Recent advances in polymeric drug delivery systems

Yong Kiel Sung,Sung Wan Kim 한국생체재료학회 2020 생체재료학회지 Vol.24 No.2

Background: Polymeric drug delivery systems have been achieved great development in the last two decades. Polymeric drug delivery has defined as a formulation or a device that enables the introduction of a therapeutic substance into the body. Biodegradable and bio-reducible polymers make the magic possible choice for lot of new drug delivery systems. The future prospects of the research for practical applications has required for the development in the field. Main body: Natural polymers such as arginine, chitosan, dextrin, polysaccharides, poly (glycolic acid), poly (lactic acid), and hyaluronic acid have been treated for polymeric drug delivery systems. Synthetic polymers such as poly (2-hydroxyethyl methacrylate), poly(N-isopropyl acrylamide)s, poly(ethylenimine)s, dendritic polymers, biodegradable and bio-absorbable polymers have been also discussed for polymeric drug delivery. Targeting polymeric drug delivery, biomimetic and bio-related polymeric systems, and drug-free macromolecular therapeutics have also treated for polymeric drug delivery. In polymeric gene delivery systems, virial vectors and non-virial vectors for gene delivery have briefly analyzed. The systems of non-virial vectors for gene delivery are polyethylenimine derivatives, polyethylenimine copolymers, and polyethylenimine conjugated bio-reducible polymers, and the systems of virial vectors are DNA conjugates and RNA conjugates for gene delivery. Conclusion: The development of polymeric drug delivery systems that have based on natural and synthetic polymers are rapidly emerging to pharmaceutical fields. The fruitful progresses have made in the application of biocompatible and bio-related copolymers and dendrimers to cancer treatment, including their use as delivery systems for potent anticancer drugs. Combining perspectives from the synthetic and biological fields will provide a new paradigm for the design of polymeric drug and gene delivery systems.

Drug delivery to the brain via the nasal route of administration: exploration of key targets and major consideration factors

정승현,장지훈,이용복 한국약제학회 2023 Journal of Pharmaceutical Investigation Vol.53 No.1

Background Cranial nerve-related diseases such as brain tumors, Alzheimer’s disease, and epilepsy are serious diseases that continue to threaten human. Brain-related diseases are increasing worldwide, including in the United States and Korea, and these increases are closely related to the exposure to harmful substances and excessive stress caused by rapid industrialization and environmental pollution. Drug delivery to the brain is very important for the effective prevention and treatment of brainrelated diseases. However, due to the presence of the blood–brain barrier and the extensive first-pass metabolism effect, the general routes of administration such as oral and intravenous routes have limitations in drug delivery to the brain. Therefore, as an alternative, the nasal-brain drug delivery route is attracting attention as a route for effective drug delivery to the brain. Areas covered This review includes physiological factors, advantages, limitations, current application status, especially in clinical applications, and the necessary factors for consideration in formulation development related to nasal-brain drug delivery. Expert opinion The nasal-brain drug delivery route has the advantage of enhancing drug delivery to the brain locally, mainly through the olfactory route rather than the systemic circulation. The nasal-brain lymphatic system has recently attracted attention, and it has been implied that the delivery of anticancer drugs to the brain nervous system is possible effectively. However, there are limitations such as low drug permeability, as well as nasal mucosa and the mucociliary system, as obstacles in nasal-brain drug delivery. Therefore, to overcome the limitations of nasal-brain drug delivery, the use of nanocarriers and mucoadhesive agents is being attempted. However, very few drugs have been officially approved for clinical application via the nasal-brain drug delivery route. This is probably because the understanding of and related studies on nasal-brain drug delivery are limited. In this review, we tried to explore the major considerations and target factors in drug delivery through the nasal-brain route based on physiological knowledge and formulation research information. This will help to provide a mechanistic understanding of drug delivery through the nasal-brain route and bring us one step closer to developing effective formulations and drugs in consideration of the key factors for nasal-brain drug delivery.

Construction of Programmable Drug Delivery System with Additive Manufacturing

명노현(Noehyun Myung),강현욱(Hyun-Wook Kang) Korean Society for Precision Engineering 2018 한국정밀공학회지 Vol.35 No.9

A programmable drug delivery system can control the release rate of a drug. It can minimize side effects while maximizing therapeutic effects. In this research, we investigated the feasibility of producing a programmable drug delivery system using 3D printing technology. A capsule with a micro-orifice and a drug-laden hydrogel was designed. The designed system was then fabricated by the printing process using polycaprolactone and hydrogel. The printed drug delivery system was immersed in PBS at 37°C and the number of molecules released was measured thorough colorimetric analysis. The effect of diameter and length of the micro-orifice and concentration of the hydrogel on drug release characteristics was then determined. The initial burst release rate was found to be increased with increasing orifice size. Increasing the length of the orifice linearly delayed the start time of drug release. At length of 600 μm and 1,200 μm, drug release was initiated after 36 h and 72 h for, respectively. When the concentration of hydrogel was increased, drug release rate tended to decrease. These results successfully confirmed that a drug delivery system with controlled release rate and initiation time could be manufactured using 3D printing technology.

Designing a drug delivery system for improved tumor treatment and targeting by functionalization of a cell-penetrating peptide

Shafq Al‑azzawi,Dhafir Masheta 한국약제학회 2019 Journal of Pharmaceutical Investigation Vol.49 No.6

Antitumor drugs activity is often limited due to the lack of satisfactory tumor specificity and bioavailability. Therefore, it is essential to conjugate the antitumor drug to a specific delivery system that can discriminate between tumors and normal tissue, and potentiate the activity. Purpose: the study was aimed to design a delivery system employing a cell-penetrating peptide, TAT, functionalized with a tumor targeting peptide, CREKA, and loaded with antitumor drug via a biodegradable linkage. Methods: the delivery system was synthesized using solid phase peptide synthesis and characterized by mass spectra and HPLC technique. Confocal microscopy and flow cytometry were used to examine the cellular uptake of the drug conjugate by malignant and normal cells whereas cell viability was tested to assess its cytotoxicity. Inhibition assay on dihydrofolate reductase (DHFR) to study the drug conjugate efficacy, and its stability examination were also performed. Results: characterization results confirmed successful synthesis of the delivery system and its conjugation with the drug. In addition, cellular translocation studies revealed higher cellular uptake of drug conjugate by malignant cell. The results also showed a better efficacy of the drug in conjugation in cytotoxicity and in the inhibition of DHFR and more stability at neutral pH medium. Conclusion: the functionalization with CREKA targeted the delivery of the antitumor drug to the malignant breast cells, decreasing its distribution to the normal cells. Hence this study demonstrated the potential of the designed delivery system to be used in delivering and translocating of therapeutic agents into a specific tumor tissue.

Innovative polymeric system (IPS) for solvent-free lipophilic drug transdermal delivery via dissolving microneedles

Dangol, M.,Yang, H.,Li, C.G.,Lahiji, S.F.,Kim, S.,Ma, Y.,Jung, H. Elsevier Science Publishers 2016 Journal of controlled release Vol.223 No.-

<P>Lipophilic drugs are potential drug candidates during drug development. However, due to the need for hazardous organic solvents for their solubilization, these drugs often fail to reach the pharmaceutical market, and in doing so highlight the importance of solvent free systems. Although transdermal drug delivery systems (TDDSs) are considered prospective safe drug delivery routes, a system involving lipophilic drugs in solvent free or powder form has not yet been described. Here, we report, for the first time, a novel approach for the delivery of every kind of lipophilic drug in powder form based on an innovative polymeric system (IPS). The phase transition of powder form of lipophilic drugs due to interior chemical bonds between drugs and biodegradable polymers and formation of nano-sized colloidal structures allowed the fabrication of dissolving microneedles (DMNs) to generate a powerful TDDS. We showed that IPS based DMN with powder capsaicin enhances the therapeutic effect for treatment of the rheumatic arthritis in a DBA/1 mouse model compared to a solvent-based system, indicating the promising potential of this new solvent-free platform for lipophilic drug delivery. (C) 2016 Elsevier B.V. All rights reserved.</P>

Recent approaches to investigate drug delivery systems through the lymphatic pathway using oral lipid-based formulations

Jeong So-Jeong,Song Woo Yul,박천웅,김동욱 한국약제학회 2024 Journal of Pharmaceutical Investigation Vol.54 No.2

Background Lymphatic oral drug delivery systems are considered optimal for enhancing oral drug delivery. They offer the advantage of delivering drugs directly to the immune system while bypassing first-pass metabolism. Consequently, they are actively researched in the field of pharmaceuticals. Novel drug delivery systems are employed to administer drugs through the lymphatic system via the oral route. Area covered This review delves into the current understanding of drug delivery systems through the lymphatic pathway, with a focus on those utilizing long-chain triglycerides. We explore the mechanisms of delivery to the lymphatic pathway, characteristics of drugs used for this purpose, composition of lipid-based formulations, preparation methods, evaluation methods, and notable case studies. Expert opinion With the discovery of more lipophilic drug candidates, there is a growing interest in designing formulations to maximize lymphatic transport. Stimulating intestinal lymphatic transport holds the potential for benefits such as reducing first-pass metabolism and delivering high drug concentrations to the lymphatic system. To enhance the utility of intestinal lymph as an alternative means of transport to the systemic circulation, further research is essential. This research should address the underlying mechanisms of drug binding to lipoproteins in intestinal cells, as well as the effects of lipids and formulation excipients on this process.

일반연구논문 ; 마약수사에서의 통제배달기법 고찰 - 마약류관리에관한법률위반사범 중 밀수범죄와 관련하여 -

예상균 ( Sang Kyun Ye ) 한국법정책학회 2015 법과 정책연구 Vol.15 No.2

우리나라는 마약 청정국으로 분류되고 있다. 그 만큼 국가에서 강력한 의지를 가지고 마약 통제정책을 실시하고 있다는 의미이다. 강력한 마약 통제정책은 국내에서의 마약유통을 근절하는 것뿐만 아니라 국외로부터의 마약반입을 원천적으로 봉쇄하겠다는 의미도 포함한다. 마약의 국내제조가 사실상 사라진 현시점에서 마약통제 정책을 효과적으로 달성하려면 해외로부터의 마약반입 차단이 무엇보다도 중요하다. 결국 공항 및 항만 등에서 엄격한 감시체계를 구축하여 여행객 내지 수화물에 대한 철저한 감시의 필요성이 높아졌다고 할 수 있다. 그러나 현재 출입국 및 통관절차는 서비스적 측면이 부각되어 간편한 출입국 심사, 신속한 통관절차를 지향하고 있는 실정이므로 수화물 등에 대한 철저한 감시는 매우 어려운 일이다. 그렇다면 최첨단 기술을 이용한 간편하고 신속한 검사 및 정보 축적을 통한 마약 혐의자에 국한된 조사만이 현재의 서비스 정신에 충실한 사정이다. 마약밀수 사건에서는 통제배달 수사기법이 종종 사용되고 있다. 사람이 직접 마약을 운반하는 경우보다는 국제우편 및 소포를 통하여 한국으로 마약이 반입되는 것이 더 빈번히 발생하는 일이기 때문이다. 마약이 들어있는 우편물의 이동경로를 따라 실제 반입자를 추적하여야만 이를 수입하고자 했던 범인들을 검거할 수 있다. 최근에는 통제배달의 前단계에서 세관직원이 압수·수색영장 없이 국제우편물을 개봉한 후 시료를 채취한 행위가 적법한지, 수사기관이 압수·수색영장 없이 통제배달 수사기법을 활용한 것이 불법이 아닌지에 대한 유의미한 대법원 판결이 선고되었다. 통제배달 수사기법과 관련된 일련의 과정에 영장주의를 관철하려는 주장들은 세관에서의 해당 우편물의 검사과정 자체를 강제수사인 압수·수색으로 보거나 수사기관이 마약을 확보한 사실 자체를 강제수사인 압수로 보아 이에 대한 영장을 발부받지 아니한 채 배달한 것 자체가 위법하다는 견해를 제시하고 있는 것으로 보인다. 그러나 세관 통관절차에서의 검사는 수사개시 이전단계로서 이에 대하여 형사 소송법적 잣대를 일률적으로 적용하기에는 어려운 점이 있고, 통제배달 수사기 법은 용어 자체적으로도 수사기관의 압수를 전제로 하지 않을 뿐만 아니라 ‘마약류의 분산을 방지하기 위하여 충분한 감시체제가 확보되어 있는 마약류범죄의 수사’기법이기 때문에 배달과정에서의 수사기관의 마약확보를 강제수사인 압수로 보기에는 어렵다. South Korea is classified as a drug-free country. It means that South Korea government carries out the powerful drug control policy with strong will. Powerful drug control policy means it will fundamentally block the importation of drugs from abroad as well as it will eradicate drug trafficking in the country. In order to achieve the drug control policies efficiently, It is most important to block the import of drugs from abroad at the present time domestic production of drug is disappeared. Eventually, it increases the need to establish a strict monitoring system in the airport and port can be a need for thorough monitoring of the traveler and luggage. But, now immigration and customs clearance procedures are highlighted by this easy and speedy service aspect, so it is very difficult to make a perfect surveillance for the traveler and luggage. Then, the speedy surveillance by using high-tech and the limited investigation on the drug suspect by acuumulating information are the only way which agree with the present service mind. Controlled delivery is often used in the case of drug smuggling, because the drug import case by international mail or package more often happens than the direct personal delivery case. The only way to arrest the real importer is to trace the true receiver along the path of movement of the mail containing the drug. Recently, the supreme court ruling was sentenced whether it is legal or not that customs agent open the international package without search and seizure warrant at the previous step of controlled delivery and whether it is illegal or not that investigator do controlled delivery without search and seizure warrant. The arguments which attain its goals of warrant ideology at the controlled delivery procedure consider the screening of the mail by Customs and the possession of drug by investigator as compulsory investigation like search and seizure. So they assert that the controlled delivery without warrant is illegal. But, Criminal procedure yardstick is diffiult to be applied in all cases in point that the inspection at the customs clearence process is prior to the beginning of an investigation. Controlled delivery, the term of itself is not based upon a premise of investigator`s seizure. And because Controlled delivery is drug crime investigation techniques equipped with sufficient monitoring system in order to prevent the spread of drug, it is not seizure as compulsory investigation that the investigator has a possession of drug.

FA/Mel@ZnO nanoparticles as drug self-delivery systems for RPE protection against oxidative stress

Yi, Caixia,Yu, Zhihai,Sun, Xin,Zheng, Xi,Yang, Shuangya,Liu, Hengchuan,Song, Yi,Huang, Xiao Techno-Press 2022 Advances in nano research Vol.13 No.1

Drug self-delivery systems can easily realize combination drug therapy and avoid carrier-induced toxicity and immunogenicity because they do not need non-therapeutic carrier materials. So, designing appropriate drug self-delivery systems for specific diseases can settle most of the problems existing in traditional drug delivery systems. Retinal pigment epithelium is very important for the homeostasis of retina. However, it is vulnerable to oxidative damage and difficult to repair. Worse still, the antioxidants can hardly reach the retina by non-invasive administration routes due to the ocular barriers. Herein, the targeted group (folic acid) and antioxidant (melatonin) have been grafted on the surface of ZnO quantum dots to fabricate a new kind of drug self-delivery systems as a protectant via eyedrops. In this study, the negative nanoparticles with size ranging in 4~6 nm were successfully synthesized. They could easily and precisely deliver drugs to retinal pigment epithelium via eyedrops. And they realized acid degradation to controlled release of melatonin and zinc in retinal pigment epithelium cells. Consequently, the structure of retinal pigment epithelium cells were stabilized according to the expression of ZO-1 and β-catenin. Moreover, the antioxidant capacity of retinal pigment epithelium were enhanced both in health mice and photic injury mice. Therefore, such new drug self-delivery systems have great potential both in prevention and treatment of oxidative damage induced retinal diseases.

약물전달과 재생의학 기술

이해방 ( Hai Bang Lee ),정제교 ( Je Kyo Jeong ),손세일 ( Se Il Sohn ),변영로 ( Young Ro Byun ),기민효 ( Min Hyo Ki ),서중기 ( Jung Ki Seo ) 한국조직공학과 재생의학회 2009 조직공학과 재생의학 Vol.6 No.4

Drug delivery system(DDS) has been extensively applied the various areas as (1) novel methods for drug administration through several route, (2) development of novel polymeric carrier, and (3) tissue engineering and regenerative medicine. The aim of this review is to report the recent progress of "Development of controlled drug delivery system" supported by Korean Intellectual and Economy(KOIE) for 2004~2009. This project is composed by 5 subproject as (1) development of novel osmotic pump, (2) development of liposome delivery system, (3) development of DDS by bile acid transporter, (4) protein drug delivery system using thermo-sensitive hydrogel, and (5) development of novel transdermal drug delivery system. DDS system might be the core and platform technology for the application of diagnosis, bioinstrument, tissue engineering, regenerative medicine and pharmaceutical industries.

In vivo and in vitro testing of the efficacy of a novel drug delivery fabric

( Ji Yeon Hong ),( Won Jong Oh ),( Tae Rin Kwon ),( I Song Im ),( Sun Young Choi ),( Beom Joon Kim ),( Chang Kwun Hong ) 대한피부과학회 2015 대한피부과학회 학술발표대회집 Vol.67 No.2

Background: Transdermal drug delivery systems provide more reliable and consistent administration than oral routes because they avoid the effects of digestive degradation and first-pass liver metabolism. However, penetration of any compound through the skin is prevented primarily by the epidermis. Objectives: We assess the efficacy of a novel fabric for drug delivery, with the aim of developing an improved method for transdermal drug delivery. Methods: Guinea pigs were divided into a control group and three test groups; treated with slimming cream and no fabric, 100% cotton fabric, or our novel fabric. The amount of fat loss was evaluated by histological staining. The skin penetrance of rhodamine B base was assessed using a fluorescence penetration test and the transdermal penetration of caffeine was also evaluated in vitro using Franz diffusion cells each. Results: Drug delivery with our novel fabric resulted in reduction in adipocyte size after 28 days. The fabric also enhanced the transdermal delivery of rhodamine B base and caffeine penetration compared with the control groups. Conclusion: Our novel drug delivery fabric is an effective way to enhance the transdermal delivery of slimming cream. This fabric can potentially be used to enhance the transdermal delivery of several agents, including drugs.