Natural and Synthetic Drugs Approached for the Treatment of Recurrent Aphthous Stomatitis Over the Last Decade.

Recurrent aphthous stomatitis (RAS) refers to a sore and frequently recurring inflammation of the oral tissues, distinguished by the presence of small ulcers that cause significant discomfort and cannot be attributed to any underlying disease. Different treatments have been used for RAS. This review aims to provide a comprehensive overview of the treatment options over the past decade for recurrent aphthous stomatitis (RAS), encompassing both natural and synthetic treatments. It will utilize clinical efficacy studies conducted in vivo and in vitro, along with a focus on the pharmaceutical approach through advancements in drug delivery development. We conducted a thorough literature search from 2013 to 2023 in prominent databases such as PubMed, Scopus, and Cochrane, utilizing appropriate keywords of recurrent aphthous stomatitis, and treatment. A total of 53 clinical trials with 3022 patients were included, with 35 using natural materials in their research and a total of 16 articles discussing RAS treatment using synthetic materials. All the clinical trials showed that natural and synthetic medicines seemed to benefit RAS patients by reducing pain score, ulcer size, and number of ulcers and shortening the healing duration.

Polymeric Nanohydrogel in Topical Drug Delivery System.

Nanohydrogels (NH) are biodegradable polymers that have been extensively studied and utilized for various biomedical applications. Drugs in a topical medication are absorbed via the skin and carried to the intended location, where they are metabolized and eliminated from the body. With a focus on their pertinent contemporary treatments, this review aims to give a complete overview of recent advances in the creation and application of polymer NH in biomedicine. We will explore the key features that have driven advances in nanotechnology and discuss the significance of nanohydrogel-based formulations as vehicles for delivering therapeutic agents topically. The review will also cover the latest findings and references from the literature to support the advancements in nanotechnological technology related to the preparation and application of NH. In addition, we will also discuss the unique properties and potential applications of NH as drug delivery systems (DDS) for skin applications, underscoring their potential for effective topical therapeutic delivery. The challenge lies in efficiently delivering drugs through the skin's barrier to specific areas with high control. Environmentally sensitive systems, like polymer-based NH, show promise in treating dermatological conditions. Polymers are pivotal in developing these drug delivery systems, with NH offering advantages such as versatile drug loading, controlled release, and enhanced skin penetration.

Alginate and Chitosan-Based Hydrogel Enhance Antibacterial Agent Activity on Topical Application.

Untreated topical infections can become chronic, posing serious health issues. Optimal skin adherence is crucial in addressing such infections. In this context, chitosan and alginate emerge as promising candidates for use as a foundation in the development of topical hydrogels. The aim of this review is to examine the literature on topical hydrogel formulations that use chitosan and alginate as foundations, specifically in the context of topical antibacterial agents. The research methodology involves a literature review by examining articles published in databases such as PubMed, Scopus, ScienceDirect, and Google Scholar. The keywords employed during the research were "Alginate", "Chitosan", "Hydrogel", and "Antibacterial". Chitosan and alginate serve as bases in topical hydrogels to deliver various active ingredients, particularly antibacterial agents, as indicated by the search results. Both have demonstrated significant antibacterial effectiveness, as evidenced by a reduction in bacterial colony counts and an increase in inhibition zones. This strongly supports the idea that chitosan and alginate could be used together to make topical hydrogels that kill bacteria that work well. In conclusion, chitosan and alginate-based hydrogels show great potential in treating bacterial infections on the skin surface. The incorporation of chitosan and alginate into hydrogel formulations aids in retaining antibacterial agents, allowing for their gradual release over an optimal period. Therefore, hydrogels specifically formulated with chitosan and alginate have the potential to serve as a solution to address challenges in the treatment of topical bacterial infections.

Nanosuspension-Based Drug Delivery Systems for Topical Applications.

Nanosuspensions have garnered recent attention as a promising strategy for mitigating the bioavailability challenges of hydrophobic drugs, particularly those characterized by poor solubility in both aqueous and organic environments. Addressing solubility issues associated with poorly water-soluble drugs has largely resolved the need to enhance drug absorption and bioavailability. As mucosal formulations and topical administration progress in the future, nanosuspension drug delivery, straightforward formulation techniques, and versatile applications will continue to be subjects of interest. Nanosuspensions have undergone extensive scrutiny in preparation for topical applications, encompassing ocular, pulmonary, and dermal usage. Among the numerous methods aimed at improving cutaneous application, nanocrystals represent a relatively recent yet profoundly intriguing approach. Despite the increasing availability of various nanosuspension products, primarily designed for oral administration, only a limited number of studies have explored skin permeability and drug accumulation in the context of nanosuspensions. Nevertheless, the scant published research unequivocally underscores the potential of this approach for enhancing cutaneous bioavailability, particularly for active ingredients with low to medium solubility. Nanocrystals exhibit increased skin adhesiveness in addition to heightened saturation solubility and dissolution rate, thereby augmenting cutaneous distribution. The article provides a comprehensive overview of nanosuspensions for topical application. The methodology employed is robust, with a well-defined experimental design; however, the limited sample size raises concerns about the generalizability of the findings. While the results demonstrate promising outcomes in terms of enhanced drug delivery, the discussion falls short of addressing certain limitations. Additionally, the references largely focus on recent studies, but a more diverse inclusion of historical perspectives could offer a more holistic view of the subject.

Efficacy and safety of casirivimab-imdevimab combination on COVID-19 patients: A systematic review and meta-analysis randomized controlled trial.

Background: The advantages and disadvantages of casirivimab-imdevimab for coronavirus disease 2019 are not well understood. We conducted a systematic review and meta-analysis of relevant literature to determine the therapeutic effectiveness and potential side effects of casirivimab-imdevimab in COVID-19 patients. Methods: Databases were searched from the time of their commencement until February 28th, 2023. The primary results evaluated were the death rate at 28 days, progression of current clinical symptoms within 28 days, viral load, discharge from hospital, and any adverse events. Also, we contrasted the effects of the casirivimab-imdevimab treatment with placebo or standard of care. The protocol registration for this systematic review and meta-analysis was recorded in the PROSPERO database (CRD42023412835). Results: A total of eight studies were included, comprising 19,819 patients, and conducted a qualitative assessment of their risk of bias using the Cochrane risk of bias tool. Casirivimab-imdevimab effectively reduced the mortality rate (OR = 0.62; 95 % CI of 0.40-0.98; p = 0.04; I2 = 30 %) and reduced the progression of clinical symptoms (OR = 0.86; 95 % CI of 0.79-0.93; p = 0.0003; I2 = 57 %). Casirivimab-imdevimab also improved viral load clearance and hospital discharge. Additionally, the trials' findings demonstrated a slight decrease in the likelihood of adverse events occurring with the use of casirivimab-imdevimab. Conclusion: Our research suggests that casirivimab-imdevimab may be a valuable, safe, and effective anti-SARS-CoV-2 regimen.

Knowledge, Perception, and Readiness of Indonesian Pharmacists for the Implementation of Telepharmacy-Based Pharmaceutical Services in Indonesia.

Background: Telepharmacy, a digital technology-driven approach, has emerged as a potential solution to address the challenges posed by this pandemic. Telepharmacy is a method used in pharmaceutical practice where a pharmacist utilizes telecommunications technology to supervise aspects of pharmacy operations or provide patient care services. This study aimed to assess pharmacists' level of knowledge, perception, and readiness toward telepharmacy in Indonesia. Methods: A cross-sectional approach was used in this study, and non-probabilistic purposive sampling technique was used to select respondents who were Indonesian pharmacists. The Telepharmacy Knowledge, Perception, and Readiness questionnaire, translated into Indonesian and administered online, was used to measure the pharmacist's knowledge, perception, and readiness level. Descriptive and inferential data analyses were performed using SPSS version 26, with a p-value of ≤0.05 considered statistically significant. Results: A total of 378 responses were obtained, with 96.83% exhibiting high knowledge and 63.23% showing high readiness for telepharmacy services. Furthermore, 58.20% of respondents had a positive perception of telepharmacy services. The results indicate a significant influence of pharmacist's knowledge and perception on their readiness to implement telepharmacy services in the future practice. Conclusion: Most study participants had sufficient knowledge, positive perceptions, and readiness to implement telepharmacy services in their future pharmaceutical practice. However, they expressed concerns about the potential for an increased workload and the potential lack of incentives associated with the widespread adoption of telepharmacy practice models. Telepharmacy practice models must be included in the training programs that train future's pharmacists in order to ensure that they have the abilities required to offer telepharmacy services.

Ulvan/Silver nanoparticle hydrogel films for burn wound dressing.

Ulvan is a polysaccharide from green algae that shows good hydrogel film dressing characteristics. Silver nanoparticles (AgNP) can be incorporated into the hydrogel film to improve antibacterial properties and provide a potential burn treatment. In this study, we developed a novel hydrogel film wound dressing composed of ulvan and silver nanoparticles. Two concentrations (0.5 mM and 1 mM) of silver nitrate were used to produce ulvan-silver nanoparticles hydrogel film (UHF-AgNP0.5 and UHF-AgNP1), respectively. The physicochemical characteristics of the hydrogel films were evaluated, including particle size, zeta potential, Fourier transform infrared (FTIR), X-ray diffractometry (XRD), scanning electron microscope and energy-dispersive X-ray (SEM-EDX). Furthermore, the in vitro antimicrobial activity, and second-degree burn wound healing test were evaluated. The UHF-AgNP0.5 showed the highest antimicrobial activity compared to UHF-AgNP1 and UHF film. Meanwhile, an in vivo study using Wistar rats induced second-degree burns showed that UHF-AgNP0.5 significantly accelerated the healing process by regulating the inflammatory process, increasing re-epithelialization, and improving the vascularization process. Ulvan-silver nanoparticle hydrogel films have the ability to accelerate the healing of second-degree burns and are potential candidates for wound dressings.

Application, Benefits, and Limitations of Telepharmacy for Patients with Diabetes in the Outpatient Setting.

After the COVID-19 pandemic, telepharmacy has become increasingly widely used as an alternative to pharmaceutical care by remote pharmacists. Patients with diabetes mellitus are one of the patients who get benefit the most from telepharmacy practices, which allow patients to consult without meeting face to face and minimize the risk of virus transmission. The authors conduct an assessment of the benefits and limitations of using telepharmacy that are used throughout the world and then hopes that they can become a reference in the development of telepharmacy in the future. A total of 23 relevant articles were used for analysis in this narrative review after searching for articles in three sources, including PubMed, Google Scholar and ClinicalTrials.gov, until October 2022. This narrative review shows that telepharmacy plays an important role in improving clinical outcomes, patient therapy adherence and reduce the number of patient visit and hospitalization, but telepharmacy also has limitations in its use related to security and privacy, as well as pharmacist intervention that has not been maximized. However, telepharmacy has great potential to facilitate diabetes mellitus patients in pharmaceutical services.

Hyaluronic Acid-Coated Chitosan Nanoparticles as an Active Targeted Carrier of Alpha Mangostin for Breast Cancer Cells.

Alpha mangostin (AM) has potential anticancer properties for breast cancer. This study aims to assess the potential of chitosan nanoparticles coated with hyaluronic acid for the targeted delivery of AM (AM-CS/HA) against MCF-7 breast cancer cells. AM-CS/HA showed a spherical shape with an average diameter of 304 nm, a polydispersity index of 0.3, and a negative charge of 24.43 mV. High encapsulation efficiency (90%) and drug loading (8.5%) were achieved. AM released from AM-CS/HA at an acidic pH of 5.5 was higher than the physiological pH of 7.4 and showed sustained release. The cytotoxic effect of AM-CS/HA (IC50 4.37 µg/mL) on MCF-7 was significantly higher than AM nanoparticles without HA coating (AM-CS) (IC50 4.48 µg/mL) and AM (IC50 5.27 µg/mL). These findings suggest that AM-CS/HA enhances AM cytotoxicity and has potential applications for breast cancer therapy.

Apocynin-loaded PLGA nanomedicine tailored with galactosylated chitosan intrigue asialoglycoprotein receptor in hepatic carcinoma: Prospective targeted therapy.

Nature serves as a priceless source for phytomedicines to treat different types of cancer, including hepatocellular carcinoma (HCC). Apocynin (APO), an anti-cancer phytomedicine, is a particular nicotinamide adenine dinucleotide phosphate-oxidase (NADPH-oxidase) inhibitor, which has recently dawned for its multilateral pharmacological activities. As far as we are aware, no investigation has been carried out yet to develop a targeted-nanostructured delivery system of APO to HCC. Consequently, chitosan derivative with galactose groups namely; galactosylated chitosan (GC), particularly recognized by the asialoglycoprotein receptor (ASGR), was synthesized and its chemical structure was thoroughly characterized by substantial techniques. Afterwards, GC-coated nanoplatform for hepatocyte attachment "APO-loaded galactosylated chitosan-coated poly(d,l-lactide-co-glycolide) nanoparticles (APO-loaded GC-coated PLGA NPs)" was developed. The prosperous APO-loaded GC-coated PLGA NPs would be comprehensively appraised through extensive investigations. Their solid state characterization using Fourier transform-infrared spectroscopy, powder X-ray diffraction, and differential scanning calorimetry proved APO's encapsulation in the polymeric matrix. Transmission electron microscopy imaging of the investigated NPs highlighted their spherical architecture with a nanosized range and a characteristic halo-like appearance traceable to the GC coating of the NPs' surface. Saliently, the results of in vitro cytotoxicity screening revealed the spectacular anti-cancer efficacy of APO-loaded GC-coated PLGA NPs formula against the HepG2 cell line. Moreover, the fluorescence microscope disclosed the distinguished cellular uptake of such formula via ASGPR mediated endocytosis. Inclusively, a multifunctional nano-phytomedicine delivery system with a promising active hepatocyte-targeting, effective uptake into HepG2 cells, and sustained drug release pattern was successfully developed.

A Review of Coformer Utilization in Multicomponent Crystal Formation.

Most recently discovered active pharmaceutical molecules and market-approved medicines are poorly soluble in water, resulting in limited drug bioavailability and therapeutic effectiveness. The application of coformers in a multicomponent crystal method is one possible strategy to modulate a drug's solubility. A multicomponent crystal is a solid phase formed when several molecules of different substances crystallize in a crystal lattice with a certain stoichiometric ratio. The goal of this review paper is to comprehensively describe the application of coformers in the formation of multicomponent crystals as solutions for pharmaceutically active ingredients with limited solubility. Owing to their benefits including improved physicochemical profile of pharmaceutically active ingredients, multicomponent crystal methods are predicted to become increasingly prevalent in the development of active drug ingredients in the future.

Stabilization and Movable Ligand-Modification by Folate-Appended Polyrotaxanes for Systemic Delivery of siRNA Polyplex.

To achieve a systemic targeted delivery of siRNA using polymeric carriers, there is a dilemma between ligand modification and stabilization of the polyplex. Namely, ligand modification often leads to destabilization of the polyplex in the blood circulation. In fact, we previously developed cyclodextrin (CD)/polyamidoamine dendrimer conjugates (CDE) as siRNA carriers, and the interaction of CDE/siRNA was decreased by the conjugation with folate-polyethylene glycol, leading to the destabilization. To overcome this dilemma, in this study, folate-appended polyrotaxanes (Fol-PRX) were developed. Fol-PRX stabilized CDE/siRNA polyplex by intermolecularly connecting CDE molecules through a host-guest interaction between adamantane at the terminals of Fol-PRX and ß-CD in the polyplex. Moreover, the intermolecular connection of the polyplex with Fol-PRX provided movable folate moieties on the surface. As a result, Fol-PRXs enhanced the in vivo antitumor activity of the polyplex after intravenous administration, suggesting their utility as the dual-functional materials for systemic delivery of siRNA polyplexes.

Monoclonal antibody as a targeting mediator for nanoparticle targeted delivery system for lung cancer.

Lung cancer is the second most common type of cancer after breast cancer. It ranks first in terms of mortality rate among all types of cancer. Lung cancer therapies are still being developed, one of which makes use of nanoparticle technology. However, conjugation with specific ligands capable of delivering drugs more precisely to cancer sites is still required to enhance nanoparticle targeting performance. Monoclonal antibodies are one type of mediator that can actively target nanoparticles. Due to the large number of antigens on the surface of cancer cells, monoclonal antibodies are widely used to deliver nanoparticles and improve drug targeting to cancer cells. Unfortunately, these antibodies have some drawbacks, such as rapid elimination, which results in a short half-life and ineffective dose. As a result, many of them are formulated in nanoparticles to minimize their major drawbacks and enhance drug targeting. This review summarizes and discusses articles on developing and applying various types of monoclonal antibody ligand nanoparticles as lung cancer target drugs. This review will serve as a guide for the choice of nanoparticle systems containing monoclonal antibody ligands for drug delivery in lung cancer therapy.

Alginate/Chitosan-Based Hydrogel Film Containing α-Mangostin for Recurrent Aphthous Stomatitis Therapy in Rats.

Recurrent aphthous stomatitis (RAS) is a prevalent clinical disorder that causes mouth ulcers. Furthermore, corticosteroid treatment has been widely utilized for RAS therapy; however, it has side effects on the oral mucosa that limit its application. This study aimed to develop a novel RAS therapy with the natural ingredient α-mangostin, delivered by alginate and chitosan polymers-based hydrogel film (α-M Alg/Chi-HF). To prepare α-M Alg/Chi-HF, the solvent evaporation and casting methods were used, then characterized by using SEM, FTIR, and XRD. Based on the characterization studies, the α-M in α-M/EtOH Alg/Chi-HF with ethanol (EtOH) was found to be more homogenous compared to α-M in Alg/Chi-HF with distilled water (H2O) as a casting solvent. The in vitro viability study using NIH3T3 cells showed 100% viability of α-M Alg/Chi-HF (EtOH) and Alg/Chi-HF after 24 h incubation, indicating well tolerability of these hydrogel films. Interestingly, the in vivo studies using male white rats (Rattus norvegicus Berkenhout) proved that α-M/EtOH Alg/Chi-HF with a recovery of 81.47 ± 0.09% in seven days significantly more effective RAS therapy compared to control. These results suggest that α-M/EtOH Alg/Chi-HF has the potential as an alternative for RAS therapy.

Chitosan-Hyaluronic Acid Nanoparticles for Active Targeting in Cancer Therapy.

Cancer is the most common cause of death worldwide; therefore, there is a need to discover novel treatment modalities to combat it. One of the cancer treatments is nanoparticle technology. Currently, nanoparticles have been modified to have desirable pharmacological effects by using chemical ligands that bind with their specific receptors on the surface of malignant cells. Chemical grafting of chitosan nanoparticles with hyaluronic acid as a targeted ligand can become an attractive alternative for active targeting. Hence, these nanoparticles can control drug release with pH- responsive stimuli, and high selectivity of hyaluronic acid to CD44 receptors makes these nanoparticles accumulate more inside cells that overexpress these receptors (cancer cells). In this context, we discuss the benefits and recent findings of developing and utilizing chitosan-hyaluronic acid nanoparticles against distinct forms of cancer malignancy. From here we know that chitosan-hyaluronic acid nanoparticles (CHA-Np) can produce a nanoparticle system with good characteristics, effectiveness, and a good active targeting on various types of cancer cells. Therefore, this system is a good candidate for targeted drug delivery for cancer therapy, anticipating that CHA-Np could be further developed for various cancer therapy applications.

Polymeric Hydrogels as Mesenchymal Stem Cell Secretome Delivery System in Biomedical Applications.

Secretomes of mesenchymal stem cells (MSCs) have been successfully studied in preclinical models for several biomedical applications, including tissue engineering, drug delivery, and cancer therapy. Hydrogels are known to imitate a three-dimensional extracellular matrix to offer a friendly environment for stem cells; therefore, hydrogels can be used as scaffolds for tissue construction, to control the distribution of bioactive compounds in tissues, and as a secretome-producing MSC culture media. The administration of a polymeric hydrogel-based MSC secretome has been shown to overcome the fast clearance of the target tissue. In vitro studies confirm the bioactivity of the secretome encapsulated in the gel, allowing for a controlled and sustained release process. The findings reveal that the feasibility of polymeric hydrogels as MSC -secretome delivery systems had a positive influence on the pace of tissue and organ regeneration, as well as an enhanced secretome production. In this review, we discuss the widely used polymeric hydrogels and their advantages as MSC secretome delivery systems in biomedical applications.

α-Mangostin/γ-Cyclodextrin Inclusion Complex: Formation and Thermodynamic Study.

α-Mangostin (α-M) has various biological activities, such as anti-cancer, antibacterial, anti-fungal, anti-tyrosin, anti-tuberculosis, anti-inflammatory, and antioxidant. However, it has very low solubility in water. The formulation of this compound requires high amounts of solubilizers, which limits its clinical application. In addition, its low solubility in water is a barrier to the distribution of this drug, thus affecting its potency. Cyclodextrin (CD) is widely used as a solubility enhancer of poorly soluble drugs. This study aimed to increase the solubility of α-M in water through complex formation with CD. The complex of α-Mangostin and γ-Cyclodextrin (α-M/γ-CD CX) was prepared by the solubilization method, resulting in a solubility improvement of α-M in water. Characterization of α-M/γ-CD CX by using FTIR-Spectrometry, XRD, H-, C-, and HMBC-NMR showed that α-M was able to form an inclusion complex with γ-CD. The complex yielded an entrapment efficiency of 84.25 and the thermodynamic study showed that the α-M/γ-CD CX was formed spontaneously, based on the negative values of Gibbs energy and ΔH. Interestingly, the solubility of α-M/γ-CD CX significantly increased by 31.74-fold compared with α-M. These results suggest that α-M/γ-CD CX has the potential in the formulation of water-based preparation for clinical applications.

A Comprehensive Review on Ulvan Based Hydrogel and Its Biomedical Applications.

Ulvan is a natural sulfated polysaccharide obtained from marine green algae composed of 3-sulfated rhamnoglucuronan as the main component. It has a unique chemical structure that rich of L-rhamnosa, D-glucuronic acid, and L-iduronic acid. Ulvan has a similar structure to glycosaminoglycans (GAGs) in mammals including chondroitin sulfate, dermatan sulfate, and heparan sulfate that has broad range applications for many years. Here, we provide an overview of ulvan based hydrogels for biomedical applications. Hydrogels are one of ulvan advances in polymer science for application in drug delivery, tissue engineering, and wound healing. This review presented an overview about functional information of ulvan based hydrogels and the promising potential in biomedicals collected from published papers in Scopus, PubMed, and Google Scholar. Other important aspects concerning properties, hydrogel-forming mechanisms, and ulvan based hydrogel developments were reported as well. As conclusion, ulvan showed interesting properties in forming hydrogels and promising advances in biomedical applications.

Improvement of Pharmaceutical Properties of Zerumbone, a Multifunctional Compound, Using Cyclodextrin Derivatives.

Zerumbone is a multifunctional compound which shows various biological activities, such as antitumor activity, anti-inflammatory activity, antiulcer activity, etc. However, to use Zerumbone as functional foods or medicines, its pharmaceutical properties such as solubility should be improved. In the present study, we prepared its inclusion complexes with various cyclodextrin (CyD) derivatives, and evaluated their solubility, release profile of the drug and cytotoxic activity. Among 11 CyDs, sulfobutylether (SBE)-ß-CyD showed the highest solubilizing effect for Zerumbone. Phase solubility diagrams of SBE-ß-CyD/Zerumbone in 10% methanol solution showed AL type, and the stability constant was 756 M-1. SBE-ß-CyD also formed the solid complex with Zerumbone by kneading for 90 min. Importantly, the dissolution rate of Zerumbone was improved by complexation with SBE-ß- and hydroxypropyl (HP)-ß-CyDs, and its supersaturation was maintained for several hours. The solubilizing effects by SBE-ß-CyD was greater than that of HP-ß-CyD. Moreover, SBE-ß-CyD/Zerumbone complex also retained the cytotoxic activity of Zerumbone. These results suggest that CyDs, especially SBE-ß-CyD, were useful to improve the solubility of Zerumbone.

Dual targeting system by supramolecular complex of folate-conjugated methyl-ß-cyclodextrin with adamantane-grafted hyaluronic acid for the treatment of colorectal cancer.

In our previous study, we demonstrated that folate-appended methyl­ß­cyclodextrin (FA-M-ß-CyD) was a promising antitumor agent for the treatment of folate receptor-α (FR-α)-expressing tumors. In the present study, to enhance the antitumor effect of FA-M-ß-CyD against FR-α- and CD44-expressing colorectal cancer cells, we synthesized a dual targeting supramolecular complex composed of FA-M-ß-CyD and adamantane-grafted hyaluronic acid (Ad-HA). The supramolecular complex of Ad-HA/FA-M-ß-CyD showed higher cytotoxic activity in HCT116 cells (FR-α (+), CD44 (+)), a human colon cancer cell line, than FA-M-ß-CyD alone. In addition, the cytotoxic activity of Ad-HA/FA-M-ß-CyD was significantly impaired by the addition of FA and HA, as inhibitors of FR-α and CD44, respectively. Furthermore, tetramethylrhodamine isothiocyanate (TRITC)-labeled FA-M-ß-CyD was efficiently internalized into HCT116 cells through supramolecular complexation with Ad-HA, compared to that of TRITC-FA-M-ß-CyD alone. Additionally, Ad-HA/FA-M-ß-CyD induced mitophagy in HCT116 cells. These results suggest that Ad-HA/FA-M-ß-CyD targeted HCT116 cells, as well as induced mitophagy-mediated cell death. Notably, an intravenous injection of the Ad-HA/FA-M-ß-CyD complex in a mouse model of colorectal cancer significantly ameliorated the growth of tumor polyps. Collectively, these results suggest that Ad-HA/FA-M-ß-CyD has antiproliferation effects in tumors, based on the dual targeting activity.