Over the past century, global use of water resources has increased sixfold due to population growth, economic development, and changing consumption patterns (UNESCO and UN-Water, 2020). Consequently, preserving water resources, referred to as the “blue gold” and a vital component of sustainable development, is widely recognized as essential. However, pharmaceutical pollution poses a significant threat to aquatic ecosystems and hinders progress towards at least 12 of the 17 Sustainable Development Goals (Domingo-Echaburu et al., 2021). To address this issue, the establishment of organizations monitoring pharmaceuticals in nature is urgently needed. Initiatives have emerged in several countries to introduce Environmental Risk Assessment (ERA) for pharmaceuticals (Jose et al., 2020) and to establish targeted eco-pharmacovigilance for selected pharmaceutical compounds including KTP (Wang et al., 2018). Below are the factors that determine the entry of KTP into the environment, primarily into aquatic ecosystems.

KTP is ubiquitously used in both human and veterinary medicine for treating pain, inflammation, and fever. KTP is weakly selective for cyclooxygenase isoenzymes (COX-1). The role of COX is to catalyze the formation of prostaglandins from arachidonic acid, which is released from membrane phospholipids upon activation of phospholipase A2 under various stimuli such as inflammatory, physical, chemical, and mitogenic conditions (Tomić et al., 2017). Consequently, KTP is prescribed for treating musculoskeletal disorders, including osteoarthritis and rheumatoid arthritis, and other conditions that cause pain and inflammation. It is also used to relieve mild to moderate pain, such as headaches, dental pain, menstrual cramps, and postoperative pain. In veterinary practice, KTP is used to reduce fever and inflammation in cattle (De Koster et al., 2022), postoperative rehabilitation of dogs (Monteiro et al., 2019; Ravuri et al., 2022), and even to treat injured sea turtles (Harms et al., 2021). Research is ongoing to study the efficacy of KTP for treating other animal species, leading to a wider application range of this drug (Hu et al., 2021; Reynolds et al., 2021). In addition, the drug is being studied for its use as a safe alternative to opioid analgesics (Doleman et al., 2021; Herzig et al., 2021; Pergolizzi et al., 2021). Thus, the volumes of production and consumption of KTP will only increase in the future. This is also facilitated by some stagnation of the pharmaceutical industry and drug shortages (Sharma et al., 2022). Thus, maintaining population health and extending healthy life expectancy is achieved by increasing the production and distribution of existing medications to the population (Mezzelani et al., 2018; Iijima et al., 2021; Locherty et al., 2021; Firdous et al., 2022).

Another factor to consider is the low rate of KTP decomposition and the inadequate efficiency of sewage treatment plants (Jureczko and Przystaś, 2018), resulting in the accumulation of KTP primarily in aquatic ecosystems (Chavoshani et al., 2020; Parolini, 2020; Mejías et al., 2021; Rastogi et al., 2021). KTP tends to accumulate in wastewater, especially hospital wastewater, due to its excretion from humans and animals in the form of metabolites, with only 1% of KTP being excreted unchanged (Kotwani et al., 2021). Moreover, there is a lack of sufficient methods for the proper removal, storage, and disposal of expired or unused KTP. Frequently, pharmaceuticals are flushed down the drain or disposed of in solid waste landfills because they are expired or no longer needed (Kleywegt et al., 2019; Petrie and Camacho-Muñoz, 2021; Rogowska and Zimmermann, 2022). Once KTP enters wastewater treatment plants (WWTPs), it can migrate into surface and groundwater because of poorly developed micropollutant removal technologies (Almeida et al., 2020; Rastogi et al., 2021).

In today’s world, the COVID-19 pandemic has also become a factor promoting a dramatic increase in NSAID concentrations in the environment. The efficacy of NSAIDs in alleviating pain and mitigating inflammatory symptoms associated with coronavirus disease 2019 has been a subject of considerable scientific investigation. Moreover, thorough assessments were conducted to assess the risks associated with the utilization of NSAIDs for this particular condition (Cumhur Cure et al., 2020; Robb et al., 2020; Kelleni, 2021). Certain NSAIDs proved to be effective in relieving COVID-19 symptoms without causing harm, but the long-term effects of taking anti-inflammatory drugs in conjunction with a viral infection remain unclear (Zhou et al., 2022). As a result of the global use of medications during the pandemic since the end of 2019, the detection of NSAIDs in aquatic systems has increased worldwide, with their concentrations ranging from a few nanograms to hundreds of micrograms per liter (Wojcieszyńska et al., 2022).

KTP has been detected in surface water (rivers, lakes, seas, oceans), wastewater (municipal, hospital, industrial), groundwater, and drinking water sources in over 30 countries worldwide (Table 1). Its global occurrence is evident, since trace amounts of KTP have been found in seawater in Antarctica (Szopińska et al., 2022). KTP concentrations are measured in the range of 0.16 ng/L (Italy, Turin, groundwater) to 260 μg/L (India, influent wastewater), with the highest concentration observed in India, where KTP is available over-the-counter. India, a major hub for drug manufacturing, also contributes to pharmaceutical waste discharge into aquatic ecosystems, with only 31% of wastewater undergoing pre-treatment (Philip et al., 2018; Praveenkumarreddy et al., 2021). In Africa, screening of KTP in water has only been conducted in South Africa (Supplementary Figure S1), leaving the extent of KTP contamination across most of the continent unknown (Waleng and Nomngongo, 2022). Similarly, limited research has been carried out in Australia regarding the detection of KTP: only a few sporadic investigations have been conducted so far (Świacka et al., 2022). The scarce data about these continents may be attributed to their predominantly arid landscapes, which receive less attention in terms of KTP detection studies. The focus of drug detection has primarily been on aquatic ecosystems, where the occurrence of KTP has been extensively investigated.

Upon examining the findings from studies on KTP detection, several noteworthy observations were revealed. The southern regions of India and Africa exhibited the highest levels of KTP pollution, with recorded concentrations reaching a maximum of 260,000 ng/L and 159,000 ng/L, respectively (Supplementary Figure S1). In Europe, significant concentrations were detected in specific locations, such as hospital wastewater in France (20,000 ng/L), influent wastewater in Southern Poland (10,700 ng/L), and surface water in the Czech Republic (6,500 ng/L) and Italy (5,150 ng/L). Studies conducted in the Americas are relatively limited, but higher concentrations were found in the effluent wastewater of Costa Rica (14,700 ng/L) and the surface waters of the Manus River in Brazil (14,215 ng/L). In Australia, increased concentrations of KTP were observed in the influent wastewater of Bega Valley, reaching 15,300 ng/L (Table 1).

It is important to note that certain WWTPs demonstrated better efficiency in the removal of KTP. As shown in Table 1, WWTPs incorporating activated sludge (AS, CAS, HRAS, and UASBR) exhibited the highest KTP removal rates, while WWTPs utilizing activated carbon showed the least efficient removal. These findings underscore the variability in treatment performance and highlight the importance of selecting appropriate treatment technologies for effective KTP removal in WWTPs.

In some countries, despite their similar geographic location, variations can be observed in the effectiveness of KTP removal from wastewater. These differences may be attributed to specific wastewater compositions, hydraulic retention times, redox conditions, loading on treatment plants, and filtration types employed (Wiest et al., 2018). Several studies reported fluctuations in KTP concentrations depending on the season during which the samples were collected (Barbosa et al., 2018; Česen et al., 2018; Aydin et al., 2019; Leiviskä and Risteelä, 2022). One possible reason for these fluctuations is the recurring exacerbations of rheumatoid arthritis and osteoarthritis that often occur during the winter and rainy seasons, resulting in an increased demand for KTP (Camacho-Muñoz et al., 2019).

Ecotoxicological studies aim at determining both acute and chronic toxicity of substances. Acute toxicity refers to harmful effects caused by a single or multiple exposures over a short period of time, often leading to a lethal outcome. Acute toxicity is typically expressed as either the median effective dose (ED₅₀) or the median lethal dose (LD₅₀). The ED₅₀ represents the concentration of exposure that produces a measurable effect in 50% of individuals in a population, while the LD₅₀ represents the lethal concentration that causes death in 50% of individuals. To evaluate the potential hazard of pharmaceutical pollutants to aquatic ecosystems, the Global Harmonized System of Classification and Labeling of Chemicals (GHS) is commonly used (United Nations, 2011). According to GHS, substances are classified into the following categories:

Based on the available data on acute toxicity and applying the GHS classification, KTP is classified as a compound that is hazardous to aquatic ecosystems (Table 2).

Chronic toxicity is an important aspect to consider when assessing the impact of pharmaceutical substances such as KTP on living organisms. Unlike acute toxicity, which focuses on short-term lethal effects, chronic toxicity examines the long-term effects of prolonged exposure to a stressor. Chronic toxicity is characterized by sublethal responses rather than immediate lethality (Parolini, 2020). The assessment of chronic toxicity involves determining the concentration without the observed effect (NOEC) or the lowest observed effect concentration (LOEC). These concentrations serve as criteria for evaluating chronic toxicity and help establish safe exposure levels. Chronic toxicity evaluation encompasses various aspects such as cytotoxicity (cellular damage), genotoxicity (damage to genetic material), disturbances in gene expression and metabolism, endocrine disruption (disruption of hormone systems), teratogenic effects (developmental abnormalities), morphological and tissue transformations, and behavioral changes (Świacka et al., 2021). Figure 1 summarizes the detrimental effects of KTP on several micro- and macroorganisms.

Fungi have been shown effective in removing xenobiotics due to the presence of low-specificity enzymes like peroxidases, laccases, and cellulases, which can modify and break down lignin. Ascomycetes and basidiomycetes often use the metabolic pathways of lignin degradation as a tool for the biological degradation of various targets, including pharmaceutical pollutants (Rastogi et al., 2021; Tormo-Budowski et al., 2021).

Among fungi, white-rot fungi have gained significant popularity in bioremediation efforts (Bulai et al., 2018; Sośnicka et al., 2022). Representatives of Trametes spp., Pleurotus spp., Phanerochaete spp., Irpex spp. have already proven themselves as promising biodegraders of pharmaceutical pollutants, including NSAIDs (Kum et al., 2009; Marco-Urrea et al., 2009, 2010; Hata et al., 2010; Rodarte-Morales et al., 2011; Nguyen et al., 2013; Sośnicka et al., 2022). In a study by Haroune et al. (2017), Trametes hirsuta IBB 450 degraded most (90%) of the 100 μg/L mixture of NSAIDs (acetaminophen, ibuprofen, indomethacin, KTP, mefenamic acid, and naproxen) within a 48-h experiment. The biodegradation of KTP was a multi-step process that involved uptake, intra- and extracellular transformation. The authors also proposed 10 products of KTP transformation (Figure 2), although further structural elucidation methods are required to confirm these proposed structures (Haroune et al., 2017).

Immobilization is often employed as an effective approach to accelerate and optimize the bioremediation of contaminants. Comparative experiments conducted by Tormo-Budowski et al. (2021) demonstrated that the use of immobilized Trametes versicolor strain ATCC 42530 on rice husks in fungal bioreactors, such as trickle-bed and stirred tank systems, increased the removal efficiency of 16 pharmaceuticals (1000 μg/L) from hospital wastewater. In a 336-h experiment, the stirred tank bioreactor removed approximately 54% of KTP, while the trickle-bed bioreactor with immobilized fungi removed over 99% of the pharmaceutical pollutant, with 73.3% being due to adsorption. Additionally, toxicological tests revealed a reduction in the toxicity of the treated wastewater after processing in the trickle-bed bioreactor (Tormo-Budowski et al., 2021).

In another study, Torán et al. (2017) found that the strain ATCC 42530, immobilized on wood granules in a fluidized bed bioreactor, was able to remove 80% of KTP (20 mg/L) from synthetic tap water over 31 days. The maximum loss of this NSAID was achieved on day 18 of the experiment in flocculated hospital wastewater. The authors concluded that immobilization on wood was an excellent strategy to maintain the high functional activity and survival of the fungus since pallet wood could be used as a specific source of nutrients. Based on these findings, the authors investigated the possibility of removing KTP in a packed-bed bioreactor under continuous mode of operation, and were able to achieve 80% KTP removal throughout the treatment (Torán et al., 2017).

White-rot fungi of the Pleurotus spp. were also found to express lignin-cellulolytic enzymes, primarily laccases, throughout their life cycle, making them promising biodegraders of pharmaceutical pollutants. In a study by Cruz-Ornelas et al. (2019), Pleurotus djamor ECS-0123 demonstrated the ability to degrade diclofenac, naproxen, and KTP individually and in mixtures. These NSAIDs were added to the medium individually at 10 mg/L or in a pharmaceutical mixture at 7 mg/L each. The results showed that after 48 h of incubation, the fungus eliminated 87% of KTP. However, in the presence of naproxen, the degradation of both drugs decreased even after an extended exposure time of 72 h, with 85% degradation for naproxen and 83% for KTP. Notably, the degradation of KTP in a combination with both diclofenac and naproxen was considerably effective, with 68 and 83% degradation observed after 6 and 48 h, respectively. The study also indicated that laccase activity increased by 25% with the addition of KTP and by 300% with the addition of the NSAID mixture (Cruz-Ornelas et al., 2019).

Pleurotus ostreatus, isolated from a decaying wood fruiting body, exhibited moderate activity in the degradation of NSAIDs (Palli et al., 2017). In a fluidized bed bioreactor using hospital wastewater, the partial degradation of KTP (10 mg/L) reached 36% within 48 h. With continuous input of hospital wastewater, the removal of KTP increased to 60% within 2 days and 70% within 15 days. Two KTP decomposition products were identified using NMR spectroscopy (see Figure 2): 2-[3-(4-hydroxybenzoyl)phenyl] propanoic acid and 2-[(3-hydroxy(phenyl)methyl)phenyl]-propanoic acid formed through hydroxylation of the aromatic ring and reduction of the keto group, respectively.

Dalecka et al. (2020) reported that Trametes versicolor DSM 6401, Trichoderma reesei DSM 768, Irpex lacteus IBB 104, Pleurotus ostreatus DSM 1020 and Fusarium solani (an environmental isolate from a pharmaceutical WWTP located in Riga, Latvia) removed diclofenac and KTP from synthetic wastewater. Trametes versicolor DSM 6401 removed KTP (5 mg/L) by more than 80% within 21 days, while other strains and their mixtures did not exhibit any activity towards KTP (Dalecka et al., 2020). In a later study, Trametes versicolor DSM 6401 and Aspergillus luchuensis (an isolate from a municipal WWTP located in Stockholm, Sweden) were used to remove KTP from urban wastewater in a fluidized bed pelleted bioreactor (Dalecka et al., 2021). The study showed that both fungi removed KTP (50 mg/L), achieving an over 90% removal rate. Furthermore, Trametes versicolor DSM 6401 and Aspergillus luchuensis accomplished the pharmaceutical removal through biosorption mechanisms, which could provide important biotechnological advantages by avoiding byproduct synthesis and minimizing energy costs.

When considering members of Ascomycota as potential degraders of pharmaceutical pollutants, Ledezma-Villanueva et al. (2022) isolated a strain of Cladosporium cladosporioides from sewage sludge that exhibited the ability to degrade KTP. The strain successfully eliminated 90% of KTP (100 μM) for 21 days. In a subsequent study, the authors constructed a pilot-scale two-stage mesophilic anaerobic digestion system to remove pharmaceutical pollutants from sewage sludge. They selected an artificial microbial consortium composed of the fungi Penicillium oxalicum XD-3.1, Penicillium raistrickii and Alternaria alternata, Cladosporium cladosporioides and the bacterium Micrococcus yunnanensis. This consortium eliminated 100 μM KTP within 10 days, resulting in the production of two nontoxic metabolites: (2-[(3-hydroxy(phenyl)methyl)phenyl]-propanoic acid and (3-ethylphenyl)(phenyl)methadone (Figure 2) (Angeles-de Paz et al., 2023).

Unfortunately, working with fungi for the elimination of pharmaceutical pollutants from natural environments can be ineffective. In a study by Olicón-Hernández et al. (2021), Penicillium oxalicum XD-3.1 was employed in a fluidized batch bioreactor to treat real hospital wastewater containing KTP. The results were discouraging as only a minimal reduction in KTP concentration was achieved. It is worth noting that the wastewater also contained other NSAIDs such as diclofenac, ibuprofen, mefenamic acid, and naproxen, along with various antibiotics. The initial concentration of KTP in the wastewater was 9455 ± 289 ng/L, and during the 96 h of the bioreactor operation, the XD-3.1 strain showed modest removal of KTP (2.6%). Additionally, Penicillium oxalicum XD-3.1 inhibited local fungal populations, including opportunistic human pathogens such as Mycosphaerella and Drechslera (Olicón-Hernández et al., 2021).

Although the utilization of fungi as biodegraders of KTP shows promise, further extensive studies are needed to fully explore the potential and limitations of this approach. Identification of degradation metabolites and evaluation of their toxicity will enhance our understanding of the efficacy and safety of employing fungi in the biodegradation of KTP and other pharmaceutical pollutants.

Bacteria are known for their ability to metabolize a broad spectrum of recalcitrant compounds and are preferred over fungi in biotechnological processes. This preference is largely due to bacteria’s non-mycelial growth, which mitigates concerns related to biomass accumulation on internal bioreactor surfaces (Tyumina et al., 2020). Currently, several documented studies have explored the use of both individual bacterial strains and microbial consortia for the removal of KTP. The utilization of individual bacterial cultures not only enables the complete elimination of pollutants but also facilitates the identification of biodegradation products and metabolic pathways. Furthermore, it allows for a detailed examination of the mechanisms governing the interaction between bacterial cells and pharmaceutical pollutants along with the identification of relevant bacterial adaptation mechanisms (Ivshina et al., 2019, 2021a,b).

In a study by Palyzová et al. (2018), the efficiency of bacterial degradation of several analgesic substances including codeine, diclofenac, ibuprofen, and KTP was examined. The researchers discovered that a gram-negative strain named Raoultella sp. KDF8, which was isolated from composted waste, exhibited the capability to degrade KTP (1 g/L) by approximately 60 ± 1.76% within a 96-h period at 28°C (Palyzová et al., 2018).

Through a large-scale screening of stress-tolerant actinomycetes from the Regional Specialized Collection of Alkanotrophic Microorganisms [acronym IEGM, the large-scale research facilities (USU) #73559, the core facilities (CKP) #480868, the World Federation for Culture Collections (WFCC) #285; http://www.iegmcol.ru], we identified Rhodococcus erythropolis IEGM 746 as a strain capable of degrading approximately 40% of 100 mg/L KTP withinn 14 days (Bazhutin et al., 2022). Respirometric analysis confirmed the high catalytic activity of rhodococci in the presence of KTP, while atomic force microscopy revealed morphometric changes in cells induced by the NSAID.

The use of bacterial consortia can increase the number of involved catabolic pathways, thereby enhancing the efficiency of removal and biodegradation of pharmaceutical pollutants and even leading to their complete mineralization (Wojcieszyńska et al., 2014; Tripathi et al., 2021). Ismail et al. (2016) investigated the potential of artificial consortia for removing KTP as the sole carbon source. They found that a consortium of strains, including Raoultella ornithinolytica B6, Pseudomonas aeruginosa JPP, Pseudomonas sp. P16 and Stenotrophomonas sp. 5LF 19TDLC, which were isolated from wastewater, could degrade KTP (5 μM) at a rate of 33 μg/h, achieving the complete removal within 48 h (Ismail et al., 2016). The bioconversion process resulted in the formation of three by-products: (3-ethylphenyl)(phenyl)methanone, (3-hydroxyphenyl)(phenyl)methanone, and (3-hydroxyphenyl)(oxo)acetic acid. Their structural formulas are presented in Figure 2.

In recent years, there has been a growing interest in a system that combines microalgae and bacteria due to its versatility. This approach not only enables the purification of wastewater but also helps to reduce the cost of aeration. Moreover, the biomass generated from this system can have various applications, including animal feed production and utilization in the medical, pharmaceutical, and industrial sectors (Wang et al., 2013). Building upon their previous research, Ismail et al. (2017) further investigated the potential of a consortium comprising bacterial biomass supplemented with the green microalgae Chlorella sp. Iso4. This consortium decomposed KTP at a rate of 3.5 μg/h for 10 days after a lag phase of approximately 24 h. Subsequently, the authors used the same technology in a photobioreactor and combined four gram-negative bacterial strains with microalgae to remove a mixture of KTP (0.5 mM), aspirin/salicylic acid (0.5 mM), and paracetamol (0.4 mM). Throughout the degradation period (28 days), p-aminophenol, an intermediate product of paracetamol, was observed. It is important to note that p-aminophenol is known to be mutagenic and toxic. However, this observation did not impede the nearly complete biodegradation (97%) of the NSAID cocktail within 4 days of hydraulic retention (Ismail et al., 2017).

The conventional methods used to evaluate the bacterial degradation potential, which rely on cultivation-based approaches, underestimate the extensive diversity present in natural ecosystems and hinder the understanding of complex microbial assemblages. Recognizing the significant influence of microbial activity, abundance, diversity, and community structure on bioremediation strategies, researchers have begun to focus more on the ability of natural microbial communities, particularly those found in WWTPs, to degrade pharmaceuticals and the changes they undergo when exposed to these compounds (Siles and Margesin, 2018; Bôto et al., 2021).

One area of research has focused on the metabolism of KTP by ammonia-oxidizing bacteria. In a study conducted in Kitakyushu, Japan, biomass was collected from an aerobic tank in a WWTP and then used in a membrane bioreactor to break down a range of targeted pharmaceuticals and personal care products (45 compounds) in two stages. In the first stage, nitrifying bacteria oxidized ammonia to nitrate, facilitating the cometabolism of certain pollutants through non-specific enzymes, such as ammonia monooxygenases. In the second stage, after ammonia consumption, the targeted compounds, including KTP, were degraded alongside endogenous respiration (decay) in the absence of external organic matter or ammonia. The study reported a KTP biodegradation rate coefficient of 1.713 L/g VSS (volatile suspended solids) day (Park et al., 2017).

In a recent study on the removal of KTP, a sulfur-driven autotrophic denitrification bioreactor was employed. The biotransformation of KTP (100 μg/L) occurred over a period of 120 days and was initiated by the restoration of the ketone group through a series of oxidation/reduction and hydroxylation reactions. This process resulted in the formation of five intermediate products (see Figure 2): (3-(1-hydroxyethyl)phenyl)(phenyl)methanone, (3-(1-hydroxyethyl)phenyl)(3-hydroxyphenyl)methanone, (3-hydroxyphenyl)phenyl)methanone, 2-(3-(carboxy(hydroxy)methylphenyl)propanoic acid, and 2-(3-(carbonylcarbonyl)phenyl)-3-hydroxypropanoic acid. Furthermore, Methyloversatilis, Methylotenera, and Hyphomicrobium were identified as the dominant genera involved in the process of KTP biotransformation, with an efficiency of 55.4% ± 0.7%. At lower initial concentrations of KTP (25 and 50 μg/L), complete degradation was achieved within 5 days (Huang et al., 2023).

In another study conducted by Escuder-Gilabert et al. (2018), activated sludge collected from the aerated tanks of municipal WWTPs in Valencia, Spain, was utilized for the bioconversion of racemic ibuprofen and KTP at concentrations of 100 mg/L each. The bacterial degradation of KTP was completed after 25 days of incubation. Chromatographic analysis showed similar peak areas and biodegradation values for both enantiomers, indicating that the biodegradation of KTP by microorganisms in this case was apparently not enantioselective (Escuder-Gilabert et al., 2018).

Membrane bioreactors are a well-established technology in water management for wastewater treatment and reuse. These systems offer advantages such as the production of high-quality effluent, compact footprint, and minimal sludge generation (Gurung et al., 2019). Membrane bioreactors integrate a biological process with membrane filtration, where biomass biodegradation occurs within the bioreactor tank, and the separation of treated wastewater from microorganisms takes place within a membrane module (Al-Asheh et al., 2021). In the context of KTP removal, membrane bioreactors have been successfully applied, achieving almost complete removal (97.4%) of KTP at concentrations of about 200 ng/L from real wastewater (Gurung et al., 2019).

Few studies have been conducted to investigate the removal of KTP under anaerobic conditions. In an anaerobic membrane bioreactor, the elimination of hydrophilic compounds, including KTP, was found to be low (up to 40%). However, the addition of biochar enhanced the removal process (Lei et al., 2022). Another study documented a low degree of KTP removal (<20%) in the sulfate-reducing bacteria sludge system (Jia et al., 2019). The use of anaerobic granular sludge systems did not result in any KTP removal (Faria et al., 2022). In a sulfidogenic fluidized bed bioreactor used to treat acidic metal-containing water and hospital wastewater, the rate of KTP removal was only 41.9% (Makhathini et al., 2021). In a separate study involving a two-stage mesophilic anaerobic digestion process (acidogenic and methanogenic, connected in series), the removal of KTP from wastewater was 53% (Gallardo-Altamirano et al., 2021). Interestingly, the relative abundance of the class Clostridia (Bacillota) as well as the families Propionibacteriaceae (Actinomycetota) and Cytophagaceae (Bacteroidota), and the versatile methanogenic genus Methanosarcina, showed strong correlations with the presence of KTP in the system.

Enzyme bioremediation is a process of using naturally occurring enzymes to break down and degrade pollutants in the environment. Laccases (EC 1.10.3.2) are multi-copper oxidoreductases that catalyze the oxidation of numerous persistent organic pollutants and have proven to be effective in degrading various pharmaceuticals, including ibuprofen, naproxen, and diclofenac (Yang et al., 2017). The use of laccases in pharmaceutical biodegradation is an eco-friendly and cost-effective solution for reducing the environmental impact of pharmaceutical residues. Furthermore, the biodegradation process facilitated by laccases is selective and specific, providing a targeted approach for removing pharmaceuticals from the environment.

Recent studies have focused on the immobilization of laccases to enhance their efficiency in biodegradation. A study by Apriceno et al. (2019) investigated the potential use of chitosan-immobilized laccases from the white-rot fungus Trametes versicolor for the biodegradation of commonly encountered micropollutants such as KTP, diclofenac, and naproxen. The research findings revealed that the use of a biocatalyst facilitated the removal of 23% of KTP (100 mg/mL) within 7 days.

A similar study was conducted using a microfilter composed of hollow polysulfone fibers with tyrosinases and laccases from Trametes versicolor for the removal of 14 pharmaceuticals (antibiotics, NSAIDs, etc.) in a novel hybrid bioreactor (Ba et al., 2018). The findings demonstrated that this system effectively eliminated most pharmaceutical pollutants, irrespective of the dominant removal mechanism, whether enzymatic or sorption-based. Specifically, for KTP (10 μg/L), a remarkable 95% transformation was achieved within 24 h. Although the precise mechanisms underlying the removal of KTP were not fully elucidated, the authors proposed that the bioreactor’s membrane may contribute to heterogeneous catalysis by adsorbing the targeted pharmaceuticals and other compounds from wastewater.

Another study showed that the oxidative activity of laccase towards KTP and aspirin (25 mg/L) increased through adsorption immobilization of the enzyme on date stones (Al-sareji et al., 2023). In addition to achieving nearly complete removal of the pharmaceuticals within 4 h, laccase exhibited high activity over several cycles. This study highlights the significance of recycling, particularly the use of agricultural waste as adsorbents in biotechnology.

A novel approach involved the development of biocatalytic membranes by incorporating commercially available cellulose membranes with oxidoreductase enzymes, including laccase, tyrosinase, and horseradish peroxidase. These membranes were utilized for the removal of micropollutants from real wastewater samples (Zdarta and Zdarta, 2022). The findings from the study revealed that the laccase-membrane system exhibited the highest efficacy in reducing KTP. Moreover, the catalysts developed in this study demonstrated promising characteristics for storage and reuse, underscoring their practical applicability and potential for sustainable use in water treatment processes.

Nevertheless, not all studies have yielded positive results regarding the efficiency of immobilized enzymes in removing KTP. For instance, Jahangiri et al. (2018) conducted a study where they employed electron beam irradiation to cross-link laccase derived from Phoma sp. UHH 5-1-03 onto polyvinylidene fluoride membranes. Unfortunately, both batch and continuous treatments for the removal of KTP (10 μM) from wastewater resulted in only 15 and 2% removal, respectively.

The degradation of KTP by microorganisms, including fungi and bacteria, has been extensively studied. Fungi, particularly white-rot fungi such as Trametes spp., Pleurotus spp., Phanerochaete spp., and Irpex spp., have shown effective degradation of KTP, either individually or in combination with other pharmaceutical pollutants. Isolated enzymes found in fungi, such as laccases with their high oxidation activity, can also be efficiently utilized. As for bacteria, they have exhibited less biodegradation activity. However, the use of gram-negative bacterial consortia can significantly enhance the rate of KTP biodegradation. Additionally, promising approaches such as immobilization techniques, bacterial consortia, and combinations with microalgae have shown potential in improving the removal efficiency of KTP.

Therefore, it is important to note that while there are effective methods for removing KTP from wastewater using whole-cell and enzyme biocatalysts, the potential formation of toxic byproducts should not be overlooked. This highlights the importance of not only finding efficient ways to remove micropollutants but also considering the potential environmental impact of the removal process itself. Ultimately, the pharmaceutical industry needs to implement more responsible disposal strategies to minimize the overall impact of these compounds on the environment.

In addition to biodegradation, sorption and adsorption technologies offer effective means of removing pharmaceutical pollutants from water. Sorption and adsorption technologies involve the physical binding of pharmaceutical contaminants to solid surfaces or materials. Common sorbent materials include algal biomass, activated carbon and other porous materials with high surface areas.

The application of adsorption processes, including biosorption, has shown a high potential for the eliminations of pharmaceuticals (Georgin et al., 2022). Although the use of algae for the removal of NSAIDs is a relatively new area of research, several studies have reported their effectiveness in addressing pharmaceutical contamination. In particular, macroalgae are mainly used to treat waste generated during pharmaceutical manufacturing since they serve as a carbon substrate for the formation of a porous and robust material, acting as an adsorbent (Boakye et al., 2019). For example, Ouasfi et al. (2019) investigated the biosorption of KTP from an aqueous solution using brown seaweed Laminaria digitata, which was collected in El Jadida on the West Atlantic coast of Morocco. The maximum adsorption capacity for KTP (150 mg/L) at 25°C and pH 3.4 was 443.45 mg/g, and its biosorption efficiency within 1 hour was 86.12% (Ouasfi et al., 2019).

Microalgae have also been explored for their potential in eliminating pharmaceutical pollutants. Hifney et al. (2021) conducted a study that specifically examined the use of Chlorella sp. cells for the adsorption of diclofenac (2.5 mg/L) and KTP (5 mg/L) from aqueous solutions. The Chlorella sp. culture used in the study was isolated from a polluted site in Assiut Governorate, Egypt. It is worth noting that the Chlorella genus is recognized for its high resistance to various stressful conditions. The study demonstrated that the adsorption of KTP onto the cells was initially slow, but it significantly increased over time as the contact time between the pharmaceutical compound and Chlorella sp. cells increased. Furthermore, over 75% of diclofenac and 60% of KTP were removed within 90 and 60 min, respectively. However, a gradual decrease in adsorption efficiency was observed thereafter due to the desorption phenomenon. This observation emphasized the significance of the contact time as a critical parameter in achieving optimal removal of xenobiotics and preventing the process of desorption over extended periods (Godos et al., 2009; Hifney et al., 2021).

Phytoremediation, also known as “plant-based remediation,” utilizes the natural abilities of plants to clean up the environment. Plants are capable of extracting, accumulating, and detoxifying the contaminants present in soil, air, and water through various physical, chemical, and biological processes.

Plant-assisted bioremediation of water contaminants is primarily utilized in constructed wetlands, which are water treatment systems that employ microbial communities, wetland plants, and natural soil processes to enhance water quality. In Tuscany, Italy, constructed wetlands planted with herbaceous species Phragmites australis (common reed) and trees Salix matsudana (willow) were used for removing nonylphenols and pharmaceuticals (atenolol, diclofenac, KTP, triclosan) from wastewater (Francini et al., 2018). The presence of both plants resulted in an over 80% removal efficiency of KTP. However, as noted by the authors, the removal of KTP from the water was due to its accumulation in the plants and sorption on gravel. In addition, the research demonstrated that KTP was absorbed by willow (125 ng/g) at greater levels compared to common reed (75 ng/g). Ren et al. (2023) investigated the removal of KTP in constructed wetlands under various saturation conditions, and the efficiency of KTP removal was 50–99.7%. Sánchez et al. (2022) constructed a pilot-scale system comprising a hybrid digester as the first step, a subsurface vertical flow constructed wetland as the second step with effluent recirculation, and a photodegradation unit as the third step/post-treatment. Using that system, KTP and other NSAIDs were completely removed (>99.5 %). The high effectiveness of KTP elimination from real wastewater using aerated constructed wetlands was also confirmed by Ávila et al. (2021).

Indeed, while adsorption and phytoaccumulation are effective in removing pharmaceutical pollutants, they may not eliminate all contaminants entirely. Other substances present in water can compete with pharmaceuticals for adsorption sites, potentially reducing the elimination efficiency. Adsorption itself is a non-selective process, meaning it does not specifically target particular pollutants but instead relies on the affinity between the adsorbent material and a wide range of molecules.

Furthermore, the bioaccumulation of xenobiotics in macrophytes can pose ecological risks, particularly if these plants are consumed by herbivores or if they decompose and release the accumulated compounds back into the environment. Additionally, the persistence of these compounds within plant tissues may limit the overall effectiveness of phytoremediation because bioaccumulated xenobiotics can remain in the system even after the macrophytes are harvested or decay.

To address these limitations, it may be useful to combine adsorption and bioaccumulation with other treatment techniques, such as biological degradation or advanced oxidation processes, to enhance the overall removal efficiency. By employing a multi-step approach, it becomes possible to target a broader spectrum of pollutants and achieve more comprehensive remediation of contaminated environments.