1School of Pharmacy, Abhilashi University, Chail-Chowk Mandi, Himachal Pradesh, 175028.
2Abhilashi college of Pharmacy, Ner-chowk Mandi, Himachal Pradesh, 175008
Solid cross-linked porous nanoscale polymeric structures are known as nanosponges. This broad idea includes hydrogels and metal organic frameworks. This manuscript focuses on nanosponges, their types and details related to its crucial type cyclodextrin based nanosponges, their methods of preparation and applications. Cyclodextrins are starch-derived cyclic oligomers of glucose. Cyclodextrins have the rare capacity to form inclusion host-guest complexes with numerous hydrophobic substances due to the unique structure created by the combination of the outward hydrophilicity and the inside hydrophobic surface. These complexes might improve the solubility of the guest molecules and stabilize the molecule without causing any other alterations in their favorable properties. These characteristics along with the flexibility to use various crosslinkers and the high polymeric surface, make these sponges particularly well-suited for a wide variety of applications.
Innovative medication delivery systems called nanosponges are minuscule sponge-like structures with cavities. These cavities can be filled with drugs and have pores between 1 and 2 nanometers in size.(1) Nanosponges have a sponge-like morphology and are very small in size. These are tiny, mesh- like structures that may enclose a wide range of different substances. They have a demonstrated spherical colloidal nature and are said to have a high capacity for solubilization.(2) Drugs that are poorly soluble in water can be solubilized using nanosponges, which also give extended release and increase drug bioavailability. Due to their internal hydrophobic chambers and exterior hydrophilic branching, nanosponges have unmatched flexibility and can load both hydrophilic and hydrophobic medicinal molecules.(3)
Components of Nanosponges
Table1: The major components used in formulation of nanosponges
Types of Nanosponges
Table2: Categorization of nanosponges into various generations based on their evolution.(6)
Cyclodextrin based ether nanosponges
By reacting CDs with cross-likers containing epoxide groups such as epichlorohydrin, bisphenol A diglycidyl ether, ethylene glycol diglycidyl ether, etc., CD-based ether NSs are frequently created. This particular class of NSs demonstrates strong chemical resistance and variable swelling capabilities.(7)
Cyclodextrin based urethane nanosponges
Diisocyanates are primarily used in the synthesis of urethane (or carbamate) CD-NSs. Their robust structure, great resistance to chemical deterioration and little swelling extent in both aqueous and organic conditions serve as distinguishing features. Li and Ma created the first carbamate CD-NSs which are utilized to remediate wastewater by reacting CD with hexamethylene diisocyanate and toluene-2,4-diisocyanate.(8) These NSs outperformed activated carbons in the elimination of several organic compounds such as p-nitrophenol which was reduced to ppb levels even at low concentrations.(9)
Cyclodextrin based carbonate nanosponges
Active carbonyl chemicals including as 1,1'-carbonyldiimidazole, Tri-phosgene, and diphenyl carbonate are used in the synthesis of CD-based carbonate NSs. Short cross-linking bridges decreased swelling ability, strong stability to acidic and mildly alkaline solutions are all characteristics of these NSs.(10) Carbonate NSs exhibit a limited surface area (about 2 m2/g) and a strong attraction for some organic compounds just like urethane NSs do.(11)
Cyclodextrin based ester nanosponges
Ester NS is typically created by combining CDs with dianhydrides or di/ poly carboxylic acids such citric acid, ethylenediamine-tetra acetic dianhydride (EDTA dianhydride), butane tetracarboxylic dianhydride and pyro melic dianhydride.(12)
The extension of the previously mentioned CD polymers range of application and the emergence of a new generation of NSs were made possible by the incorporation of desired functionalities. There are three ways to introduce certain moieties: Functionalization of an NS after cross-linking but before cross-linking CD functionalization or simultaneous addition of a functionalizing agent and a cross-linking agent step.(13)
Stimuli-sensitive polymers adapt to changes in their environment by changing their structure, permeability or color. The morphology, supramolecular processes and molecular processes that are stimuli sensitive are what enable an organism to perceive a stimulus and respond to it. (14) Stimuli-sensitive nano-carriers are renowned for their potential to boost therapeutic efficiency with a minimum of adverse effects, as well as their controlled target release upon initiation by stimulating signals or particular transport routes.(15)
When a template molecule is present during the synthesis of a polymer, a technique called molecular imprinting can be used to provide three-dimensional polymers molecular recognition properties.(16)
Cyclodextrin-Based Nanosponges
A family of molecular cages known as cyclic 1,4-linked oligosaccharides with hydrophilic exterior surfaces and a lipophilic inside is known as cyclodextrins (CDs). When creating nanosponges, cyclodextrins (CDs) have been the most often used materials.(17,18) Early in the 1950s, physicochemical characteristics of CD were found and ever since, the pharmacological and physicochemical qualities such as stability, solubility and bioavailability of active moieties have then been improved.(19) It has been noted that cyclodextrin complexes made with biocompatible hydrophilic polymers can improve the solubility of encapsulated classes in aqueous conditions.(20) A novel hyper-crosslinked nanostructured material can be created by reacting cyclodextrins with crosslinkers called "nanosponges".(21)
Components of Cyclodextrin Based Nanosponges
Table3: Components of cyclodextrin based nanosponges
Characteristics
Types of Cyclodextrin Based Nanosponges
Table4: Classification of cyclodextrin based nanosponges Based On Polymer Used(30)
Based On Functional Groups(6,31)
Methods of Preparation
In the solvent evaporation approach, the fusing step is skipped and the cross-linking agent is instead solubilized using solvents like DMSO or DMF.(33) The polymer is combined with a polar aprotic solvent and the resulting combination is added to a cross-linker solution and refluxed for one to forty-eight hours. The end result is produced by mixing a substantial amount of distilled water with cold solution. Finally, filtration is used to recover the finished product and Soxhlet extraction is used to purify it over an extended period of time.(34) By either a non-inclusional or an inclusional process, spherical, solid nanostructures with high water solubility are produced. High pressure homogenization involves homogenizing prepared nanosponges in water at continuous speed for 10 minutes minimizes the size of NS.(25)
In the initial step of ultrasound-assisted manufacturing, cyclodextrins and cross-linking agents are combined without the need of solvents.(35) Anhydrous -CD and DPC are taken in a vial, placed in an ultrasonic bath with water that has been pre-heated to 90°C and then sonicated for five hours. Additionally, the solvent evaporation and melt technique's crystallization and purification procedures are the identical.(36)
Microwave irradiation is the easiest way for synthesizing CDNS and it considerably slows down reaction time. The NS that is produced has more crystallization.(37) Microwave aided manufacturing showed a four-fold reduction in reaction time compared to typical melt technique. The procedure produced crystallinity and a homogenous distribution of the particle size.(38)
In this method, the cross-linking agent is melted with a CD and all of the ingredients are homogenized before being heated at 100°C for five hours while being stirred magnetically. The above matrix is then given time to cool. To get rid of by-products and unreacted components.(6,39)
Drug Loading in Blank Nanosponges
The drug loading capabilities of NS are different for para-crystalline and crystalline forms. When compared to para-crystalline NS, crystalline NS results in a larger drug pay load. Due to the hydrophobic CD channels that are surrounded by hydrophilic nanocavities in the polymeric matrix, these nanosponges have a variety of mesh polarities, enabling strong interactions with drugs of different lipophilicities and structural types.(40,41) The drug or herbal extract is dissolved in ethanol or suitable solvent with uniform agitation for 15 minutes and then keeping the mixture undisturbed for 24 hours. Then the resultant is centrifugated and supernatant of the mixture is lyophilized.(42)
The loading capacity of the nanosponges is calculated using formula(43):
Characteristic Evaluation of Nanosponges
Calculating the initial or beginning weights of raw materials and the end weight of nanosponges will produce the production yield (PY).
Yield of production = [Actual mass of nanosponges/Theoretical mass (drug + polymer)] × 100
Different batches percentage yields were calculated using weighing the dried nanosponges.(44,45)
The FTIR spectra of optimized loaded NS and Blank NS were captured and analyzed for potential chemical interactions. The translucent pellets of these samples were generated by mixing these compounds with potassium bromide. FTIR spectra was acquired in the area of 4000–400 cm?1(46)
The stability and durability of the Nanosponges was estimated using a zeta potential study. Zeta potential is a metric for electrostatic charge impact. This fundamental force is what separates nearby particles from one another. Depending on the strength of both forces, the overall effects can be either attraction or repulsion.(47)
In a volumetric flask, correctly weighed nanosponges (10 mg) were added to 5 ml of methanolic HCl (HCl: Methanol-10:1) to determine the entrapment efficiency. The flask was shaken with a vortex mixer for one minute.(48) The Methanolic HCl was used to create a volume up to 10 ml. After that, the mixture was diluted, filtered and the Spectrometric analysis was used to determine the drug concentration at 295nm.(49)
5. In-vitro drug release-Dissolution Study:
The prepared formulation was subjected to a 12-hour in vitro drug release study utilizing an Electrolab model dissolution tester USP Type-2 apparatus (rotating paddle) set at 100 rpm and a formulation with a temperature of 37±0.5°C was added to the 900ml medium.(50) To maintain a constant volume, 10 ml samples were taken out of the dissolving medium at predetermined intervals and replaced with new medium. Using a UV- visible spectrophotometer, the sample solution's absorbance was measured at 231 nm to determine whether the model drug was present.(51,52)
6. X-Ray Diffraction Technique
7. Porosity or swelling index(53)
8. Differential Scanning Calorimetry
9. Microscopic Technique
10. Photodegradation studies (54)
ROLE IN DRUG DELIVERY
When drugs are delivered by nanosponges, they are only released at the targeted spot hence preventing their circulation throughout the body.(55)
Table5: Various applications of cyclodextrin based nanosponges in targeted and controlled release drug delivery
Drug compounds that are prone to deterioration when exposed to water, oxygen (air), heat or radiation can be stopped from degrading by using cyclodextrin nanosponges.(60) Nanosponges are being used in numerous studies on these interactions. The nanosponges prevent oxidation, hydrolysis, racemization, polymerization and enzyme hydrolysis from happening to the drug molecules.(61)
Table6: Various applications of cyclodextrin based nanosponges in improving stability.
3. Enhanced solubility
Poor solubility of BCS (Biopharmaceutical Classification System) class II medications possesses a challenge in their preparation.(65) However, these medications can be more effectively integrated into cyclodextrin nanosponges. By increasing their wetting and solubility in water, these nanocarriers increase their aqueous solubility through the formation of inclusion complexes.
Table7: Various applications of cyclodextrin based nanosponges in enhancing solubility:
An established route of administration with good patient compliance is oral medication delivery. Due to poor solubility, ineffective intestinal permeability, and pre-systemic activation, delivering molecules via oral route presents difficulties. Nanosponges made from cyclodextrin have shown promise as oral delivery without sacrificing any safety concerns.(69)
For topical drug delivery, nanosponges may be included in creams and gels. Although they haven't been extensively studied, nanosponges could be a very effective method for treating skin conditions. If successfully entrapped, nanosponges enhanced drug delivery via topical gel in addition to drug targeting.(70,71)
The pulmonary route is a substitute for parenteral drug delivery but the drug has to be in the form of aerosol to be delivered by this route. The advantage of the nanosponges is their lower interparticle forces of attraction and improved flow properties. Additionally, they have a small, thin and low bulk density. Their increased deposition in the lower pulmonary area is the result of their dynamic diameter.(72)
CONCLUSION
Nanosponges are innovative crosslinked carriers which are used to deliver variety of drugs to targeted sites and plays vital role in increasing their bioavailability. Drugs that are either lipophilic or hydrophilic can be incorporated into the nanosponges which release them in a regulated and predictable way at the target location. It can be modulated by adjusting the polymer to water ratio, the release rate, particle size, and cross-linker. Nanosponges permit the insoluble medications and safeguard the active components from controlled physicochemical deterioration. Due to their diminutive size and spherical shaping, they can be created in a variety of ways or dose types/ forms like aerosol, topical, parenteral, capsules and pills. Cyclodextrin nanosponges are a rapidly growing area of nanotechnology with numerous uses in medicine delivery, research and targeting among other elements due to their distinct size-dependent characteristics and porous nature. They offer the potential to create novel therapeutic approaches. Their capacity to seize drugs and exercise control releasing features provide a novel method of medication delivery that raises the level of the drug targeting. Consequently, cyclodextrin nanosponges hold out a lot of hope for achieving the site-specific and regulated delivery objectives which can also provide fresh viewpoints in the near future in the treatment of difficult disorders.
ABBREVIATIONS
REFERENCES
Chinu Kumari , Dev Prakash Dahiya , Kanika , Nikhil Rana , Rahul Sharma , Abhilash Rai , Abhishek Soni, Cyclodextrin Based Nanosponges: A Novel Approach For Targeted Drug Delivery, Int. J. of Pharm. Sci., 2024, Vol 2, Issue 3, 46-5. https://doi.org/10.5281/zenodo.10775995
10.5281/zenodo.10775995
