Extraction Of Camptothecin Research Articles

Extraction of camptothecin and 10-hydroxycamptothecin from Camptotheca acuminata fruits by natural deep eutectic solvent

A natural deep eutectic solvent-based ultrasound-assisted simultaneous extraction (NADES-UAE) of camptothecin (CPT) and 10-hydroxycamptothecin (10-HCPT) was established. The 1.31 mg of CPT and 1.66 mg of 10-HCPT were obtained from each gram of the fruit powder of Camptotheca acuminata under the optimum conditions with a water content of 20%, a liquid-solid ratio of 12 mL/g and an ultrasound time of 20 min. The recovery efficiencies of CPT and 10-HCPT after AB-8 resin enrichment were 70.5% and 74.8%, respectively. The stronger interaction between NADES3 which was screened from 12 kinds of NADES and target components compared with methanol or water was demonstrated using molecular dynamics simulation. Moreover, the recovered NADES3 could be reused at least 4 times. The present research provided an efficient, environment-friendly, and sustainable method for extracting and recovering CPT and 10-HCPT from the fruits of C. acuminata.

Optimisation of enzyme-assisted extraction of camptothecin from Nothapodytes nimmoniana and its characterisation.

Efficient extraction of camptothecin (CPT), an anticancer agent from the commercial source Nothapodytes nimmoniana (J. Graham) Mabb in India, is of paramount importance. CPT is present in the highest concentration in the stem portion, and the stem can be readily harvested without uprooting the plant. The fluorescence microscopy mapping of the bark matrix for CPT revealed its presence in a free form within both the outer (epidermal and cortical tissues) and inner (xylem and phloem tissues) sections. The bark matrix primarily consists of cellulose, hemicellulose, and lignin, rendering it woody, rigid, and resistant to efficient solvent penetration for CPT extraction. We proposed a hypothesis that subjecting it to disruption through treatment with hydrolytic enzymes like cellulase and xylanase could enhance solvent diffusion, thereby enabling a swift and effective extraction of CPT. The present study was aimed at enzyme-assisted extraction, using cellulase and xylanase for hydrolytic disruption of the cells to readily access CPT from the stem of the plant N. nimmoniana (J. Graham) Mabb. The hydrolytic cell disruption of ground powder from the stem bark was studied using cellulase and xylanase enzymes. The enzymatically pretreated stem bark powder was subsequently recovered by filtration, dried, and subjected to extraction with methanol to isolate CPT. This process was optimised through a Box-Behnken design, employing a one-factor-at-a-time approach to assess parameters such as enzyme concentration (2-10% w/w), pH (3-7), incubation time (6-24 h), and solid-to-solvent ratio (1:30-1:70 g/mL). CPT was characterised using proton nuclear magnetic resonance (1H-NMR) and Fourier transform infrared (FTIR) spectra, and a high-performance liquid chromatography (HPLC) method was developed for quantification. The cellulase and xylanase treatment resulted in the highest yields of 0.285% w/w and 0.343% w/w, with efficiencies of 67% and 81%, respectively, achieved in a significantly shorter time compared to the untreated material, which yielded 0.18% with an efficiency of only 42%. Extraction by utilising the predicted optimised process parameters, a nearly two-fold increase in the yield, was observed for xylanase, with incubation and solvent extraction times set at 16 and 2 h, respectively. Scanning electron microscopy (SEM) images of the spent material indicated perforations attributed to enzymatic action, suggesting that this could be a primary factor contributing to the enhanced extraction. Enzyme-mediated hydrolytic cell disruption could be a potential approach for efficient and rapid isolation of CPT from the bark of N. nimmoniana.

The role of hydrogen bonding in solubilizing camptothecin in hydrophilic and hydrophobic ionic liquids

Utilizing ionic liquid (IL)-water mixtures as selective extraction solvents for raw materials from natural sources represents an efficacious approach; however, elucidating the underlying mechanisms inherent in various types of IL-aqueous solutions continues to pose a significant challenge. In this study, molecular dynamics simulations and density functional theory calculations are employed to illuminate the influence of the functional anion within ILs and the water content on the solvation mechanism and phase separation phenomena observed during the extraction of camptothecin (CPT) using aqueous IL solutions. The simulation results show that the anions in ILs preferentially dissolve CPT through hydrogen bonding at low water concentrations. As the water concentration increases, the hydrophobic IL binds more tightly to CPT, enabling the water to self-aggregate. The anions in hydrophilic IL form hydrogen bonds with water instead, further enhancing the dissolution of CPT. This work reveals the mechanism of phase separation and solvation of different types of IL aqueous solutions, which is helpful in developing new drug extraction and purification technologies.

Variation in seedling vigour and camptothecin content of Pyrenacantha volubilis Wight: insights for domestication

As a pioneering work in the field of domestication of Pyrenacantha volubilis Wight, an anti-cancer drug (camptothecin) yielding plant, this study identifies superior seed sources of southern peninsular India for various parameters related to its growth and yield. The experiment was set up following the common garden experiment protocol in Completely Randomised Design. Laboratory extraction of camptothecin from whole seeds was carried out using High Performance Liquid Chromatography. Whereas seeds from Kizhoor population were the heaviest (test weight of 171.5 g), seedlings obtained by sowing the seeds from Villiampakkam population performed better in terms of total yield per plant (5.25 g dry weight) as well as total camptothecin yield per hectare (223.125 g). Almost three times variation was observed in the experiment between the poorest and the best performing populations. We attempt to discuss the potential for domestication, large-scale planting and sustainable harvesting of this promising and versatile new cash crop.

An efficient approach for the enzyme-enhanced extraction of camptothecin and 10-hydroxycamptothecin from the samara of Camptotheca acuminata using an ionic liquid solution

Abstract An efficient approach for enzyme-enhanced extraction using an ionic liquid solution (ILEEE) of the major alkaloidal components camptothecin (CPT) and 10-hydroxycamptothecin (HCPT) from the samara of Camptotheca acuminata is presented. The enzyme pretreatment in an aqueous ionic liquid (IL) media was used for the enhancement of extraction yield. The activity of hemicellulase was investigated in various ILs with imidazolium-based cations ([C2MIM]+, [C4MIM]+, [C6MIM]+, [C8MIM]+, [C10MIM]+) and anions (Br−, Cl−, Ac−, HSO4−, NO3−). The optimal ionic liquid for the hemicellulase extraction process was found to be a 0.75 M [C8MIM]Br aqueous solution. Single factor experiments and Box–Behnken design found the optimal operational parameters for ILEEE to be an incubation temperature of 40 °C, incubation time of 12 h, extraction phase of pH 4, liquid-solid ratio of 30 mL/g, 0.75 M [C8MIM]Br and a hemicellulase concentration of 0.441 mg/mL. Under these optimized extraction conditions, the total yield of CPT and HCPT was 1043 ± 51.2 μg/g. SEM images of the samples revealed that hemicellulases hydrolyze the cell wall, leading to structure breakdown, which enabled [C8MIM]Br to have a high dissolving power for the targeted components. These factors are the main causes for the increasing in the total yield of the CPT and HCPT when using the ILEEE extraction method.

Ultrasound-assisted rapid extraction and kinetic modelling of influential factors: Extraction of camptothecin from Nothapodytes nimmoniana plant

Ultrasound-assisted extraction (UAE) of commercially important natural product camptothecin (CPT) from Nothapodytes nimmoniana plant has been investigated. The influences of process factors such as electric acoustic intensity, solid to liquid ratio, duty cycle, temperature and particle size on the maximum extraction yield and kinetic mechanisms of the entire extraction process have been investigated. The kinetics results showed that increasing the intensity, duty cycle, solid to liquid ratio and decreasing the particle size lead to substantial increase in extraction yields compared to classical stirring extraction. Different kinetic models were applied to fit the experimental data. The second order rate model appears to be the best. The extraction rate constant, initial extraction rate and the equilibrium concentration for all experimental conditions have been calculated. SEM analysis of spent plant material clearly showed hollow openings on cell structure, which could be directly correlated to explosive disruption by the action of ultrasound waves. Overall 1.7-fold increase in extraction yields of CPT (0.32% w/w) and decrease in time from 6h to 18min was observed over the stirring method.

Microwave assisted process intensification and kinetic modelling: Extraction of camptothecin from Nothapodytes nimmoniana plant

Process intensification of natural products extraction is possible through assistance of microwaves, ultrasound, high pressure, enzyme pretreatments and supercritical fluids. In the present paper microwave-assisted process intensification is investigated for the extraction of camptothecin (CPT) from Nothapodytes nimmoniana plant. CPT is an industrial raw material for the production of anticancer agents topotecan and irinotecan and semisynthetic analogs of CPT. Nothapodytes nimmoniana is found wild in India and is a prime source for CPT. Effects of various process factors such as stirring, solid to liquid ratio, microwave power, irradiation time and particle size on extraction kinetics have been studied. The results showed that stirring, microwave power and the temperature had a significant effect on extraction rate and yields of camptothecin. Overall process intensification has been achieved with extraction yield of 0.41% w/w of CPT, an efficiency of about 97% in very short time of just 2min as against 6h by classical string extraction method. Scanning electron microscopy (SEM) analysis of the spent plant material was performed to assess the effect of microwaves and found complete cell disruption has happened. This cell disruption and associated enhancement in mass transfer could be the prime reason for the process intensification. An attempt has been made to fit the extraction kinetics data with different kinetic models such as second order rate model, power law model and two site kinetic models. The second order rate model appears to be the best fit to explain the microwave assisted kinetics.

Molecularly imprinted polymers coated on carbon nanotubes for matrix solid phase dispersion extraction of camptothecin from Camptotheca acuminate

The protocol for the synthesis of MIPs.

Optimization of ultrasound-assisted extraction of camptothecin from Camptotheca acuminata seeds

Naturally occurring camptothecin (CPT) is an important source of chemotherapeutic agents. The extraction from Camptotheca acuminata is still the main approach to obtain CPT compared with total synthesis. In the present study, ultrasound-assisted extractions (UAE) of CPT from C. acuminata seeds with alkaline solutions were investigated and CPT yield were determined by High Performance Liquid Chromatography. The conditions of alkaline species and concentrations, extraction time, extraction temperature and ultrasonic power were optimized. Results show that both Na3PO4 and Na2CO3 solutions gain good extraction yields, whereas Na3PO4 solution has stronger basicity and need higher concentration than Na2CO3 solution does, thus aqueous Na2CO3 is more beneficial for the extraction. The optimal condition was ultrasonically extracted with 0.5% aqueous Na2CO3 at 50°C and ultrasonic power of 400 W for 60 min. Comparing with UAE with ethanol, the extraction with 0.5% Na2CO3 solution achieves higher yield. Moreover, aqueous Na2CO3 as a solvent has various advantages including non-toxicity, inflammable, non-corrosive and low cost, which ensure this UAE method is a superior method with high utilizing prospect.

Determination of camptothecin and 10-hydroxycamptothecin in human plasma using polymer monolithic in-tube solid phase microextraction combined with high-performance liquid chromatography

A biocompatible in-tube solid-phase microextraction (SPME) device was used for the direct and on-line extraction of camptothecin and 10-hydroxycamptothecin in human plasma. Biocompatibility was achieved through the use of a poly(methacrylic acid-ethylene glycol dimethacrylate) monolithic capillary column for extraction. Coupled to high performance liquid chromatography (HPLC) with UV detection, this on-line in-tube SPME method was successfully applied to the simultaneous determination of camptothecin and 10-hydroxycamptothecin in human plasma. The calculated detection limits for camptothecin and 10-hydroxycamptothecin were found to be 2.62 and 1.79 ng/mL, respectively. The method was linear over the range of 10-1000 ng/mL. Excellent method reproducibility was achieved, yielding RSDs of 2.49 and 1.59%, respectively. The detection limit (S/N = 3) of camptothecin was found to reach 0.1 ng/mL using fluorescence detection. The proposed method was shown to cope robustly with the extraction and analysis of camptothecin and 10-hydroxycamptothecin in plasma samples.

Comparison of techniques for the extraction of the anti-cancer drug camptothecin from Nothapodytes foetida

Extraction methods using stirring extraction, Soxhlet extraction, ultrasonic extraction and microwave-assisted extraction (MAE) were evaluated for the percentage extraction of camptothecin (CPT) and 9-methoxycamptothecin (9-Me-CPT) from Nothapodytes foetida. The extracts were analyzed by high performance liquid chromatography (HPLC). Methanol (90%, v/v) extracted high percentage extraction of CPT and 9-Me-CPT compared to ethanol (90%, v/v). The results shows that the percentage extraction of CPT and 9-Me-CPT from N. foetida by MAE was more efficient in short time followed by Soxhlet extraction, ultrasonic and stirring extraction methods. Maximum percentage extraction of CPT (2.67%, w/w) was obtained by MAE technique. MAE has need of 3 min, whereas ultrasonic extraction, Soxhlet extraction and stirring extraction techniques require 30, 120 and 30 min, respectively to leach higher percentage extraction of CPT and 9-Me-CPT. The times taken by the microwave extraction process was 40 times less than the Soxhlet extraction for percentage extraction of alkaloids. The present results show that the extraction efficiency and considerable saving of time by MAE was more competent than the other extraction techniques.