Drug Delivery System For Treatment Research Articles

Formulation and Evaluation of Ethosomal Cream containing Resveratrol for the Treatment of Contact Dermatitis

Objective: The aim of this study was to formulate and evaluate ethosomal cream containing resveratrol for the treatment of contact dermatitis. Method: Resveratrol-loaded ethosome was prepared using cold method. The prepared ethosomes were assessed for entrapment efficiency (%), TEM analysis and sedimentation rate to determine the optimal formulation for loading into cream base. The selected formulation was further investigated for particle size distribution and zeta potential. A cream base was formulated using fusion and trituration method and selected for loading with the ethosomal suspension, meeting specification suitable for topical delivery. Ethosomal cream formulations were evaluated for drug content, ex -vitro diffusion by using goat skin, skin retention, microbiological study and stability study. Result and Discussion: The formulation E3 was selected for loading in the optimized cream base (F4) to obtain a topical cream containing ethosomes of resveratrol. The release study reveals that release was controlled for the 24 hours. The drug release in buffer was less than 17% from all the formulations after 24 hours. The drug content of resveratrol in goat skin and cream remained in donor compartment indicates that the drug retention in skin was high in all the formulations, which is desirable for the topical formulations. The best possible release kinetics of the formulation loaded with resveratrol containing ethosomes was found to be zero order. The ‘n’ value from Peppas’s model indicated that the drug release was by Fickian diffusion. Stability study indicates that all the cream formulations were stable after a time period of one month. Conclusion: The present study conclusively supported that ethosomal cream containing resveratrol to be an advantageous topical drug delivery system in treatment of ACD. However detail in- vivo study should be conducted in future to be justify the in- vitro study. Keywords: Resveratrol, Ethosome, Cream, Contact dermatitis.

The Emerging Roles of Nanocarrier Drug Delivery System in Treatment of Intervertebral Disc Degeneration-Current Knowledge, Hot Spots, Challenges and Future Perspectives.

Low back pain (LBP) is a common condition that has substantial consequences on individuals and society, both socially and economically. The primary contributor to LBP is often identified as intervertebral disc degeneration (IVDD), which worsens and leads to significant spinal problems. The conventional treatment approach for IVDD involves physiotherapy, drug therapy for pain management, and, in severe cases, surgery. However, none of these treatments address the underlying cause of the condition, meaning that they cannot fundamentally reverse IVDD or restore the mechanical function of the spine. Nanotechnology and regenerative medicine have made significant advancements in the field of healthcare, particularly in the area of nanodrug delivery systems (NDDSs). These approaches have demonstrated significant potential in enhancing the efficacy of IVDD treatments by providing benefits such as high biocompatibility, biodegradability, precise drug delivery to targeted areas, prolonged drug release, and improved therapeutic results. The advancements in different NDDSs designed for delivering various genes, cells, proteins and therapeutic drugs have opened up new opportunities for effectively addressing IVDD. This comprehensive review provides a consolidated overview of the recent advancements in the use of NDDSs for the treatment of IVDD. It emphasizes the potential of these systems in overcoming the challenges associated with this condition. Meanwhile, the insights and ideas presented in this review aim to contribute to the advancement of precise IVDD treatment using NDDSs.

Evaluation of Different Local Drug Delivery Systems in Treatment of Periodontitis: An Institutional Study

Periodontal disease can be treated in both non-surgical and surgical therapy. There could be a possible reason why non-surgical therapy causes failure due to bacteria virulent factors and also the depth of periodontal pocket is greater than the instrumentation available, drug concentration is low in GCF as well as in saliva. To overcome this problem a treatment protocol that would include short-term usage of systemic and or local antimicrobial agents is being tried as an adjunct to mechanical therapy in treatment of periodontal diseases. A total of 540 sites, from 72 patients in different quadrants of the mouth received these treatment modalities in assigned quadrants such as scaling and root planning using both hand and ultrasonic instruments under local anesthesia (if required), combination therapy and local drug delivery alone. Patients with periodontal diseased sites were divided into five groups, based on the local drug delivery system, as Group I: Elyzol (25% Metronidazole), Group II: Dentomycin (2% Minocycline hydrochloride), Group III: Metrogene (5% Metronidazole), Group IV: Periochip (2.5mg of Chlorhexidine gluconate) and Group V: Atridox (10% Doxycycline hyclate). In the present study, the bleeding index score showed better reduction, for all LDD systems. The results showed that SRP alone, and LDD alone had shown no significance in overall reduction of pocket depth where clinical parameters (Plaque Index, Gingival Bleeding Index and Gingival Index). Although the combined treatment of scaling and root planing plus the local drug therapy reported to have a significant benefit over SRP alone in the treatment of periodontal lesions. Keywords: Anti-Bacterial Agents, Metronidazole, Minocycline, Doxycycline, Chlorhexidine, Local Drug Delivery Systems, Humans, Periodontitis, Periodontal Pocket, Root Planing

Tetramethylpyrazine-loaded liposomes surrounded by hydrogel based on sodium alginate and chitosan as a multifunctional drug delivery System for treatment of atopic dermatitis

Tetramethylpyrazine (TMP) has low bioavailability due to its fast metabolism and short half-life, which is not conducive to transdermal treatment of atopic dermatitis (AD). Therefore, in this study, TMP was encapsulated into liposomes (Lip) by film dispersion method, and then the surface of Lip was modified by sodium alginate (ALG) and chitosan (CS). The tetramethylpyrazine-loaded liposomes in sodium alginate chitosan hydrogel called T-Lip-AC hydrogel. In vitro experiments, we found that T-Lip-AC hydrogel not only had the antibacterial effect of CS, but also enhanced the anti-inflammatory and antioxidant effects of TMP. In addition, T-Lip-AC hydrogel could also provide a moist healing environment for AD dry skin and produce better skin permeability, and can also achieve sustained drug release, which is conducive to the treatment of AD. The lesions induced by 1-chloro-2,4-dinitrobenzene were used as the AD lesions model to test the therapeutic effect of the T-Lip-AC hydrogel on AD in vivo. The studies have showed that T-Lip-AC hydrogel could effectively promote wound healing. Therefore, we have developed a T-Lip-AC hydrogel as multifunctional hydrogel drug delivery system, which could become an effective, safe and novel alternative treatment method for treating AD.

Polymer-Based Self-Assembled Drug Delivery Systems for Glaucoma Treatment: Design Strategies and Recent Advances.

Glaucoma has become the world's leading cause of irreversible blindness, and one of its main characteristics is high intraocular pressure. Currently, the non-surgical drug treatment scheme to reduce intraocular pressure is a priority method for glaucoma treatment. However, the complex and special structure of the eye poses significant challenges to the treatment effect and safety adherence of this drug treatment approach. To address these challenges, the application of polymer-based self-assembled drug delivery systems in glaucoma treatment has emerged. This review focuses on the utilization of polymer-based self-assembled structures or materials as important functional and intelligent carriers for drug delivery in glaucoma treatment. Various drug delivery systems, such as eye drops, hydrogels, and contact lenses, are discussed. Additionally, the review primarily summarizes the design strategies and methods used to enhance the treatment effect and safety compliance of these polymer-based drug delivery systems. Finally, the discussion delves into the new challenges and prospects of employing polymer-based self-assembled drug delivery systems for the treatment of glaucoma.

Nanotechnology-based drug delivery systems for treatment of knee injuries and Alzheimer’s disease – a review

The effective treatment of human illnesses relies on the ability to deliver therapeutic compounds to diseased sites in a highly efficient manner. However, conventional therapeutic strategies often require high systemic administration due to non-specific biodistribution and rapid metabolism of free drug molecules before they can reach their intended targets which leads to undesirable side effects. Nanotechnology offers a solution to mitigate these issues by allowing the development of drug delivery systems (DDS) within the nanometer size range, which can alter the pharmacological and therapeutic effects of drug molecules. These novel DDS have several advantages over traditional large-scale systems, including altered pharmacokinetic behavior and improved payload, owing to their small size. Moreover, their surface chemistry can be easily modified to attach targeting and therapeutic molecules for specific curative and therapeutic applications. In this comprehensive review, we explore and present the potential of nanoparticles as a highly effective drug delivery system for the treatment of knee injuries and Alzheimer’s disease. With the aim of addressing the challenges that are associated with drug delivery, nanotechnology has emerged as an increasingly important area of research. Scientists have conducted extensive investigations into nanosystems with varying compositions and biological properties for use in drug delivery applications. In order to ensure efficient drug delivery, it is critical to understand how nanomaterials interact with the biological environment, target cell-surface receptors, release drugs, administer multiple drugs, and maintain the stability of therapeutic agents. The recognition and appreciation of the molecular mechanisms that are involved in cell signaling in relation to the disease under investigation is of fundamental importance.

A comprehensive and updated review on the applications of vesicular drug delivery systems in treatment of brain disorders: A shelter against storms

A comprehensive and updated review on the applications of vesicular drug delivery systems in treatment of brain disorders: A shelter against storms

A disulfiram/copper gluconate co-loaded bi-layered long-term drug delivery system for intraperitoneal treatment of peritoneal carcinomatosis

To develop a long-term drug delivery system for the treatment of primary and metastatic peritoneal carcinoma (PC) by intraperitoneal (IP) injection, a disulfiram (DSF)/copper gluconate (Cu-Glu)-co-loaded bi-layered poly (lactic acid-coglycolic acid) (PLGA) microspheres (Ms) - thermosensitive hydrogel system (DSF-Ms-Cu-Glu-Gel) was established. Rate and mechanisms of drug release from DSF-Ms-Cu-Glu-Gel were explored. The anti-tumor effects of DSF-Ms-Cu-Glu-Gel by IP injection were evaluated using H22 xenograft tumor model mice. The accumulative release of DSF from Ms on the 10th day was 83.79% without burst release. When Ms were dispersed into B-Gel, burst release at 24 h decreased to 14.63%. The results showed that bis (diethyldithiocarbamate)-copper (Cu(DDC)2) was formed in DSF-Ms-Cu-Glu-Gel and slowly released from B-Gel. In a pharmacodynamic study, the mount of tumor nodes and ascitic fluid decreased in the DSF-Ms-Cu-Glu-Gel group. This was because: (1) DSF-Ms-Cu-Glu-Gel system co-loaded DSF and Cu-Glu, and physically isolated DSF and Cu-Glu before injection to protect DSF; (2) space and water were provided for the formation of Cu(DDC)2; (3) could provide an effective drug concentration in the abdominal cavity for a long time; (4) both DSF and Cu(DDC)2 were effective anti-tumor drugs, and the formation of Cu(DDC)2 occurred in the abdominal cavity, which further enhanced the anti-tumor activity. Thus, the DSF-Ms-Cu-Glu-Gel system can be potentially used for the IP treatment of PC in the future.

Recent advances in nanocarrier-based drug delivery systems in treatment of rheumatoid arthritis

Rheumatoid arthritis(RA) is a widely prevalent autoimmune inflammatory disease that severely affects patients' quality of life. Currently, conventional formulations against RA have several limitations, such as nonspecificity, poor efficacy, large drug dosages, frequent administration, and systemic side effects. Nanotechnology-based drug delivery systems have emerged as a promising stra-tegy for the diagnosis and treatment of RA since nanotechnology can overcome the limitations of traditional treatments and simplify the complexity of the disease. These systems enable targeted delivery of anti-inflammatory drugs to the inflamed areas through active and passive targeting, achieving specificity to the joints, overcoming the need for increased dosage and administration frequency, and reducing associated adverse reactions. This article aimed to review nanocarrier-based drug delivery systems in the field of RA and elucidate how nanosystems can be utilized to deliver therapeutic drugs to inflamed joints for controlling RA progression. By discussing the current issues and challenges faced by nanodrug delivery systems and highlighting the urgent need for solutions, this article offers theoretical support for further research on nanotechnology-based co-delivery systems in the future.

Panobinostat-loaded folate targeted liposomes as a promising drug delivery system for treatment of canine B-cell lymphoma.

Cancer is a major public health problem with over 19 million cases reported in 2020. Similarly to humans, dogs are also largely affected by cancer, with non-Hodgkin's lymphoma (NHL) among the most common cancers in both species. Comparative medicine has the potential to accelerate the development of new therapeutic options in oncology by leveraging commonalities between diseases affecting both humans and animals. Within this context, in the present study, we investigated the potential of panobinostat (Pan)-loaded folate-targeted PEGylated liposomes (FA-PEG-Pan-Lip) for the treatment of canine B-cell lymphoma, while contributing to new perspectives in comparative oncology. Two formulations were developed, namely: PEG-Pan-Lip and FA-PEG-Pan-Lip. Firstly, folate receptor expression in the CLBL-1 canine B-cell lymphoma cell line was assessed. After confirming receptor expression, both Pan-loaded formulations (PEG-Pan-Lip, FA-PEG-Pan-Lip) demonstrated dose-dependent inhibitory effects on CLBL-1 cell proliferation. The FA-PEG-Pan-Lip formulation (IC50 = 10.9 ± 0.03 nM) showed higher cytotoxicity than the non-targeted PEG-Pan-Lip formulation (IC50 = 12.9 ± 0.03 nM) and the free panobinostat (Pan) compound (IC50 = 18.32±0.03 nM). Moreover, mechanistically, both Pan-containing formulations induced acetylation of H3 histone and apoptosis. Flow cytometry and immunofluorescence analysis of intracellular uptake of rhodamine-labeled liposome formulations in CLBL-1 cells confirmed cellular internalization of PEG-Lip and FA-PEG-Lip formulations and higher uptake profile for the latter. Biodistribution studies of both radiolabeled formulations in CD1 and SCID mice revealed a rapid clearance from the major organs and a 1.6-fold enhancement of tumor uptake at 24 h for 111In-FA-PEG-Pan-Lip (2.2 ± 0.1 %ID/g of tumor) compared to 111In-PEG-Pan-Lip formulation (1.2±0.2 %ID/g of tumor). In summary, our results provide new data validating Pan-loaded folate liposomes as a promising targeted drug delivery system for the treatment of canine B-cell lymphoma and open innovative perspectives for comparative oncology.

TITLE: Modernized management and formulation of nanovesicular drug delivery systems for treatment of keratitis

TITLE: Modernized management and formulation of nanovesicular drug delivery systems for treatment of keratitis

Encapsulated Oxovanadium(IV) and Dioxovanadium(V) Complexes into Solid Lipid Nanoparticles Increase Cytotoxicity Against MDA-MB-231 Cell Line.

Solid lipid nanoparticles (SLN) have been considered lately as promising drug delivery system in treatment of many human diseases including cancers. We previously studied potential drug compounds that were effective inhibitors of PTP1B phosphatase - possible target for breast cancer treatment. Based on our studies, two complexes were selected for encapsulation into the SLNs, the compound 1 ([VO(dipic)(dmbipy)] · 2 H2O) and compound 2 ([VOO(dipic)](2-phepyH) · H2O). Here, we investigate the effect of encapsulation of those compounds on cell cytotoxicity against MDA-MB-231 breast cancer cell line. The study also included the stability evaluation of the obtained nanocarriers with incorporated active substances and characterization of their lipid matrix. Moreover, the cell cytotoxicity studies against the MDA-MB-231 breast cancer cell line in comparison and in combination with vincristine have been performed. Wound healing assay was carried out to observe cell migration rate. The properties of the SLNs such as particle size, zeta potential (ZP), and polydispersity index (PDI) were investigated. The morphology of SLNs was observed by scanning electron microscopy (SEM), while the crystallinity of the lipid particles was analyzed by differential scanning calorimetry (DSC) and X-ray diffraction (XRD). The cell cytotoxicity of complexes and their encapsulated forms was carried out against MDA-MB-231 breast cancer cell line using standard MTT protocols. The wound healing assay was performed using live imaging microscopy. SLNs with a mean size of 160 ± 25 nm, a ZP of -34.00 ± 0.5, and a polydispersity index of 30 ± 5% were obtained. Encapsulated forms of compounds showed significantly higher cytotoxicity also in co-incubation with vincristine. Moreover, our research shows that the best compound was complex 2 encapsulated into lipid nanoparticles. We observed that encapsulation of studied complexes into SLNs increases their cell cytotoxicity against MDA-MB-231 cell line and enhanced the effect of vincristine.

The Role of Gold Nanoparticles/Au-PEG-PAMAM as Drug Delivery System for Treatment of Breast Cancer

To enhance the cellular uptake and chemotherapeutic efficacy of a current chemotherapeutic medication, a nanoparticle drug carrier technology has been designed. Due to their distinctive electrical and optical characteristics, gold nanoparticles (Au NPs) have recently demonstrated intriguing medical and military uses. In the event that they come into touch with a biological system, little is known about their biocompatibility. Metallic nanoparticles have been successfully utilized for a kind of biological applications. A drug delivery system known as Au – PEG – PAMAM – DOX was produced by conjugating the dendrimer with the anti-cancer chemical doxorubicin (DOX) via an amide bond. The amount of DOX released from Au – PEG – PAMAM – DOX at a natural pH was negligible, but this amount significantly increased in an environment with a weak acidic milieu, according to studies on the release of medicines from acellular sources. A research into the intracellular release of the medication was carried out with the assistance of confocal laser scanning microscopy (CLSM). Recently conjugation to the nanosystem, in vitro viability experiments revealed an increase in the associated DOX cytotoxicity that could not be attributable to carrier components. This indicates that the effectiveness of the DOX was increased. In light of this, it has been hypothesized that the newly created pH-triggered multifunctional Au NPs- DOX nanoparticle system could pave the way for a viable platform for the intracellular delivery of a range of anticancer medicines. In the current study, the common Au NPs synthesis techniques and their well-established uses in diverse needs, particularly in biological sensing applications.

Regenerative marine waste towards CaCO3 nanoformulation for Alzheimer's therapy

Alzheimer's disorder (AD) is associated with behavioural and cognitive destruction with due respect to the neurological degeneration. Conventional therapeutic approach for treatment of AD using neuroprotective drugs suffered certain limitations such as poor solubility, insufficient bioavailability, adverse side effects at higher dose and ineffective permeability on blood brain barrier (BBB). Development of nanomaterial based drug delivery system helped to overcome these barriers. Hence the present work focused on encapsulating neuroprotective drug citronellyl acetate within CaCO3 nanoparticles to develop neuroprotective CaCO3 nanoformulation (CA@CaCO3 NFs). CaCO3 was derived from marine conch shell waste, while the neuroprotective drug citronellyl acetate was scrutinized by in-silico high throughput screening. In-vitro findings revealed that CA@CaCO3 nanoformulation exhibited enhanced free radical scavenging activity of 92% (IC50 value - 29.27 ± 2.6 μg/ml), AChE inhibition of 95% (IC50 value - 25.6292 ± 1.5 μg/ml) at its maximum dose (100 μg/ml). CA@CaCO3 NFs attenuated the aggregation of β-amyloid peptide (Aβ) and also disaggregated the preformed mature plaques the major risk factor for AD. Overall, the present study reveals that CaCO3 nanoformulations exhibits potent neuroprotective potential when compared to the CaCO3 nanoparticles alone and citronellyl acetate alone due to the sustained drug release and synergistic effect of CaCO3 nanoparticles and citronellyl acetate depicting the fact that CaCO3 can act as promising drug delivery system for treatment of neurodegenerative and CNS related disorders.

PIPAC nebulizer: How to test the new devices in the market, expert recommendations.

Pressurized intraperitoneal aerosol chemotherapy, named PIPAC, is now used in many centers around the world and as an intraperitoneal drug delivery system for treatment of peritoneal carcinomatosis. Recently, many of us have encountered problems during PIPAC procedures due to changes in material and production features of the original PIPAC nebulizer. Concomitantly, new PIPAC nebulizers proposed by other manufacturers are being launched on the market; which claim that they are the same as the original device in delivering PIPAC. However, these new devices are all different in terms of materials, technical characteristics and costs. We have considered that, to maintain the acquired results of PIPAC, we must ensure that the new systems are equivalent. The characteristics deemed essential by the expert group are as follows: 1: The nebulizer must be able to create droplets through an injector pressure between 10 and 20 bars, 2: The mean droplet size must be 3 micrometers, with 95% of the droplets between 0 and 10 micrometers, 3: The diffusion angle must be 70 degrees, which is the minimum.

Nanotechnology-Based Drug Delivery Systems in the Transdermal Treatment of Melanoma.

The incidence rate of melanoma is dramatically increasing worldwide, raising it to the fifth most common cancer in men and the sixth in women currently. Resistance generally occurs to the agents used in chemotherapy; besides their high toxicity destroys the normal cells. This study reviewed a detailed summary of the structure, advantages, and disadvantages of nanotechnology-based drug delivery systems in the treatment of melanoma, as well as some nanocarrier applications in animal models or clinical studies. Respective databases were searched for the target keywords and 93 articles were reviewed and discussed. A close study of the liposomes, niosomes, transferosomes, ethosomes, transethosomes, cubosomes, dendrimers, cyclodextrins, solid lipid nanoparticles, and carbon nanotubes (CNTs) was conducted. It was found that these nanocarriers could inhibit metastasis and migration of melanoma cells and decrease cell viability. Conclusively, some nanocarriers like liposomes, niosomes, and transferosomes have been discussed as superior to conventional therapies for melanoma treatment.

Abstract P046: CTLA4 targeted therapy using the lymphatic drug delivery system for treatment of metastatic lymph nodes

Abstract Background: Metastasis is the prime cause of cancer associated mortality. Lymph nodes (LNs) facilitate the systemic exposure of tumor cells, resulting in fatal systemic metastasis. Treatment of metastatic LNs is therefore imperative. However, successful treatment of metastatic LNs is challenging. Immune checkpoint inhibitor (ICI) therapy is an emerging therapy approved for several advanced malignancies. However, ICI therapy in the context of metastatic LNs remains unexplored due to the absence of reliable models and inquisition techniques. Additionally, while systemically delivered ICI therapy has delivered encouraging results, response is often erratic and mired by unwarranted side effects. To harness the benefits of ICI therapy, it is imperative to uncouple therapeutic response from off-target events. The present study sought to develop an effective intervention strategy using α-CTLA4 mAb for the treatment of metastatic LNs that addresses this unmet need. Methods: Using a murine model of LN metastasis, the therapeutic efficacy of low-dose α-CTLA4 mAb administered to different sites locally, using a novel lymphatic drug delivery system (LDDS) or intraperitoneally (i.p.) was examined. The mouse model was established using luciferase labelled cells in a recombinant inbred strain of mice exhibiting systemic lymphadenopathy (LM8-Luc cells; MXH10/Mo/lpr mice). Results: Therapeutic response was observed in mice treated by all strategies with α-CTLA4 mAb. However, response was erratic in mice administered α-CTLA4 mAb to tumor-free LN through LDDS or intraperitoneally. Strong and fairly consistent therapeutic response was observed upon local delivery of α-CTLA4 mAb through LDDS to tumor-harboring LN. Additionally, incidence of complete response, as indicated by the total-eradication of tumor by the pre-determined experimental endpoint was observed in 66.67% of mice treated by the administration of α-CTLA4 mAb to tumor-harboring LN as opposed to only 33.33% and 28.67% in mice treated by administration of α-CTLA4 mAb to the tumor-free LN or intraperitoneally. Furthermore, treatment using LDDS to tumor-bearing LN was also found to prevent metastases to liver and lung and significantly prolong survival. In stark contrast, treatment through LDDS to tumor-free LN or i.p., worsened survival as opposed to control group, likely due to the onset of immune related adverse events. In keeping with the same, body weight and spleen weights for the i.p. group, which had the worst survival amongst all the experimental groups, was found to drop. Conclusions: Administration strategy is a critical variable that affects ICI therapy associated anti-tumor response and toxicity in the context of metastatic LNs. Therapeutic response is potentiated upon delivery of α-CTLA4 mAb to tumor-harboring LN via LDDS. Citation Format: Radhika Mishra, Ariunbuyan Sukhbaatar, Shiro Mori, Tetsuya Kodama. CTLA4 targeted therapy using the lymphatic drug delivery system for treatment of metastatic lymph nodes. [abstract]. In: Proceedings of the AACR Special Conference: Precision Prevention, Early Detection, and Interception of Cancer; 2022 Nov 17-19; Austin, TX. Philadelphia (PA): AACR; Can Prev Res 2023;16(1 Suppl): Abstract nr P046.

Preparation of 6-Mercaptopurine Loaded Liposomal Formulation for Enhanced Cytotoxic Response in Cancer Cells.

6-Mercaptopurine (6-MP) is a well-known immunosuppressive medication with proven anti-proliferative activities. 6-MP possesses incomplete and highly variable oral absorption due to its poor water solubility, which might reduce its anti-cancer properties. To overcome these negative effects, we developed neutral and positively charged drug-loaded liposomal formulations utilizing the thin-film hydration technique. The prepared liposomal formulations were characterized for their size, polydispersity index (PDI), zeta potential, and entrapment efficiency. The average size of the prepared liposomes was between 574.67 ± 37.29 and 660.47 ± 44.32 nm. Positively charged liposomes (F1 and F3) exhibited a lower PDI than the corresponding neutrally charged ones (F2 and F4). Entrapment efficiency was higher in the neutral liposomes when compared to the charged formulation. F1 showed the lowest IC50 against HepG2, HCT116, and MCF-7 cancer cells. HepG2 cells treated with F1 showed the highest level of inhibition of cell proliferation with no evidence of apoptosis. Cell cycle analysis showed an increase in the G1/G0 and S phases, along with a decrease in the G2/M phases in the cell lines treated with drug loaded positively charged liposomes when compared to free positive liposomes, indicating arrest of cells in the S phase due to the stoppage of priming and DNA synthesis outside the mitotic phase. As a result, liposomes could be considered as an effective drug delivery system for treatment of a variety of cancers; they provide a chance that a nanoformulation of 6-MP will boost the cytotoxicity of the drug in a small pharmacological dose which provides a dosage advantage.

Drug delivery systems for treatment of temporomandibular joint osteoarthritis.

The number of people suffering from temporomandibular joint osteoarthritis (TMJOA) has been increasing. TMJOA cause joint noise, pain on TMJ and/or masticatory muscles, and restricted mandibular movement, which disturb eating, laughing and conversation, and impose serious lifestyle impediments. Chondrocyte apoptosis, extracellular matrix degradation, synovitis, and subchondral bone remodeling are the main pathological features of TMJOA. Various drug delivery systems are developed to controlled release at specific activation sites with high bioactivity and inhibit rapid dilution to enable long-term therapeutic response, which present great potential for the treatment of TMJOA. This review focuses on recently developed drug delivery systems by different administration in the TMJOA treatment, and summarizes their effects, duration, safety, and limitations, which would pave the way for development of TMJOA therapy.

Neurosurgically-Applied Chemotherapy for Childhood Brain Tumours Arising in the Posterior Fossa Using a Biodegradable Paste

Abstract AIMS This project aims to develop a local drug delivery system for treatment of childhood medulloblastoma (MB) and atypical teratoid/rhabdoid tumours (AT/RT), malignant brain neoplasms occurring in the posterior fossa for which prognoses remains poor. Our goal is to repurpose drug compounds reported as effective against MB and AT/RT, but which either cannot cross the blood-brain-barrier (BBB) or have not been assessed for localised delivery. We have developed a novel intra-cavity drug delivery system, consisting of polymer microparticles made from poly(DL-lactic-co-glycolic acid) and poly(ethylene glycol) (PLGA/PEG) which will be employed to release drugs over several weeks. METHOD Cell toxicity assays were undertaken using drugs of interest against an in vitro panel of relevant MB and AT/RT cell lines. PLGA/PEG paste incorporating the drugs were prepared and release kinetics assessed. RESULTS IC50 values of the drugs were assessed across all cell lines and a range of potencies were observed, with optimum conditions identified as dual treatments of PG545 (heparanse inhibitor) with CHIR99021 (glycogen synthase kinase-3 inhibitor) for MB and ribavirin (anti-viral) with CHIR99021 for AT/RT. Importantly, it was noted that the drugs retained their cytotoxicity following release from PLGA/PEG. Furthermore, release kinetics were finely tuned through careful control of the composition through addition of excipients and encapsulation of drugs in nanoparticles, and a library of formulations were prepared. CONCLUSION A local drug delivery system for MB and AT/RT has been developed and an optimum formulation, based upon in vitro cell assays and release kinetics, has been identified for in vivo efficacy studies in orthotopic models.