Formulation Optimization and Biopharmaceutical Evaluation of Imatinib Mesylate Loaded β-cyclodextrin Nanosponges

Abstract

Background: Many researchers have prepared and evaluated nanosponges and claimed their advantages as an effective drug carrier, especially it was observed prominently in case of anti-fungal drugs. The materials employed to synthesize nanosponges were mainly crosslinking agents, different beta-cyclodextrin and other cellulose-based polymers. Many of them had used ratio proportions of cross-linking agents, d polymers to synthesize these nanosponges which ultimately produce a porous mesh-like network known as nanosponges where actually drug is encapsulated or loaded. Objective: In the present investigation, we observed the effect of various levels of crosslinking agents and beta-cyclodextrin concentrations on porosity, drug encapsulation, zeta potential and drug release by employing the quality by design approach to synthesize nanosponges rather than merely keeping both concentrations in proportions. Methods: We have slightly modified the method reported earlier i.e. melting method in which we have used rota evaporator receiver vessel for melting cross-linking agent and beta- cyclodextrin, rotated at 20 RPM at 100°C. Results: In a quality by design approach, we observed that out of four dependent variables i.e. porosity, drug loading, zeta potential and drug release, three significantly depend on the crosslinking of beta-cyclodextrin molecules which is highly appreciated by the amount of cross-linking agent present in the reaction. The pharmacokinetics of Imatinib loaded optimized nanosponges were compared with the reference product to observe the pattern of absorption and disposition. Conclusion: Nanosponges synthesized by optimization technique could be effective means of anti-cancer drug oral administration as they encapsulate the drug effectively and offer a prolonged release of drug which gradually releases the drug and avoids unnecessary exposure of the drug.

Evaluation and Characterization of Curcumin-β-Cyclodextrin and Cyclodextrin-Based Nanosponge Inclusion Complexation

“…Nanosponge is an attractive drug carrier to be considered for pharmaceutical applications [ 41 , 42 ], due to its stability, insolubility, biocompatibility, and ability to encapsulate drugs through the formation of inclusion and non-inclusion complexes. In addition, nanosponge has been reported to enhance the solubility of different drugs [ 43 , 44 , 45 ], enhance the permeation and retention of dermal formulations [ 43 , 46 ], control the rate of drug release [ 47 , 48 ], increase drug stability and lessen drug degradation [ 47 , 49 ], and help mask the drug’s unpleasant taste [ 50 ].…”

The ascension of nanosponges as a drug delivery carrier: preparation, characterization, and applications

“…There is a direct relation between the degree of crosslinking and number of substitution where greater the number of substituents can provide higher degree of crosslinking thus yielding highly porous NSs having a mesh type networking in the internal structure [ 70 ]. A change in production process may lead to varying physicochemical properties in the material that formed, because of the functional group occupying different sites on the parent compound.…”

History of Cyclodextrin Nanosponges

“…It consists of exploring the behavior of NSs in various experimental conditions in a limited number of tests and straightforward identification of the variables that affect the system the most, taking into account the synthesis [141] or the formulation process [14][15][16]. For example, this approach was adopted by Kamble and co-workers to synthesize NSs considering the effect that various levels of crosslinking agents and βCD concentrations had on porosity, drug encapsulation, zeta potential and drug release [17]. Furthermore, Pushpalatha and co-workers optimized the curcumin-resveratrol loaded NS hydrogel formulation using a factor 3-level Box-Behnken design.…”

“…The synthesis of NSs over the years has evolved towards greener processes, starting from the use of organic solvents, which made the washing step of NSs necessary because of the toxicity, passing through water to the most recent solvent-free synthesis [13]. NS formulations have also been optimized by means of mathematical tools to ensure the best solution for the delivery of drugs [14][15][16][17]. The number of analytical tools has increased in order to improve the characterization of NSs and better understand their properties and behavior.…”