Self-assembly of β-alanine homotetramer: formation of nanovesicles for drug delivery

Abstract

The present paper describes the fabrication of nanovesicles using the stirring induced self-assembly of a b-alanine homotetramer (H 2 N-bAla-bAla-bAla-bAla-CONH 2 ) in an aqueous medium. Dynamic light scattering (DLS) studies revealed the formation of nanostructures with an average particle size of B463 nm. The morphology and size of the nanostructures was also confirmed by electron microscopy. The formation of well-defined spherical nanovesicles in the size range of B100 nm to 250 nm is displayed. Secondary structure estimations using circular dichroism (CD) and infrared spectroscopic (IR) studies suggest an intramolecularly hydrogen bonded conformation for the tetrapeptide. CD and IR studies conducted in an aqueous medium before and after self-assembly depict a significant change in structure and hydrogen bonding patterns. Supportive evidence regarding the conformation of the tetrapeptide is provided by the conformational search using computational methods. The theoretically predicted minimum energy structure depicts an 8-helix type of backbone folding with the formation of two 8-membered intramolecularly hydrogen bonded rings. Four of the short helical type strands of the tetrapeptide were then subjected to a geometry optimization that resulted in the formation of an assembly with a central cavity, completely in agreement with experimental findings. Finally these nanovesicles were evaluated for their potential use as carriers of the potent anti-Parkinson's drug L-DOPA. We have observed that in aqueous media these nanovesicles are able to encapsulate the L-DOPA molecules, indicated by DLS measurements and also by absorption and emission spectroscopic methods. By lowering the pH to 6.2 these loaded vesicles are able to release the drug slowly. These assemblies thus can be considered as potential delivery vehicles for L-DOPA which normally suffers from poor administration.

Self-Assembling Hydrogel Structures for Neural Tissue Repair

“…RAD16-I was employed to create cell-encapsulating microgel beads, which were able to support cell proliferation and diffusion of nutrients . Indeed, other signaling proteins and drugs such as neurotransmitters, gene vectors, and signaling molecules can be encapsulated into the SAP structure for self-assembling, resulting in delivery profiles similar to GF delivery. ,,,− The MAX8 β-hairpin SAP designed by Branco et al exploits the positive charge of the hydrogel network to bind and release negatively charged molecules with different isoelectric points. Koutsopoulos et al investigated the delivery properties of RADA16 with different proteins physically encapsulated during the self-assembling process.…”

Polyaspartic acid, 2-acrylamido-2-Methyl propane sulfonic acid and sodium alginate based biocompatible stimuli responsive polymer gel for controlled release of GHK-Cu peptide for wound healing

“…Zero order, First order, Korsmeyer peppas and Higuchi. 39,40 Different polymers follow different kinetics for releasing the peptide. Detailed explanations of all models are given in Supplementary Material (S5)…”

Ultrashort Peptide Self-Assembly: Front-Runners to Transport Drug and Gene Cargos

“…Amphiphilic peptides have brought a paradigm shift toward self-assembled PA in drug delivery. The amphiphilic peptides provide a lot of option in both linear and cyclic peptide sequences, side chains loaded with charges, self-assembled as vesicles, micelles, nanofibers and nanotubes for delivery systems and for other biotechnological applications (Goel et al, 2015). An account on the versatility of cyclic peptides and the safety measures in terms of size control, length and bundle width of nanotubes during the successful delivery of active pharmaceutical ingredients has been presented in a mini-review by Hsieh and Liaw (2019).…”

“…Though the role of self-assembled peptides in drug and gene delivery is blossoming and there is a substantial flow in the research and review articles as mentioned above, but the short peptides (di-and tri-peptides) appear more promising and game changers, due to their simple structure, cost-effectiveness, nontoxic/non-antigenic nature and superior biocompatibility with enhanced bioactivity (Panda and Chauhan, 2014;Goel et al, 2015;Alam et al, 2016;Guo C. et al, 2016;Habibi et al, 2016;Hamley, 2017;Mishra and Jyoti Panda, 2019;Ni and Zhuo, 2019). Furthermore, the low molecular weight of short peptides allows purification via simple HPLC techniques.…”