Department of Pharmaceutics, School of Pharmacy, SRTMU, Nanded. (431606).
*Corresponding Author E-mail: vaishnavigole05@gmail.com
ABSTRACT:
The solid porous particles have a nanocavity structure in which drugs are encapsulated known as nanosponges. There are five types of nanosponges. Nanosponges size varies from 1um and less than 1 um. Nanosponges are stable at high temperatures. It has high drug loading capacity. Nanosponges formulation overcomes stability, delayed-release activity, and solubility-related problems. Nanosponges can deliver the drug through oral, parenteral, and topical routes. The current review focuses on nanosponges in drug delivery systems including their synthesis, characterization, and diverse applications.
KEYWORDS: Nanosponges, Nanocavity, Polymers, Crosslinkers, solvent evaporation.
INTRODUCTION:
Nanosponges are tiny, solid, porous particles having nanocavity filled with both hydrophilic and hydrophobic drug substances.2 The average size of nanosponges is below 1 um. Carbon-coated metallic Nanosponges, beta-cyclodextrin- based Nanosponges, Hypercross-linked polystyrene Nanosponges, Silicon Nanosponges particles, and Titanium-Based Nanosponges are the five varieties of nanosponges. Nanosponges bind to the specific surface of the target site and release drug in a controllable and sustainable manner.6 They enhance the bioavailability of poorly water-soluble drugs.7 Nanosponges are further formulated into solid (tablet, capsules), semisolids (hydrogel), liquid (sterile water, saline, or other aqueous solutions).13,14 Topical nanosponges are more apparent due to their passive accumulation and high permeability at the target site.
Advantages:9,10
· Nanosponges are stable between the range of PH 1 to 11 and at higher temperatures.
· Nanosponges are non-toxic, irritant-free, and allergy-free.
· Nanosponges are easy to prepare, free-flowing, and cost-effective.
· Nanosponges improve the water solubility of hydrophobic drugs.
· Because of their small pore size (0.25um), bacteria cannot penetrate nanosponges, they operate as self-sterilizers.
· Nanosponges minimize the side effects of drugs.
· Nanosponges have an ability to the entrap only small molecules.
· The degree of crystallization decides the loading capacity of nanosponges.
· Polymers–The type of polymer utilised for preparation affects the formulation and performance of Nanosponges. Nanosponges should have a cavity large enough to entrap drug molecules of a specific size for complexation. Hyper cross- linked Polystyrenes, Methyl-Cyclodextrin, Alkyloxycarbonyl Cyclodextrins, 2-HydroxyPropyl-Cyclodextrins, and others are examples.
· Copolymers- “It is a complex of two or more types of monomers units formed through condensation polymers”. Examples- Ethyl cellulose, polyvinyl alcohol,
· Crosslinkers-The selection of cross-linker depends upon the structure of polymer and drug to be formulated. Examples:- Diarylcarbonates, Carbonyldiimidazoles, Diphenyl Carbonate.
· Active Pharmaceutical Ingredient (API)- The molecular mass of molecules that are used for formulation ranges between 100 - 400 Daltons. The solubility of the drug in water is not more than 10mg/ml. The melting point of Active Pharmaceutical Ingredient (API) is less than 2500C.
1. Emulsion solvent evaporation method –Nanosponges can be prepared by using different proportions of polyvinyl alcohol and ethyl cellulose. To improve drug loading capacity the various ratios of drug to polymer are used. The dispersed phase is prepared by dissolving ethyl cellulose and drug substances in 20ml of dichloromethane. The continuous phase is prepared by dissolving polyvinyl alcohol in 150ml of distilled water. The continuous phase is dropwise added into disperse phase, then mixture stir for 1000rpm for about 2 hours by using magnetic stirrer. Nanosponges are collected filtered and dried in oven for 400C for one day.25
2. Polar aprotic solvent method - nanosponges is prepared by mixing of polymer with a polar aprotic solvent such as dimethyl sulfoxide, dimethylformamide. In this mixture the crosslinkers/ polymer in the ratio of 40:160 added. The above mixing carried out at 100C temperature to the reflex temperature of solvent, for 1 hour to two days. After mixing is complete, the resultant solution is allowed to cool to room temperature. The resultant product was then added to an excess of bidistilled water, vacuum filtered, and refined by soxhlet extraction with ethanol. The resulting product was vacuum dried and ground into a homogenous powder in a mechanical mill.21
3. Ultrasound assisted synthesis- A polymer and crosslinker react in absence of solvent under sonication for 5 hours. The resulting nanosponges is spherical and uniform in size. The flask containing mixture of the polymer and cross linker in specific molar ratio is placed in an ultrasound bath containing water heated at 900C. The wash product purified by using soxhlet extraction with ethanol, dried and stored at 250C.16
4. Loading of drug into nanosponges- The nanosponges pretreated to obtain a below 500 nm mean particle size. Nanosponges are suspended in water to form suspension by using sonicator to avoid aggregations of nanosponges to obtain colloidal fraction the nanosponges suspension is subjected to centrifugation. The supernatant is separated and product sample is dried by Freeze drying.16
1. Microscopic study-The microscopically characteristics of the nanosponges, drug and product (drug nanosponges complex) is studied by using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). The differences in the crystallization state and product seen under an electron microscope indicates inclusion complex formation.11
2. Zeta potential - It is used to measure surface charge by using particle size equipment with the additional electrode. The nanosponges sample diluted with 0.1mol/L potassium chloride and placed in a electrophoretic cell of the 15v/cm electric field. After averaging of the total measurement the mean hydrodynamic diameter and polydispersity index is determined.12
3. Loading efficiency – Loading efficiency is a ratio of actual drug content in nanosponge to theoretical drug content. It is determined by using HPLC and UV spectrophotometer.1
4. Solubility studies- An inclusion complexes as the phase solubility method is the most widely approached technique for analysis of nanosponges. The plot of phase solubility show degree of completion. The solubility studies can determine the pH of the drug, solubulization and also the factors affecting drug solubility.3
5. Particle size and polydispersity index-The particle size of nanosponges can be determined by 90 + particle size re- equipped with MAS OPTION particle sizing software of the dynamic light scattering.17
6. Infrared spectroscopy- The IR spectroscopy determined the reaction between nanosponges and the drug in solid state. When a compound is formed, The nanosponges band alter.4
7. Thin layer chromatography (TLC)- In TLC, the retention factor of a drug molecules helps in identifying the complex formation between the drug molecules and nanosponges.23
8. Thermoanalytical method- The method determine the melting, oxidation, decomposition, evaporation changes of drug substance. These changes indicates the complex formation.12
9. X- Ray diffractometry and the single crystal x-ray structure analysis- The inclusion complexation in solid state detected by using x-ray diffractometry. The diffraction patterns change with the formation of inclusion complex and also crystalline nature of drug changes.8
· To enhance solubility –A drug having low solubility and high permeability i.e. poor bioavailability. The bioavailability of medications with low solubility and high permeability, such as BCS II pharmaceuticals, is improved using nanosponges. By lowering the crystallinity of the medication, nanosponges improve its wetting capacityeability.
Example:- Itraconazole nanosponges.
· Nanosponges as a sustained delivery system- Nanosponges improve absorption of those drugs having slow and highly variable GIT absorption. Example- Acyclovir poorly absorbed in GIT but nanosponges showed sustained a release of the drug.18,19
· Nanosponges in drug delivery- Nanosponges can be formulated in number of doses form as parenteral, topical, aerosol, tablet and capsules.22
· Topical agents- The nanosponges containing topical agent release drug in controllable and sustainable manner. Local anesthetics, antibiotics and antifungal drugs easily formulated as topical nanosponges such as lotion, cream, ointment, powder or liquids.15
· Gases provided by nanosponges carrier — For the treatment of hypoxia, oxygen is administered topically via nanosponges formulation. Hypoxia is a lack of enough oxygen that has been linked to a variety of diseases ranging from inflammation to cancer.12
· Nanosponges as a carrier for biocatalyst - nanosponges is a suitable carrier for the delivery of protein enzyme antibodies and macromolecules.20
Nanosponges are tiny solid porous particles having nanocavity filled with both hydrophilic and hydrophobic drug substances. They are colloidal nanocarriers. Nanosponges technology gives better patients compliances, increases flexibility of formulation and also enhances stability of drug substances. They minimize side effects by targeting the drug to the specific site.Nanosponges, further formulated into solid ( tablet, capsules), semisolids (hydrogel), liquid (sterile water, saline or other aqueous solutions). Topical nanosponges are more apparent due to their passive accumulation and high permeability at the target site.
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Received on 11.02.2022 Modified on 07.05.2022
Accepted on 02.07.2022 ©Asian Pharma Press All Right Reserved
Asian J. Res. Pharm. Sci. 2022; 12(3):210-212.
DOI: 10.52711/2231-5659.2022.00037