the drug release, haemoglobin leakage, and stability under storage condition. Results -TIAs loaded erythrocytes with drug encapsulation efficiency -vincristine sulfate (VCR) 42.963 ± 2.648%, and vinblastine sulfate (VLB) 44.266±2.432% were achieved by a modified pre-swelling hypotonic lysis method. Achieving higher TIAs encapsulation efficiency considerably essential in order to deliver a therapeutic success, however using improved encapsulation techniques have been achieved -VCR: 61.071±2.582% and VLB: 62.425±2.5288%, respectively. In the experiments, it was established, the morphological and physicochemical parameters of the obtained TIAs loaded erythrocytes were varied from the control erythrocytes in the order ~20-30%, although loaded erythrocytes can be stored at +4 0 C for 7 days while the encapsulate drug amount without falling below 95.964±0.472%. Conclusion -The stability and functionality of TIAs loaded erythrocytes were demonstrating relatively good performance with comparison to control erythrocytes and can be suggested to conduct in vivo experiment in animals for evaluating therapeutic potential compared to free drug forms.

Cell-mimicking polyethylene glycol-diacrylate based nanolipogel for encapsulation and delivery of hydrophilic biomolecule

“…Therefore, we established a new method for MLG formation based on loaded erythrocytes as drug carriers ( Jeewantha and Slivkin, 2018 ), to study the diffusion coefficient of encapsulated molecules using FRAP. Briefly, human dermal fibroblasts were lysed and loaded with PEGDA solutions together with Tetramethylrhodamine Isothiocyanate-Dextran (DRITC), then purified for photo-crosslinking and imaged under a laser confocal microscope.…”

“…However, we failed to achieve the MLG based on conventional liposome preparation methods. So we explored the preparation of cell membrane based MLGs by an adapted hypo-osmotic method ( Jeewantha and Slivkin, 2018 ), which was used to harvest the cell membrane ghosts of human dermal fibroblasts and encapsulate PEGDA with DRITC. Briefly, cultured HDFs were collected, washed with PBS and resuspended in .6% NaCl for 30 min at 4°C.…”

Antiviral Properties of Flavonoids and Delivery Strategies

“…This nanoparticle approach paves the way for encapsulating drugs, small molecules, nutraceuticals and other bioactive ingredients to obtain safer cellular uptake, improved biodistribution, specific targeted delivery and enhancement of the therapeutic antiviral efficacy of encapsulated drugs and phytochemicals [ 64 ]. The increase in antiviral efficacy and bioavailability of flavonoids may be attained through their encapsulation into red blood cells (RBCs), as has occurred for other type of antiviral drugs and molecules, such as fludarabine ( Figure 4 ) [ 65 ], vincristine and vinblastine [ 66 , 67 ]. The idea of using RBCs as delivery system for flavonoids takes its advantage from the favorable characteristics of these cells.…”

In vivo nano-biosensing element of red blood cell-mediated delivery

“…In essence, most theranostic agents that are nontoxic to RBCs including novel nanomedicines, peptides, and nucleic acids can be encapsulated into RBCs without damage. One universally used procedure is based on the reversible opening of the pores on the RBC membrane that are large enough (ranging from 10 to 500 nm) to permit the crossing of external agents under low osmotic pressure as shown in Figure 4 (Jeewantha and Slivkin, 2018). This process is able to entrap a large variety of drugs into RBCs uniformly, resulting in final products with good reproducibility, reliability, and viability, thus has been developed into the industrial scale and is widely selected by experts and researchers (Moghimi et al, 2001).…”