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Central Composite Design for Optimization of Mitomycin C-Loaded Quantum Dots/Chitosan Nanoparticles as Drug
Fariza Aina Abd Manan1, Nor Azah Yusof1,2, Jaafar Abdullah1,2
1Institute of Nanoscience and Nanotechnology, Universiti Putra Malaysia, UPM Serdang, Serdang 43400, Selangor, Malaysia.
Abstract:
Cancer is one of the most devastating diseases that leads to a high degree of mortality worldwide. Hence, extensive efforts have been devoted to the development of drug nanocarrier vectors as a potential new cancer treatment option. The main goal of this treatment is to deliver an anticancer medicine successfully and effectively to the patient's cells using non-toxic nanocarriers. Here, we present a drug delivery system to emphasize the optimization of an anticancer drug-loaded formulation using Mitomycin C (MMC) encapsulated in chitosan nanocarrier conjugated with a bioimaging fluorescence probe of Mn:ZnS quantum dots (MMC@CS-Mn:ZnS). Additionally, the Response Surface Methodology (RSM), which uses a quadratic model to forecast the behaviour of the nano-drug delivery system, was used to assess the optimization of encapsulation efficiency. In this investigation, the core points of the Central Composite Design (CCD) model were used with 20 runs and 6 replications. The encapsulation efficiency (EE%) was measured using UV-Vis spectroscopy at 362 nm. The highest EE% is 55.31 ± 3.09 under the optimum parameters of incubation time (105 min), concentration of MMC (0.875 mg/mL), and concentration of nanocarriers (5.0 mg/mL). Physicochemical characterizations for the nanocarriers were accessed using a nanosizer and field-emission scanning electron microscopy (FESEM). Three independent variables for the evaluation of the encapsulation efficiency were used, in which the incubation time, concentration of MMC, concentration of nanocarriers, and correlation for each variable were studied. Furthermore, the MMC drug release efficiency was carried out in four different solution pHs of 5.5, 6.0, 6.5, 7.0, and pH 7.5, and the highest cumulative drug release of 81.44% was obtained in a pH 5.5 release medium, followed by cumulative releases of 68.55%, 50.91%, 41.57%, and 32.45% in release mediums with pH 6.0, pH 6.5, pH 7.0, and pH 7.5. Subsequently, five distinct mathematical models-pseudo-first-order, pseudo-second-order, Hixson-Crowell, Korsmeyer-Peppas, and Higuchi kinetic models-were used to fit all of the drug release data. The Korsmeyers-Peppas model was found to fit it well, highlighting its importance for the log of cumulative drug release proportional to the log of time at the equilibrium state. The correlation coefficient value (R2) was obtained as 0.9527, 0.9735, 0.9670, 0.9754, and 0.9639 for the drug release in pH 5.5, pH 6.0, pH 6.5, pH 7.0, and pH 7.5, respectively. Overall, from the analysis, the as-synthesized MMC nanocarrier (MMC@CS-Mn:ZnS) synergistically elucidates the underlying efficient delivery of MMC and leverages the drug loading efficiency, and all these factors have the potential for the simultaneous curbing of non-muscle invasive bladder cancer reoccurrence and progression when applied to the real-time disease treatment.
Insights
This study optimized a novel nanocarrier system for delivering Mitomycin C (MMC) chemotherapy. The developed MMC-loaded chitosan nanocarrier conjugated with quantum dots shows potential for effective cancer treatment.
Area of Science:
- Nanotechnology and Drug Delivery
- Materials Science
- Oncology
Background:
- Cancer remains a leading cause of mortality worldwide, necessitating advanced therapeutic strategies.
- Drug nanocarrier systems offer a promising approach for targeted and effective delivery of anticancer agents.
- Chitosan nanocarriers conjugated with quantum dots provide a platform for enhanced drug loading and bioimaging.
Purpose of the Study:
- To optimize an anticancer drug formulation using Mitomycin C (MMC) encapsulated in chitosan nanocarriers conjugated with Mn:ZnS quantum dots (MMC@CS-Mn:ZnS).
- To evaluate the encapsulation efficiency and drug release kinetics of the optimized nanocarrier system.
- To assess the potential of the developed nanocarrier for treating non-muscle invasive bladder cancer.
Main Methods:
- Response Surface Methodology (RSM) with a Central Composite Design (CCD) was employed to optimize encapsulation efficiency.
- Encapsulation efficiency was determined using UV-Vis spectroscopy.
- Physicochemical characterization was performed using nanosizer and field-emission scanning electron microscopy (FESEM). Drug release studies were conducted at various pH levels, and kinetic models (Korsmeyer-Peppas) were applied.
Main Results:
- The highest encapsulation efficiency (EE%) of 55.31 ± 3.09% was achieved under optimized conditions (incubation time: 105 min, MMC concentration: 0.875 mg/mL, nanocarrier concentration: 5.0 mg/mL).
- The nanocarrier system exhibited pH-dependent drug release, with the highest cumulative release (81.44%) observed at pH 5.5.
- The Korsmeyer-Peppas model best described the drug release kinetics, indicating a diffusion-controlled release mechanism.
Conclusions:
- The synthesized MMC@CS-Mn:ZnS nanocarrier system demonstrates efficient drug loading and controlled release capabilities.
- The pH-responsive drug release profile suggests potential for targeted delivery in acidic tumor microenvironments.
- This optimized nanocarrier holds promise for the simultaneous treatment of recurrence and progression in non-muscle invasive bladder cancer.
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