Abstract
Background/Aim: Peritoneal metastasis is associated with poor prognosis and low response rates to systemic chemotherapy due to multidrug resistance. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has improved local drug delivery but remains limited by uneven drug distribution, with most aerosol deposition concentrated opposite the nozzle. To overcome this, rotational intraperitoneal aerosol chemotherapy (RIPAC) was developed. This study aimed to design a universal electric medical clamp enabling stable nozzle rotation for RIPAC.
Materials and Methods: A prototype device was constructed using a miniaturized electric motor mounted within a modular clamp to induce conical pendulum motion of the aerosol nozzle. Iterative design optimizations addressed instability and vibration, evolving from simple fixed joints to reinforced mechanical assemblies and finally a hydraulic joint system. Prototypes were evaluated in benchtop and porcine models for motion stability, spray uniformity, and mechanical robustness under operative conditions.
Results: The initial mockup device achieved pendulum-like motion but failed to maintain stability during in vivo testing due to shifts in the nozzle’s center of gravity and joint collapse. Reinforced joint designs improved stability but required cumbersome adjustments. The final hydraulic joint-integrated clamp provided enhanced fixation strength, increased degrees of freedom, and smoother fine-tuned positioning, while accommodating motor load. This configuration enabled consistent nozzle motion with greater clinical feasibility.
Conclusion: A universal electric medical clamp was successfully developed for RIPAC, providing stable rotational motion and improved drug distribution potential compared with PIPAC. This innovation lays the groundwork for clinical translation of RIPAC as a promising strategy to enhance intraperitoneal chemotherapy efficacy.
- Peritoneal metastasis
- pressurized intraperitoneal aerosol chemotherapy
- rotational intraperitoneal aerosol chemotherapy
- universal electric medical clamp
- drug distribution
Introduction
Peritoneal metastasis is associated with extremely poor prognosis worldwide, and the response rates of systemic chemotherapy for multidrug-resistant peritoneal metastasis from ovarian, gastric and colorectal cancer remain disappointingly low, approximately ranging from 10% to 20% (1-3). This is mainly attributed to mechanisms such as drug efflux transporters that actively remove cytotoxic agents even in the presence of adequate drug concentrations in the tissue (4).
Historically, high-dose chemotherapy combined with autologous bone marrow or stem cell transplantation was attempted to increase intratumoral drug concentrations by transiently suppressing the bone marrow, but although response rates improved modestly, survival benefits were limited and severe adverse events including life-threatening myelosuppression and infection led to discontinuation of this approach in clinical practice (5, 6).
A new avenue in overcoming these limitations has been the intraperitoneal drug-delivery approach using pressurized intraperitoneal aerosol chemotherapy (PIPAC). PIPAC is a novel intraperitoneal drug-delivery method in which approximately 10% of the standard intravenous dose of chemotherapy is diluted in 50-200 ml of 0.9% normal saline. Using a high-pressure injector, the solution is then aerosolized via a specially designed nozzle inserted through a laparoscopic system at a pressure of 200 psi and a flow rate of 0.5-0.6 ml/s. The aerosolized chemotherapy is distributed throughout the peritoneal cavity while maintaining a capnoperitoneum of 12 mmHg for 30 min, allowing deep penetration of the agent to peritoneal surfaces and resulting in a dramatic increase in local tissue drug concentrations, thereby enhancing the antitumor response, reaching 61 to 65% (3, 7).
However, PIPAC also has technical limitations: over 90% of the aerosolized drug is deposited on tissue surfaces directly opposite the nozzle, while only 10% or less reaches more remote areas of the abdominal cavity. This uneven distribution has been demonstrated in both ex vivo and in vivo studies, revealing drug penetration depths of up to 300 μm at the primary impact site, but only 100 μm in areas outside of the principal spray direction, highlighting an urgent need for device or technique refinement to ensure homogenous drug delivery across the peritoneum (8-10).
To overcome this limitation, we developed the rotational intraperitoneal pressurized aerosol chemotherapy (RIPAC) system (11, 12). Our preclinical studies demonstrated that RIPAC can increase both tissue concentration and drug penetration depth by 1.5- to 3-fold compared with conventional PIPAC (11). For RIPAC, achieving a conical pendulum trajectory of the nozzle while maintaining secure fixation of the device is crucial for optimal drug distribution. Therefore, in this study, we aimed to develop a universal electric medical clamp specifically designed to enable the safe and effective implementation of the RIPAC system.
This study focused on device development; the suitability of the nozzle’s conical pendulum motion and the detachment aspect were evaluated using a laparoscopic system. Size evaluation for aerosols corresponding to the nozzle used in this study was reported elsewhere (13).
Materials and Methods
Prototype development and mockup testing. To implement a novel RIPAC system capable of generating conical pendulum motion, we first developed a proof-of-concept mockup device. The initial prototype consisted of a miniaturized electric motor connected to a custom-mounting assembly designed to securely hold and rotate a standard aerosolization nozzle. The motor was selected based on its ability to generate controlled rotational speeds and torques compatible with clinical laparoscopy settings and was integrated into a modular housing to facilitate iterative design modifications.
The mounting assembly was engineered to allow precise adjustment of rotational angles and to maintain the nozzle’s spatial stability during conical pendulum motion. Initial mockup devices were fabricated using medical-grade plastics and stainless steel, compliant with biocompatibility and sterilization requirements. For all in vivo tests, the nozzle’s rotational speed was pre-set at 300-500 revolutions per minute (rpm), a range demonstrated in previous animal studies to avoid mechanical injury to visceral organs while maintaining effective aerosol distribution.
The assembled system was evaluated using a pig model to assess: (i) the effective generation of conical pendulum trajectories, (ii) the uniformity of aerosolized drug distribution, and (iii) mechanical stability under simulated operative conditions. During in vivo testing, the conical pendulum motion of the nozzle was confirmed using a laparoscopic camera system. Mechanical stability was evaluated by monitoring the nozzle’s rpm and positional deviation during operation under standard intra-abdominal pressure (12 mmHg CO2). For the test, we used one pig in a preclinical study, which was approved by the Institutional Animal Care and Use Committee of CRONEX (No. 202502002).
Iterative design optimization. Based on the outcomes of the initial tests, mechanical instabilities and sources of vibration were identified, particularly during conical pendulum motion. These instabilities led to intermittent misalignment of the spray-cone axis and occasional decoupling of the nozzle from its fixed position. To address these limitations, we embarked on a process of iterative redesign. Structural reinforcements were added to the mounting frame and locking mechanisms were refined to restrict unwanted translational motion of the assembly. Additionally, vibration-damping materials were incorporated at the motor-mount interface, and the wiring configuration was simplified to streamline intraoperative handling.
Successive generations of the prototype were evaluated under the same benchtop and ex vivo conditions, with real-time monitoring of spray-cone geometry, rotational trajectory, and mechanical robustness. Design modifications continued until the prototype demonstrated consistent, smooth, conical pendulum motion of the nozzle in all tested orientations while maintaining positional fixation equivalent to that of conventional laparoscopic instruments.
Development of a universal medical clamp. Upon confirmation of adequate performance in the reinforced prototype, focus shifted to developing a universal, electrically powered medical clamp suitable for integration into various laparoscopic access ports. The clamp was designed to provide secure attachment of the nozzle and rotational assembly, ensuring operator safety and device compatibility with standard trocars and cannulas. The clamp’s configuration permitted rapid deployment and removal in surgical settings, and its modularity enabled adaptability for future iterations of the RIPAC system or other laparoscopic aerosolization applications.
Results
Proof-of-concept mockup device. We first developed a universal motorized medical clamp as a mockup to enable stable conical pendulum motion for RIPAC. This device consisted of a support structure equipped with three simple fixed joints, each providing one degree of freedom (Figure 1), in combination with a motor unit designed to induce conical pendulum motion. As shown in Figure 2, we constructed a clamp compatible with use of the rotational motor and attached the nozzle at an oblique angle, thereby directing the system to facilitate the required conical pendulum movement. After confirming satisfactory operation in dry-lab settings, we proceeded to preclinical testing using a porcine model, as illustrated in Figure 3.
Proof-of-concept mockup device for rotational intraperitoneal pressurized aerosol chemotherapy.
Nozzle inserted obliquely via the clamp connected to the rotational motor.
Preclinical testing of a universal motorized medical clamp with three simple fixed joints to withstand the weight through multiple procedures. *Site of conical pendulum motion.
During these in vivo experiments, we observed that the nozzle’s conical pendulum motion repeatedly ceased when applied to the distended abdominal wall of the pig due to shifts in the center of gravity. Moreover, the three simple fixed joints used to secure the rotational motor failed to withstand the instrument’s weight through multiple RIPAC procedures, resulting in structural collapse of the support during repeated use.
Simple joint reinforcement mock-up device. To address the limitations of the initial mockup model, we enhanced the design by introducing a device capable of maintaining degrees of freedom while providing stable rotational motion. In particular, the motorized rotational assembly was prone to repeated interruptions in conical pendulum motion due to continuous shifts in the center of gravity, highlighting the necessity for a solution that would be alone to direct the nozzle spray into two or more directions (Figure 4).
Diagram of the nozzle used in this study that sprays liquid as an aerosol in two linear directions.
Furthermore, to allow movements with three or more degrees of freedom, we improved upon the simple fixed-joint configuration. To overcome the primary limitation of the initial model - namely, instability of the joint under motor load - we reconfigured the support structure such that the joints connecting the motor to its support simultaneously enabled motion along the X, Y, and Z axes. This integrated joint system provided enhanced structural robustness and flexibility. In addition, the motor responsible for nozzle rotation was re-engineered to optimize compatibility with the improved universal electric medical clamp (Figure 5).
Simple mock-up of a device for joint reinforcement. ① Nozzle pipe; ② O-ring; ③ O-ring; ④ coupler; ⑤ fitting; ⑥ pipe nut; ⑦ motor; ⑧ luer lock; ⑨ rotary fitting; ⑩ coupler; ⑪ nozzle.
Hydraulic joint reinforcement device. However, in the case of simple joint reinforcement mock-up devices, although the degree of freedom increased, it caused clinically uncomfortable situations due to the need to set each joint multiple times. To address this, the device was converted to one with a hydraulic joint section, which simplified the joints, increased fixation strength, and allowed for a greater degree of freedom.
The final device was developed as shown in Figure 6, featuring a single hydraulic joint and a universal electric medical clamp with a simple fixed joint having one degree of freedom for enhanced motor fixation. Specifically, the hydraulic joint was first installed to insert the nozzle vertically into the various curves and ridges of the abdominal wall, and the device was designed to enable fine adjustment of the nozzle position through the single-degree-of-freedom joint. The rotation motor was applied with slight modifications to the design developed in the previous stage.
Hydraulic joint-reinforcement device.
Discussion
The primary aim of this study was to develop a universal electric medical clamp capable of enabling stable conical pendulum-type aerosolization of chemotherapeutic agents during RIPAC procedures. Initially, our efforts focused on engineering a clamp mechanism that would facilitate the required conical pendulum motion. However, we encountered notable limitations in the clinical feasibility of the early prototypes. Specifically, the restricted degrees of freedom inherent to conventional medical device systems, frequent interruptions in nozzle rotation due to shifts in the center of gravity during pendular motion, and the substantial weight of the motor all contributed to difficulties in maintaining a fixed and stable nozzle position throughout the procedure. These shortcomings demonstrated that the initial designs were not clinically applicable.
In the second iteration, we reinforced the clamp structure to address the issue of nozzle fixation under motor load. While this approach offered enhanced stability, it resulted in an excessive number of locking components that needed to be manipulated to achieve the desired positioning. This complexity significantly diminished the clinical usability of the device, particularly because RIPAC must be performed in the sterile field of the operating room. Frequent and complex adjustments not only prolong the procedure but also increase the risk of accidental device detachment, which can compromise the sterile environment and introduce the potential for contamination.
To address these challenges, the final prototype incorporated a hydraulic joint mechanism in place of purely mechanical locking components. The hydraulic solution provided strong holding force with smooth, finely controlled adjustments, thereby accommodating the motor’s weight while maintaining precise nozzle positioning. Although it was not possible to fully resolve the issue of displacement of the center of gravity during conical pendulum motion – a limitation that prompted consideration of an alternative oblique nozzle design – the development of a universal, motorized medical clamp capable of stable nozzle rotation nonetheless represents a significant advance in the prototyping of RIPAC technology. This work lays a foundation for future improvements and clinical translation of rotational intraperitoneal aerosol chemotherapy devices.
However, recent efforts have focused on improving spray performance by modifying the nozzle itself to enhance the spray angle. Approaches such as varying the direction of the spray and incorporating additional devices at the nozzle tip have been developed, with some designs achieving spray angles of up to 150° (14, 15). While these modifications offer the advantage of a wider spray angle, they do not effectively resolve the issue of drug accumulation primarily along the central axis of the spray. In contrast, RIPAC enables more uniform drug distribution by dynamically altering the orientation of the spray center through rotational movement. This strategy has the potential to further increase intraperitoneal drug concentrations and enhance tissue penetration by maximizing the drug amount delivered per unit surface area of the peritoneum (11). Such improvements are supported by recent studies and indicate a promising direction for optimizing intraperitoneal chemotherapy delivery (16).
Through this study, we were able to develop a prototype of a universal electric medical clamp that can implement RIPAC. We expect that the clinical introduction of the RIPAC platform, which can resolve the problem of uneven drug delivery (a disadvantage of PIPAC), increase drug concentration on the peritoneal surface, overcome the limitations of multidrug resistance, and thereby maximize treatment response, will be possible in the near future.
Acknowledgements
The Authors sincerely appreciate Dreampac Corporation (Wonju, Republic of Korea) and Precision Medicine for Peritoneal Metastasis Corporative (Wonju, Republic of Korea) for providing the materials and related costs necessary for developing RIPAC in this study.
Footnotes
Authors’ Contributions
Conceptualization: K.H.H., S.L. and H.S.K. Data collection and curation: K.H.H., S.L. and H.S.K. Formal analysis: S.L. and H.S.K. Funding acquisition: H.S.K. Investigation: H.S.K. Methodology: H.S.K. Writing – original draft: K.H.H. and S.L. and H.S.K. Writing – review and editing: All Authors. All Authors have read and agreed to the published version of the manuscript.
Conflicts of Interest
Hee Seung Kim is the Chief Executive Officer of Dreama Corporation (Wonju, Republic of Korea). Senge Lee is the Chief Executive Officer and a director of Precision Medicine for Peritoneal Metastasis Corporative (Wonju, Republic of Korea). Kyung Hee Han declares no conflict of interest.
Funding
This work was supported by Commercializations Promotion Agency for R&D Outcomes grant funded by the Korea government (the Ministry of Science and ICT; No. 2710019525), Korea Technology and Information Promotion Agency for SMEs (TIPA; No. 2420005382), Korea Institute of Startup & Entrepreneurship Development (KISED, No. 20264235), Seoul National University Hospital (No. 0320232140; 0420222060; 0320212060), and Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (RS-2025-25400201).
Artificial Intelligence (AI) Disclosure
No artificial intelligence (AI) tools, including large language models or machine-learning software, were used in the preparation, analysis, or presentation of this manuscript.
- Received August 17, 2025.
- Revision received November 2, 2025.
- Accepted November 6, 2025.
- Copyright © 2026 The Author(s). Published by the International Institute of Anticancer Research.
This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).
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