Womens College of Pharmacy Peth-Vadgaon, Kolhapur.
As a type of lipid-based nanocarrier, nanocochleates have demonstrated great promise in improving drug delivery. They are made up of lipid bilayers that are rolled up into a cochleate structure, which provides a unique platform for encapsulating drugs. It has been demonstrated that nanocochleates improve drug stability, target specific tissues or cells, and provide controlled release of drugs. Because of their lipid-based composition, which makes them biocompatible and biodegradable, the use of nanocochleates for drug delivery has several benefits, such as increased efficacy, decreased side effects, and improved bioavailability. Drugs can be delivered precisely and with less damage to healthy tissues thanks to nanocochleates that are made to target particular tissues or cells. Additionally, sustained therapy over an extended length of time can be provided via the controlled release of medications from nanocochleates, which can improve patient outcomes and compliance. Applications for nanocochleates could be found in a number of areas, including as vaccine development, gene transfer, and cancer treatment. To completely grasp the potential of nanocochleates and to maximize their usefulness and design, more research is required. Nonetheless, the information that is now available indicates that nanocochleates hold promise as a means of enhancing medication delivery and curing a variety of illnesses.
In the current situation, biotechnological advancements have produced over 50% of newly discovered drugs. As biotechnology advances, more and more biological therapies are becoming available [1]. In the field of medication delivery, carriers or delivery systems that promote intestinal absorption of these molecules are of great interest. Additionally, changes to the structure of pharmacological compounds are frequently necessary to promote the absorption of medication molecules mediated via receptors. This could change the medication molecule's pharmacological action. Consequently, the necessity to create a medicine delivery system is growing. This might help the medications diffuse across the gut barrier [4]. Liposomes and other lipid-based delivery technologies have drawn a lot of scientific attention. The foundation of the nanocochleate drug delivery system is the encapsulation of medications in a lipid crystal matrix with several layers (a cochleate).in order to possibly distribute the medication in a safe and efficient manner [3]. A sequence of lipid bilayers makes up the cylindrical microstructures known as nanocochleates [6]. Phospholipid cations are stable nanocochleate delivery carriers. Precipitates made of basic, naturally occurring substances, typically calcium and phosphatidylserine [7]. Their structure is complex and distinctive. Made up of a solid lipid bilayer layer, stacked sheets or spirally wrapped up with minimal or no aqueous space inside [3]. This structure shields related "encochleated" molecules against deterioration. Due to the fact that the whole In nanocochleate, the structure is an arrangement multiple layers of solids. Additionally, parts which are contained inside that the nanochleate structure is still intact even though the nanochleate's exterior layers could be exposed to enzymes or harsh environmental conditions [7]. Since the surfaces of nanochleates are both hydrophilic and hydrophobic, they has the ability to encapsulate both hydrophobic medications. Like clofazimine and amphotericin B With amphipathic medications such as doxorubicin [6].
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Figure 1: Nanocochleates
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Figure. 2: Structure of Nanocochleate
Liposomes
Distribution methods based on vesicles, especially liposomes were particularly effective at delivering medications through the membrane, due to the fact that they resemble the cell membrane in structure [2]. The spherical vesicles are called liposome composed of phospholipids with amphiphilia. Hydropholipids can encapsulate both hydrophilic and medications that are hydrophobic and have the ability to self-assemble [11]. Liposomes are increasingly being used to carry medications across membranes. Liposome is a term that is frequently used to denote Water-lipid mesomorphic structures composed of chemical constituents For example, lipids and/or phospholipids [14]. Two Greek terms served as the basis for the word liposome: Lipo signifies "fat," whereas soma means "body."[2]
Mechanism Of Vesicle Formation
Incorporating the lipid phase into the aqueous phase. It interacts hydrophobically to produce bilayers. Or the hydrophilic relationship between lipids or molecules of lipid and water. These lipid layers are generated and then positioned as vesicles using outside energy, like sonication, freezing, heating, and homogenizing [11].
Discovery Of Nanocochlets
The discovery of cochleates occurred during 1975 through The physician D. Papahadjoupoulos and associates and were employed during the 1980s along with1990s to convey Both peptides and antigens for the administration of vaccines. The first nanocochleates appeared in 1999 to produce more uniform but smaller particles [1]. Which have particles smaller than 100 nanometers. It was revealed that through employing the hydrogel isolation technique. Cochleates are able to develop so that they exhibit tiny and particles with greater consistency. It has been discovered that these cochleates a suitable transport system for the encapsulating regarding hydrophobic substances [4]. By employing a binary phase system, it was shown that utilizing a binary phase system like hydrogels that aren't miscible tiny mean particles that are smaller than 500 nm will be produced. Particularly, these nanocochleates were appropriate for encapsulating hydrophobic medicines [8].
Route Of Administration
An effective oral drug delivery method is made possible by nanocochleate. Another method of management thast may be mucosal, topical, sublingual, nasal, or ocular, parenteral, rectal, and subcutaneous, intrathecal, spinal, transdermal, intramuscular, intravenous, intra-articular, and intra-arterial, administration through the lymphatic system, the uterus, the vagina, or any other mucosal sites [3, 8, 15].
DOSAGE FORM
Advantages Of Nanocochlets Drug Delivery System
Limitation Of Nanocochlets Drug Delivery System
Mechanism Of Nanochochlets Drug Delivery
After being administered orally the intestinal tract is where the absorption of nanocochleates occurs. [3]. Lipid was present in significant amounts in the cell membrane. Upon encountering another lipid molecule, Cell membranes allow lipid molecules to bind together and dispersed throughout the cell. Passing through the intestinal epithelium are nanocochleates. And transfer the substances they are carrying into blood vessels [15]. When using a method other than intravenous they traverse the corresponding cell. (In the same way as previously mentioned) as well as enter the circulation. Once it sent to the assigned cell after entering circulation [6].
The Preparation Method
The components of nanocochleates include lipids and multivalent cations together with medicinal substances [10].
The following techniques are typically used to prepare the nanocochleates:
1) The Hydrogel Technique
Using this technique, the initial preparation creates the nanocochleates of drug-loaded microscopic unilamellar liposomes then adding them for polymer A, like using dextran, phosphatidylserine (PS), polyethylene glycol (PEG), etc. Next, two dispersions are combined with another polymer, B. (which could include polyvinyl pyrrolidone, Polyvinyl methyl ether, Ficoll, polyvinyl alcohol, etc.). Both of the polymers cannot mix with the other. Polymers B and A are incompatible with one another, resulting in a two-stage aqueous solution. A cation salt solution was added to the polymers to achieve cationic cross-linking to the system with two phases. So that the second polymer is diffused by the cation and then into the liposome/polymer-containing particles. After formation, the cochleates are cleaned to get rid of the polymer It might potentially be reconstituted in a physiological buffer Using any suitable drug delivery system or lyophilized [4, 10].
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Figure 3: The Hydrogel Technique
2) The capturing technique
This entails making a liposome suspension with a hydrophilic medication or in a liposome's aqueous area or a hydrophobic medication between the bilayers, intercalated, and then added drop wise of a CaCl2 solution to produce a cochleate aggregate. One method for creating liposomes is to mix water using powdered phospholipids or by incorporating a Phase of water into phospholipid coating [7, 14].
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Figure 4: The Capturing Technique
3) A liposome before to the dialysis technique for cochleates
This technique uses a lipid and detergent mixture as the first ingredient and double dialysis is used for the detergent removal process. Calcium chloride solutions are added after the mixture has first been dialyzed using a buffer results in the development of cochleates [4]. Hydrophobic materials could be encapsulated using this technique or medications that have hydrophobic areas, including membrane proteins. The intermediate liposomes created with this technique were tiny and therefore caused tiny cochleates to develop [5]. Combination of cholesterol and phosphatidylserine (9:1 weight ratio) in the buffer used for extraction and the Ionic-free detergent is combined along with a polynucleotide concentration that has been predetermined. After that, the mixture is vortexes for five minutes. A dialysate and buffer mixture in a 1:200 ratio is used to dialyze the solution overnight without the presence of divalent cations. Then three more buffer modifications, which results in the creation of tiny lipid vesicles. By adding Ca2+ ions directly or indirectly, the vesicles are transformed into a cochleate precipitate. Or by using dialysis against two variations of buffers: one with 3 mM Ca2+ ions and the other with 6 mM Ca2+ [4].
4) The method of direct calcium dialysis
In contrast to liposomes prior to the cochleate dialysis technique this process excludes the creation of intermediary liposomes additionally, the cochleates will be in size. Both detergent and lipids are dialyzed directly in opposition to the solution of calcium chloride. Applying this approach, the competition after the detergent has been removed from the Drug, lipid, and detergent micelles and the bi-layer of condensation caused by calcium, which produces a huge, needle-shaped structure. Cholesterol and phosphotidylserine mixture (9:1 weight ratio) mixing non-ionic detergent with extraction buffer with a predetermined polynucleotide concentration, and the mixture is vortexes for For five minutes. The resulting evident, solution without color has dialyzed at ambient temperature opposed to three buffer adjustments. 6 mM Ca2+ is the last dialysis solution that is frequently used. For every alteration, the dialyzed to buffer ratio must be at least one to one hundred. Direct cochleates of calcium are the word used to describe the Calcium-phospholipid precipitates that seem white that develop [7].
5) Aqueous-aqueous binary emulsion system (number five)
Using this technique, tiny Liposomal production when using the film technique or a high pH then combining the produced liposomes with a polymer, like dextran [14]. After that, the Liposomes and dextran process is pumped from one non-miscible polymer to another (PEG). After that, Calcium was introduced and gradually dispersed, forming nanocochleates in various phases the gel was then removed by washing. It has been demonstrated that nanocochleates make it easier to administer injectable medications orally. The cochleates generated with this technique are less than 1000 nanometers in size [13].
Application
Future Prospects
Physiological components include antibodies, proteins, polynucleotides, polypeptides, vitamins, minerals, and amino acids relevant substances supplied as nanocochleate. Cochleates will be used in pharmaceuticals to cover up unpleasant tastes and odors which are oxidation-prone and photo labile. Future research may look into other administration methods such vaginal, transdermal, and intranasal; by actively targeting specific medicine delivery, it serves as a carrier for diseases like cancer, diabetes, TB, and neurological disorders. This is commonly carried out using magneto-cochleates or ligand targets. One popular method of introducing genes into the genome of a malfunctioning cell or organ is to combine proteins and DNA plasmids with cochleates the hematopoietic cells this approach may be able to treat a wide variety of hereditary illnesses [8].
CONCLUSION
A lipid-based medication delivery technology called nanocochleates has promise for oral administration of Lots of drug. A new technological platform for oral and systemic medication administration is represented by cochleate delivery vehicles. It has been demonstrated that nanocochleate Delivery methods might be widely used for a range of physiologically significant compounds. Encochleation can enhance the formulation's properties and produce a better final product, improving bioavailability, decreasing toxicity, boosting efficacy, and stabilizing processes and shelf life. Given that cochleates are created when negatively charged liposomes contact ionotically, as well as bivalent cations, it makes sense to microencapsulate cationic medications and use them as cochleation bridging agents. As a result, these hydrophilic and multi-cationic medications and derivatives, is capable of being effectively enclosed within cochleates and used acting as a connecting element between cochleates and nanocochleate particle . Cochleates' ability to bridge agent in the form of nanocochleate particles. Because of these special qualities, cochleates and nanocochleates can provide hydrophilic, charged medications that pass through cellular membranes. Future patient outcomes could be enhanced by more research and development that could fundamentally alter the drug delivery environment. Briefly said, oral drug delivery techniques could be completely transformed by nanocochleates. resulting in the creation of extra popular and effective therapies for a variety of illnesses.
REFERENCES
Samruddhi More*, Prajakta Kangutkar, Shital Kamble, Dr. D. R. Jadage, Nanocochleates As A Novel Lipid-Based Nano Carrier For Enhanced Drug Delivery, Int. J. of Pharm. Sci., 2025, Vol 3, Issue 5, 1535-1544 https://doi.org/10.5281/zenodo.15380480
10.5281/zenodo.15380480
