“Look deep into nature, and you will understand everything better”: Albert Einstein
Biomimetics is a new era of innovation inspired by nature and utilised for advancement of biological sources, bioengineering and medicine. In pharmaceuticals, the concept is being explored intensively for designing targeted drug delivery systems which are projected to capture the $ 319 billion market worldwide.
The term ‘Biomimetics’ though coined in 1957, has gained popularity only a decade ago with respect to design of smart drug delivery systems. This escalation of interest wherein biomimetics conceptual strategies are assimilated to drug delivery applications in large measure is contributed to popularity of ‘nano’ systems.
Nano carriers have been instrumental to overcome complications due to limited solubility of drug, permeability across membranes and toxicity related issues. However, targeted release of drugs within specific cells is difficult to achieve with basic nano carriers. To convert the magic bullet-dream of Paul Ehrlich into reality so as to achieve target specific and organ/disease specific delivery, biomimetic nano composite would play a crucial role.
Biometric nano composites are those magic bullets in which natural and/or synthetic amino acids, saccharides or lipids are linked to nano carriers by surface modification or arrangement in its geometry to develop unique nano composites (Sheikh pour et al., 2017) which would mimic cellular micro environment. The cell signalling moieties which are used could be inactivated viral or bacterial vectors or synthetic nano particles having properties parallel to biological materials. For therapeutic solicitations though, synthetic nano particles are preferred. An account of currently researched biomimetic - nano composite nano structures is presented below.
Biomimetic hydrogel nanocomposites
Hydrogels fabricated from natural or synthetic biopolymers or their hybrids are widely employed as drug delivery scaffolds due to their biocompatibility, soft tissue like assets and water swollen conduits enabling increased permeability to oxygen, nutrients and water soluble metabolites. Thus, they mimic extracellular microenvironment enabling increased interaction with adjacent cells. To enhance molecular recognition or specific cellular response, hydrogel nano composites may be fabricated to be pH/temperature/enzyme/bookmarker responsive and release of actives from such hydrogel composites could be modulated for fast/pulsatile/controlled release profile. Examples temperature dependent albumin in heterogeneous agarose hydrogels, poly (ethylene glycol) – diacrylate ephrin-1 hydrogels.
Biomimetic micellar nano composites
Micelles are spherical, supra molecular, self-assembled, nano sized colloidal particles with an inner hydrophobic core and an outer hydrophilic corona (shell) designed by the aggregation of amphiphilic molecules or surfactants in an aqueous medium. In the field of the colloidal drug delivery systems, polymeric micelles are common due to their ability of significantly modifying the release profiles of drugs. By using biological moieties or biomimetic base-block copolymers during self-assembly stage of micelles, one can obtain innovative biomimetic amphiphiles in micellar arrangements to provide novel, controllable and highly localized delivery systems. Receptor-mediated uptake is the main focus area in biomimetic micellar and polymeric nano composites in which the encapsulated drug is delivered to target site with the help of a carrier or ligand-based approach. Both systems show a great application in target specific drug delivery in cancer therapy with improved bioavailability and higher cellular uptake. Novel biomimetic nano composites with commercially available amphiphilic polymer Cholesterol terminated PEO (Chol-PEO) have been utilized for Adriamycin, a hydrophobic anti-cancer drug. Others are RGD/TAT micelles, PFO-block-PCL with spermine modification.
Biomimetic liposomes
Liposomes are supra molecular assemblies of amphiphilic lipids, which self-associate to encompass an aqueous core surrounded by a lipid bilayer membrane. Their charge and surface properties can be tuned simply by changing the composition of the phospholipids or by adding new biological components (natural or artificial) to the lipid mixture during the preparation, which makes the system more suited to the active targeting of specific diseases/pathogens/tissues. The amphiphilic domain structure of liposomes enables a variety of biological or therapeutic agents (e.g., nucleic acids, enzymes, proteins, peptide vaccines, anticancer drugs, and imaging agents) to be loaded into this assembly. This arrangement also allows for drug delivery that is pH, temperature and other stimuli dependent, and hence, mimics the actions of biological carriers of a body. Example includes, PEG-coated liposomal nano composite for transferring O2 in red blood cells, artificially. Biomimetic liposomal systems also have a scope in the design of micro reactors and arti?cial cells.
Biometric dendrimers
Dendrimers are three-dimensional polymer molecules with highly branched and regular architectures, that have inner space and functional groups at the periphery, which are suitable for encapsulation and conjugation, respectively. Because of unique physical and chemical properties due to their size ?10nm) and functionality, their application in drug delivery is remarkable.
The inherent globular shape of higher generation dendrimers makes them ideal applicants for macromolecular biomimetics. A number of moieties can be linked to the reactive terminal groups on the surface of dendrimers to produce biomimetic drug carriers for targeted drug delivery. Attaching target specific different bioactive agents, protein or growth factors modifies its architecture and makes them more compatible to deliver drugs to specific target sites. Ongoing research in this field aims to make the system more specific and selective for specific biotechnological applications. Example included FA-PEG-PAMAM dendrimers to release 5-FU within target cells.
One of the key requirement for the formation of biomimetic nano composites is its ability to be amenable to surface topography modifications. Generally, the packing ratio governs the shape of these biomimetic nano composite architectures. Most of the researchers have utilized spherical particles, nano tubes and nanofibers though some reports on irregular shape biomimetic nano particles for higher and specific cellular uptake are also emerging. Overall a lot of research inputs are targeted towards biologically inspired designs (Biomimetics) and these coupled with nano composites may probably challenge the present day paradigm of technology.
Our laboratory at Department of pharmaceutical sciences and technology (www.vbpgroup-ict.in) is currently engaged in utilization of these biomimetic nano composite for delivery of anti-alzheimer, anti-cancer and anti-infective drugs as well as for gene delivery.
We have in-house patented technologies for biomimetic lipid conjugation to yield higher-brain uptake and higher mitochondrial uptake. The technologies for specifically targeted malarial parasites in RBCs and cerebral malaria are available for technology transfer.
Currently, we are also working on translating the concept of biomimetic nanocomposites on drug delivery devices and have confidence that present day technology would witness a paradigm shift for sustainable, green technology.
(Vandana B. Patravale is Professor of Pharmaceutics and Pratik S. Kakade is Senior Research Fellow, Institute of Chemical Technology)