Delivery System For Treatment Research Articles

Drug Delivery Strategies for the Treatment of Pancreatic Cancer.

Pancreatic cancer is fast becoming a global menace and it is projected to be the second leading cause of cancer-related death by 2030. Pancreatic adenocarcinomas, which develop in the pancreas' exocrine region, are the predominant type of pancreatic cancer, representing about 95% of total pancreatic tumors. The malignancy progresses asymptomatically, making early diagnosis difficult. It is characterized by excessive production of fibrotic stroma known as desmoplasia, which aids tumor growth and metastatic spread by remodeling the extracellular matrix and releasing tumor growth factors. For decades, immense efforts have been harnessed toward developing more effective drug delivery systems for pancreatic cancer treatment leveraging nanotechnology, immunotherapy, drug conjugates, and combinations of these approaches. However, despite the reported preclinical success of these approaches, no substantial progress has been made clinically and the prognosis for pancreatic cancer is worsening. This review provides insights into challenges associated with the delivery of therapeutics for pancreatic cancer treatment and discusses drug delivery strategies to minimize adverse effects associated with current chemotherapy options and to improve the efficiency of drug treatment.

Research Advances in Nucleic Acid Delivery System for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that affects the lives of nearly 1% of the total population worldwide. With the understanding of RA, more and more therapeutic drugs have been developed. However, lots of them possess severe side effects, and gene therapy may be a potential method for RA treatment. A nanoparticle delivery system is vital for gene therapy, as it can keep the nucleic acids stable and enhance the efficiency of transfection in vivo. With the development of materials science, pharmaceutics and pathology, more novel nanomaterials and intelligent strategies are applied to better and safer gene therapy for RA. In this review, we first summarized the existing nanomaterials and active targeting ligands used for RA gene therapy. Then, we introduced various gene delivery systems for RA treatment, which may enlighten the relevant research in the future.

Levofloxacin HCl-Incorporated Zein-Based Solvent Removal Phase Inversion In Situ Forming Gel for Periodontitis Treatment.

Zein is composed of nonpolar amino acids and is a water-insoluble protein used as the matrix-forming agent of localized in situ forming gel (ISG). Therefore, this study prepared solvent removal phase inversion zein-based ISG formulations to load levofloxacin HCl (Lv) for periodontitis treatment using dimethyl sulfoxide (DMSO) and glycerol formal (GF) as the solvents. Their physicochemical properties were determined, including viscosity, injectability, gel formation, and drug release. The topography of dried remnants after drug release was revealed using a scanning electron microscope and X-ray computed microtomography (μCT) to investigate their 3D structure and % porosity. The antimicrobial activities were tested against Staphylococcus aureus (ATCC 6538), Escherichia coli ATCC 8739, Candida albicans ATCC 10231, and Porphyromonas gingivalis ATCC 33277 with agar cup diffusion. Increasing zein concentration or using GF as the solvent notably enhanced the apparent viscosity and injection force of the zein ISG. However, its gel formation slowed due to the dense zein matrix barrier's solvent exchange: the higher loaded zein or utilization of GF as an ISG solvent prolonged Lv release. The SEM and μCT images revealed the scaffold of dried ISG in that their % porosity corresponded with their phase transformation and drug release behavior. In addition, the sustainability of drug diffusion promoted a smaller antimicrobial inhibition clear zone. Drug release from all formulations was attained with minimum inhibitory concentrations against pathogen microbes and exhibited a controlled release over 7 days. Lv-loaded 20% zein ISG using GF as a solvent exhibited appropriate viscosity, Newtonian flow, acceptable gel formation and injectability, and prolonged Lv release over 7 days with efficient antimicrobial activities against various test microbes; thus, it is the potential ISG formulation for periodontitis treatment. Consequently, the Lv-loaded solvent removal zein-based ISGs proposed in this investigation offer promising potential as an efficacious drug delivery system for periodontitis treatment by local injection.

Tumor Microenvironment-Responsive 6-Mercaptopurine-Releasing Injectable Hydrogel for Colon Cancer Treatment

Colon cancer is a significant health concern. The development of effective drug delivery systems is critical for improving treatment outcomes. In this study, we developed a drug delivery system for colon cancer treatment by embedding 6-mercaptopurine (6-MP), an anticancer drug, in a thiolated gelatin/polyethylene glycol diacrylate hydrogel (6MP-GPGel). The 6MP-GPGel continuously released 6-MP, the anticancer drug. The release rate of 6-MP was further accelerated in an acidic or glutathione environment that mimicked a tumor microenvironment. In addition, when pure 6-MP was used for treatment, cancer cells proliferated again from day 5, whereas a continuous supply of 6-MP from the 6MP-GPGel continuously suppressed the survival rate of cancer cells. In conclusion, our study demonstrates that embedding 6-MP in a hydrogel formulation can improve the efficacy of colon cancer treatment and may serve as a promising minimally invasive and localized drug delivery system for future development.

Hybrid Nanoparticle System Integrating Tumor-Derived Exosomes and Poly(amidoamine) Dendrimers: Implications for an Effective Gene Delivery Platform

Nanoscale drug delivery systems for cancer treatment have demonstrated promising results in enhancing the selectivity of therapeutic agents while reducing their toxic side effects. However, several biological and physical barriers, such as the immunogenicity and undesirable biodistributions of such delivery systems, have hindered their fast translation. To address these issues, we have developed an exosome–dendrimer hybrid nanoparticle (NP) platform to combine the advantageous biological properties of natural exosomes and synthetic dendrimers into a single NP system. The novel hybrid NPs, consisting of exosomes derived from MCF7 cells and functionalized poly(amidoamine) (PAMAM) dendrimers, were prepared using sonication and characterized in terms of loading efficiency, size, cytotoxicity, and cellular interactions. Our results indicate that the loading of dendrimers into exosomes is dependent on dendrimer size and charge. The hybrid NPs inherited the size (∼150 nm), surface charge (−10 mV), and surface protein markers (CD81 and CD63) of exosomes. Importantly, the hybrid NPs enhanced the cellular internalization of amine-terminated PAMAM dendrimers (p < 0.05) while exhibiting substantially lower cytotoxicity than the free positively charged dendrimers (113.3 vs 35.6% of cell viability at 500 nM, p < 0.05). These advantageous properties of hybrid NPs were leveraged for use as a gene delivery vehicle, resulting in enhanced oligonucleotide delivery (over 2-fold) to cancer cells, compared to dendrimers alone. Furthermore, the hybrid NPs effectively delivered small interfering RNA (siRNA) as well, downregulating programmed death-ligand 1 (PD-L1) expression significantly more (3.8-fold) than dendrimers alone (p < 0.05). Our results demonstrate that the individual characteristics of both exosomes and dendrimers can be integrated to generate a multifaceted NP platform, proposing a novel NP design strategy.

Designing and characterization of Yahom buccal mucoadhesive tablets for oral ulcer treatment

Oral ulcer is a common oral mucosal disease that affects about 5–20% of general population, particularly the elderly, and is characterized by recurrent, painful ulcerations and burning sensation. Various possible causes include local, systemic, immunologic, genetic, allergic and microorganisms. Yahom is a Thai traditional medicine that has long been used to treat nausea, vomiting, dizziness and weakness in elderly. Yahom is produced from a variety components of dried medicinal plant parts that are mostly ground into powder dosage form. Ingredients are composed of following crude drugs are common incorporated in Yahom preparations such as clove, terminalia gall, costus root and ceylon ironwood flower which practically and clearly exhibit the potent antioxidant and antimicrobial activities. Therefore, it is interesting to apply Yahom as active component for oral ulcer treatment using appropriate approach such as mucoadhesive tablet. The objective of this study is to develop buccal mucoadhesive tablet consisting of hydroxypropyl methylcellulose (HPMC) and polyvinyl pyrrolidone (PVP) as mucoadhesive polymers in formulations. The impact of various ratios of Yahom: polymer and polymer mixtures were investigated on physicochemical properties of mucoadhesive tablets were investigated including physical properties, disintegration time, water sorption/erosion behaviors and ex-vivo mucoadhesion. In addition, the antimicrobial activities of formulations against two standard microbes were also evaluated using agar cup diffusion methods. Yahom mucoadhesive tablets were successfully fabricated using direct compression tableting technique with good appearance and acceptable physical properties. Different amounts of Yahom and polymer ratios apparently influenced on water sorption, erosion behaviors and hardness of mucoadhesive tablets, resulting in alteration of disintegration time and muco-adhesion properties. In addition, these prepared tablets exhibited the efficient antimicrobial activities against Staphylococcus aureus ATCC 6538 and C. albicans ATCC 10231. Therefore, the buccal mucoadhesive tablets containing Yahom are the potential herbal delivery system for oral ulcer treatment.

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.

Design and Evaluation of Dissolvable Microneedles for Treating Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic inflammatory skin disease caused predominantly by immune dysregulation. The global impact of AD continues to increase, making it not only a significant public health issue but also a risk factor for progression into other allergic phenotype disorders. Treatment of moderate-to-severe symptomatic AD involves general skin care, restoration of the skin barrier function, and local anti-inflammatory drug combinations, and may also require systemic therapy, which is often associated with severe adverse effects and is occasionally unsuitable for long-term use. The main objective of this study was to develop a new delivery system for AD treatment based on dissolvable microneedles containing dexamethasone incorporated in a dissolvable polyvinyl alcohol/polyvinylpyrrolidone matrix. SEM imaging of the microneedles showed well-structured arrays comprising pyramidal needles, fast drug release in vitro in Franz diffusion cells, an appropriate mechanical strength recorded with a texture analyzer, and low cytotoxicity. Significant clinical improvements, including in the dermatitis score, spleen weights, and clinical scores, were observed in an AD in vivo model using BALB/c nude mice. Taken together, our results support the hypothesis that microneedle devices loaded with dexamethasone have great potential as a treatment for AD and possibly for other skin conditions as well.

In vitro evaluation of genipin-crosslinked gelatin hydrogels for vocal fold injection

Glottic insufficiency is one of the voice disorders affecting all demographics. Due to the incomplete closure of the vocal fold, there is a risk of aspiration and ineffective phonation. Current treatments for glottic insufficiency include nerve repair, reinnervation, implantation and injection laryngoplasty. Injection laryngoplasty is favored among these techniques due to its cost-effectiveness and efficiency. However, research into developing an effective injectable for the treatment of glottic insufficiency is currently lacking. Therefore, this study aims to develop an injectable gelatin (G) hydrogel crosslinked with either 1-ethyl-3-(3-dimethylaminpropyl)carbodiimide hydrochloride) (EDC) or genipin (gn). The gelation time, biodegradability and swelling ratio of hydrogels with varying concentrations of gelatin (6–10% G) and genipin (0.1–0.5% gn) were investigated. Some selected formulations were proceeded with rheology, pore size, chemical analysis and in vitro cellular activity of Wharton's Jelly Mesenchymal Stem Cells (WJMSCs), to determine the safety application of the selected hydrogels, for future cell delivery prospect. 6G 0.4gn and 8G 0.4gn were the only hydrogel groups capable of achieving complete gelation within 20 min, exhibiting an elastic modulus between 2 and 10 kPa and a pore size between 100 and 400 μm. Moreover, these hydrogels were biodegradable and biocompatible with WJMSCs, as > 70% viability were observed after 7 days of in vitro culture. Our results suggested 6G 0.4gn and 8G 0.4gn hydrogels as potential cell encapsulation injectates. In light of these findings, future research should focus on characterizing their encapsulation efficiency and exploring the possibility of using these hydrogels as a drug delivery system for vocal fold treatment.

Contact Lens as Drug Delivery System for Glaucoma Treatment: A Review

Background and Objective: Glaucoma is one of the leading causes of irreversible blindness globally and directly impacts optic nerve-altering vision. The condition has been linked to increased intraocular pressure (IOP). The objective of this review was to search how well different drug solutions containing gold nanoparticles (GNPs) work in treating glaucoma, with a focus on using contact lenses instead of regular eye drops. Materials and Methods: The methodology was structured to review different literature on ocular drugs used in contact lenses to investigate and determine their impact on intraocular pressure (IOP). Some of the intraocular drugs covered in the methodology include timolol, bimatoprost, pilocarpine, etc. The review focused on using gold nanoparticles (GNPs) infused with the solution in contact lenses for timolol. Results: The review found that timolol helps reduce intraocular pressure for the first two hours, but then the effect wears off. Moreover, gold nanoparticles infused with timolol solution on contact lenses improved IOP. GNPs in lenses increased the accumulation of timolol in ciliary muscles. Conclusion: Contact lenses with saturated drug solutions and GNPs have better bioavailability and release durations. Given its prolonged drug release time and bioavailability, the timolol solution relieves intraocular pressure better than other solutions. GNP-infused contact lenses with drug solutions have been found to treat glaucoma better than eye drops.

Cryo-Shocked Platelet Coupled with ROS-Responsive Nanomedicine for Targeted Treatment of Thromboembolic Disease.

Thrombolysis with tissue plasminogen activator (tPA) provides the most common therapy for ischemic stroke onset within the past 4.5 h. However, enhanced neutrophil infiltration and secondary blood-brain barrier injury caused by tPA administration have limited its therapeutic application, and tPA treatment is often accompanied by hemorrhagic transformation. To overcome the limitations of thrombolysis by tPA, maximize the therapeutic efficacy, and improve the safety, herein, we report a cryo-shocked platelet-based cell-hitchhiking drug delivery system, which consists of cryo-shocked platelet (CsPLT) and reactive oxygen species (ROS)-responsive liposomes loaded with thrombolytic tPA and anti-inflammation drug aspirin (ASA). CsPLT and liposomes were facilely conjugated via host-guest interactions. Under the guidance of CsPLT, it selectively accumulated in the thrombus site and quickly released the therapeutic payloads in response to the high ROS. tPA subsequently exhibited localized thrombolytic activity to suppress the expansion of thrombus, while ASA assisted in the inactivation of reactive astrogliosis, microglial/macrophage, and obstruction of neutrophil infiltration. This cryo-shocked platelet-hitchhiking tPA/ASA delivery system not only improves the thrombus-targeting efficiency of the two drugs for highly localized thrombolytic effects and anti-inflammation actions and platelets inactivation but also provides insights to the development of targeted drug delivery systems for thromboembolic disease treatment.

Ampicillin-resistant bacterial pathogens targeted chitosan nano-drug delivery system (CS-AMP-P-ZnO) for combinational antibacterial treatment

Drug-resistant microorganisms are defeated using combinational drug delivery systems based on biopolymer chitosan (CS) and metal nanoparticles. Hence, PEGylated zinc oxide nanoparticles (P-ZnO NPs) decorated chitosan-based nanoparticles (CS NPs) were prepared to deliver ampicillin (AMP) for improved antibacterial activity. In comparison to ZnO NPs, P-ZnO NPs exhibit less aggregation and more stable rod morphologies in TEM. The size of the P-ZnO NPs decreased and was engulfed by the spherical CS-AMP NPs. The zeta potential of the CS-AMP-P-ZnO NPs was determined to be −32.93 mV and the hydrodynamic size to be 210.2 d. nm. Further, DEE and DLE of CS-AMP (2.0:0.2 w/w) showed 79.60 ± 2.62 % and 15.14 ± 2.11 %, respectively. The cumulative AMP release was observed at >50 % at 48 h at pH 5.4 and 7.4. Additionally, when compared to AMP, CS-AMP-P-ZnO NPs had better antibacterial activity against E. coli, due to the alternation of cell membrane permeability by CS and ZnO NPs. Moreover, the hemolytic properties of ZnO NPs were attenuated because of PEGylation and CS. Furthermore, due to the biocompatible behavior of CS, CS-AMP-P-ZnO NPs did not exhibit toxicity on HEK-293 cells, erythrocytes, and chick embryos. Hence, this study concludes that CS-AMP-P-ZnO NPs could be a promising antibacterial agent.

Poly(amidoamine) Dendrimer/Camptothecin Complex: From Synthesis to In Vitro Cancer Cell Line Studies

Camptothecin (CPT), an alkaloid with potent anticancer activity, is still not used in clinical practice due to its high hydrophobicity, toxicity, and poor active-form stability. To address these shortcomings, our research focuses on the encapsulation of this drug in the poly(amidoamine) (PAMAM) dendrimer macromolecule. The PAMAM dendrimer/CPT complex was synthesized and thoroughly characterized. The in vitro drug release study revealed that the drug was released in a slow and controlled manner in acidic and physiological conditions and that more than 80% of the drug was released after 168 h of incubation. Furthermore, it was demonstrated that CPT was released with first-order kinetics and non-Fickian transport. The studies on the hemolytic activity of the synthesized complex indicated that it is hemocompatible for potential intravenous administration at a concentration ≤ 5 µg/mL. Additionally, the developed product was shown to reduce the viability of non-small-cell lung cancer cells (A549) in a concentration- and time-dependent manner, and cancer cells were more susceptible to the complex than normal fibroblasts. Lastly, molecular modeling studies revealed that the lactone or carboxylic forms of CPT had a significant impact on the shape and stability of the complex and that its formation with the lactone form of CPT was more energetically favorable for each subsequent molecule than the carboxylic form. The report represents a systematic and structured approach to develop a PAMAM dendrimer/CPT complex that can be used as an effective drug delivery system (DDS) for the potential treatment of non-small-cell lung cancer.

Brief review: Applications of nanocomposite in electrochemical sensor and drugs delivery.

The recent advancement of nanoparticles (NPs) holds significant potential for treating various ailments. NPs are employed as drug carriers for diseases like cancer because of their small size and increased stability. In addition, they have several desirable properties that make them ideal for treating bone cancer, including high stability, specificity, higher sensitivity, and efficacy. Furthermore, they might be taken into account to permit the precise drug release from the matrix. Drug delivery systems for cancer treatment have progressed to include nanocomposites, metallic NPs, dendrimers, and liposomes. Materials' mechanical strength, hardness, electrical and thermal conductivity, and electrochemical sensors are significantly improved using nanoparticles (NPs). New sensing devices, drug delivery systems, electrochemical sensors, and biosensors can all benefit considerably from the NPs' exceptional physical and chemical capabilities. Nanotechnology is discussed in this article from a variety of angles, including its recent applications in the medical sciences for the effective treatment of bone cancers and its potential as a promising option for treating other complex health anomalies via the use of anti-tumour therapy, radiotherapy, the delivery of proteins, antibiotics, and vaccines, and other methods. This also brings to light the role that model simulations can play in diagnosing and treating bone cancer, an area where Nanomedicine has recently been formulated. There has been a recent uptick in using nanotechnology to treat conditions affecting the skeleton. Consequently, it will pave the door for more effective utilization of cutting-edge technology, including electrochemical sensors and biosensors, and improved therapeutic outcomes.

Inorganic Nanosheet-Shielded Probiotics: A Self-Adaptable Oral Delivery System for Intestinal Disease Treatment.

The oral delivery of probiotics is commonly adopted for intestinal disease treatments in clinical settings; however, the probiotics suffer from a strong acidic attack in the gastric area and the low-efficiency intestinal colonization of naked probiotics. Coating living probiotics with synthetic materials has proven effective in enabling the adaption of bacteria to gastrointestinal environments, which, unfortunately, may shield the probiotics from initiating therapeutic responses. In this study, we report a copolymer-modified two-dimensional H-silicene nanomaterial (termed SiH@TPGS-PEI) that can facilitate probiotics to adapt to diverse gastrointestinal microenvironments on-demand. Briefly, SiH@TPGS-PEI electrostatically coated on the surface of probiotic bacteria helps to resist erosive destruction in the acidic stomach and spontaneously degrades by reacting with water to generate hydrogen, an anti-inflammatory gas in response to the neutral/weakly alkaline intestinal environment, thus exposing the probiotic bacteria for colitis amelioration. This strategy may shed new light on the development of intelligent self-adaptive materials.

In vivo toxicity evaluation of tumor targeted glycol chitosan nanoparticles in healthy mice: repeated high-dose of glycol chitosan nanoparticles potentially induce cardiotoxicity

BackgroundGlycol chitosan nanoparticles (CNPs) have emerged as an effective drug delivery system for cancer diagnosis and treatment. Although they have great biocompatibility owing to biodegradable chemical structure and low immunogenicity, sufficient information on in vivo toxicity to understand the potential risks depending on the repeated high-dose have not been adequately studied. Herein, we report the results of in vivo toxicity evaluation for CNPs focused on the number and dose of administration in healthy mice to provide a toxicological guideline for a better clinical application of CNPs.ResultsThe CNPs were prepared by conjugating hydrophilic glycol chitosan with hydrophobic 5β-cholanic acid and the amphiphilic glycol chitosan-5β-cholanic acid formed self-assembled nanoparticles with its concentration-dependent homogeneous size distributions (265.36–288.3 nm) in aqueous condition. In cell cultured system, they showed significantly high cellular uptake in breast cancer cells (4T1) and cardiomyocytes (H9C2) than in fibroblasts (L929) and macrophages (Raw264.7) in a dose- and time-dependent manners, resulting in severe necrotic cell death in H9C2 at a clinically relevant highly concentrated condition. In particular, when the high-dose (90 mg/kg) of CNPs were intravenously injected into the healthy mice, considerable amount was non-specifically accumulated in major organs (liver, lung, spleen, kidney and heart) after 6 h of injection and sustainably retained for 72 h. Finally, repeated high-dose of CNPs (90 mg/kg, three times) induced severe cardiotoxicity accompanying inflammatory responses, tissue damages, fibrotic changes and organ dysfunction.ConclusionsThis study demonstrates that repeated high-dose CNPs induce severe cardiotoxicity in vivo. Through the series of toxicological assessments in the healthy mice, this study provides a toxicological guideline that may expedite the application of CNPs in the clinical settings.

A multiple controlled-release hydrophilicity minocycline hydrochloride delivery system for the efficient treatment of periodontitis

The complexity of periodontitis, including the complex formation mechanisms and the complex periodontium physiological environment, as well as the complex association with multiple complications, often results in poor therapy effects. Herein, we aimed to design a nanosystem with a controlled release of minocycline hydrochloride (MH) and good retention to effectively treat periodontitis by inhibiting inflammation and repairing the alveolar bone. Firstly, insoluble ion-pairing (IIP) complexes were constructed to improve the encapsulation efficiency of hydrophilic MH in PLGA nanoparticles. Then, a nanogenerator was constructed and combined with a double emulsion method to encapsulate the complexes into PLGA nanoparticles (MH-NPs). The average particle size of MH-NPs was about 100 nm as observed by AFM and TEM, and the drug loading and encapsulation efficiency were 9.59% and 95.58%, respectively. Finally, a multifunctional system (MH-NPs-in-gels) was prepared by dispersing MH-NPs into thermosensitive gels, which could continue to release drug for 21 days in vitro. And the release mechanism showed that this controlled release behavior for MH was influenced by the insoluble ion-pairing complex, PLGA nanoparticles, and gels. In addition, the periodontitis rat model was established to investigate the pharmacodynamic effects. After 4 weeks of treatment, changes in the alveolar bone were assessed by Micro-CT (BV/TV: 70.88%; BMD: 0.97 g/cm3; TB.Th: 0.14 mm; Tb.N: 6.39 mm−1; Tb.Sp: 0.07 mm). The mechanism of MH-NPs-in-gels in vivo was clarified by the analysis of pharmacodynamic results, which showed that insoluble ion-pairing complexes with the aid of PLGA nanoparticles and gels achieved significant anti-inflammatory effects and bone repair capabilities. In conclusion, the multiple controlled-release hydrophilicity MH delivery system would have good prospects for the effective treatment of periodontitis.

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.

Control release of α-mangostin by a novel dual-polysaccharides delivery system for colitis treatment under simulated gastrointestinal conditions

The poor hydrophilia and strong cytotoxicity of α-mangostin, a major component of xanthones from pericarps of mangosteen (Garcinia Mangostana L.), restrict its application in functional food. To overcome its shortage, a series of alginate/xanthan gum or alginate/κ-carrageenan hydrogels loaded with α-mangostin were fabricated and their anti-inflammatory effects were investigated under gastrointestinal tract (GIT). With the increased concentration of polysaccharides, the release of α-mangostin was slower due to denser microstructure and hardness. The digestive profile suggested that the release of α-mangostin in 0.3% alginate/0.15% xanthan gum (0.15%X-αM), 0.3% alginate/0.2% xanthan gum (0.25%X-αM) and 0.3% alginate/0.3% κ-carrageenan (0.3%C-αM) hydrogels were faster than the others. The cytotoxicity of α-mangostin loaded in hydrogels was dramatically reduced. However, the anti-inflammatory effect of the three intestinal digestive fluids was still maintained at 71.9% ± 1.2%, 83.1% ± 2.0%, and 70.6% ± 3.3% in LPS-induced Raw246.7 cells. In addition, the three intestinal digestive fluids (50 μM of α-mangostin) showed good inhibition of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and the expression of iNos and Cox-2 respectively. Given these data, xanthan gum/κ-carrageenan-alginate composite hydrogels can be a good colonic target delivery system for bioactive compounds, which can be applied in functional foods to improve human health and wellness.

Early experience with UGN-101 for the treatment of upper tract urothelial cancer - A multicenter evaluation of practice patterns and outcomes.

UGN-101 is a novel delivery system for intracavitary treatment of upper tract urothelial cancer (UTUC). UGN-101 was approved based on a pivotal trial for small volume residual low-grade UTUC. Our aim was to report our experience with UGN-101 in a more heterogenous and real-world setting. We performed a retrospective review of all UGN-101 cases from 15 institutions with a focus on practice patterns, efficacy, and adverse effects. We include UGN-101 utilization in both the chemoablative and adjuvant setting. There were a total 136 renal units treated from 132 patients. The majority of cases were biopsy proven low-grade UTUC. Practice patterns varied considerably - the most common administration technique was antegrade instillation via a percutaneous nephrostomy. When utilized in the adjuvant setting, 69% of patients were disease free at the time of their first endoscopic evaluation, while in the chemoablative setting, 37% were endoscopically clear on the first evaluation (P < 0.001). Complete response was higher in patients with smaller tumor size prior to UGN-101 induction; low volume (<1 cm) residual disease was associated with a 70% complete response, similar to disease free rate at first endoscopic evaluation when UGN-101 was used in the adjuvant setting. The use of maintenance doses of UGN-101 was reported in 27% of cases. The overall incidence of new onset, clinically significant ureteral stenosis was 23%. This study represents the largest review of patients treated with UGN-101 and can serve as a basis of ongoing hypotheses regarding treatment with UGN-101 for UTUC.