ABSTRACT
Recent advancements in nanotechnology have resulted in improved medicine delivery to the target site. Nanosponges are three-dimensional drug delivery systems that are nanoscale in size and created by cross-linking polymers. The introduction of Nanosponges has been a significant step toward overcoming issues such as drug toxicity, low bioavailability, and predictable medication release. Using a new way of nanotechnology, nanosponges, which are porous with small sponges (below one microm) flowing throughout the body, have demonstrated excellent results in delivering drugs. As a result, they reach the target place, attach to the skin's surface, and slowly release the medicine. Nanosponges can be used to encapsulate a wide range of medicines, including both hydrophilic and lipophilic pharmaceuticals. The medication delivery method using nanosponges is one of the most promising fields in pharmacy. It can be used as a biocatalyst carrier for vaccines, antibodies, enzymes, and proteins to be released. The existing study enlightens on the preparation method, evaluation, and prospective application in a medication delivery system and also focuses on patents filed in the field of nanosponges.Copyright © 2023 The Authors.
ABSTRACT
Biodegradable polymeric blends are used to study the controlled release of Hydroxychloroquine sulphate (HCQ) as the model drug used extensively in COVID-19 treatments. HCQ drug is loaded in sodium alginate (NaAlg) and lignosulphonic acid (NaLS) blends as matrix are crosslinked using calcium chloride solution. Its release is evaluated in different pH mediums of simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The HCQ release data obtained during experimentation is used to study kinetics using different models to investigate polymeric relaxation's drug diffusion and mechanism in water-soluble HCQ drug. The drug release mechanism best fits the Higuchi model with Fickian diffusion as the primary polymeric relaxation mechanism. © 2023, Walailak University. All rights reserved.
ABSTRACT
The recent remarkable success and safety of mRNA lipid nanoparticle technology for producing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines has stimulated intensive efforts to expand nanoparticle strategies to treat various diseases. Numerous synthetic nanoparticles have been developed for pharmaceutical delivery and cancer treatment. However, only a limited number of nanotherapies have enter clinical trials or are clinically approved. Systemically administered nanotherapies are likely to be sequestered by host mononuclear phagocyte system (MPS), resulting in suboptimal pharmacokinetics and insufficient drug concentrations in tumors. Bioinspired drug-delivery formulations have emerged as an alternative approach to evade the MPS and show potential to improve drug therapeutic efficacy. Here we developed a biodegradable polymer-conjugated camptothecin prodrug encapsulated in the plasma membrane of lipopolysaccharide-stimulated macrophages. Polymer conjugation revived the parent camptothecin agent (e.g., 7-ethyl-10-hydroxy-camptothecin), enabling lipid nanoparticle encapsulation. Furthermore, macrophage membrane cloaking transformed the nonadhesive lipid nanoparticles into bioadhesive nanocamptothecin, increasing the cellular uptake and tumor-tropic effects of this biomimetic therapy. When tested in a preclinical murine model of breast cancer, macrophage-camouflaged nanocamptothecin exhibited a higher level of tumor accumulation than uncoated nanoparticles. Furthermore, intravenous administration of the therapy effectively suppressed tumor growth and the metastatic burden without causing systematic toxicity. Our study describes a combinatorial strategy that uses polymeric prodrug design and cell membrane cloaking to achieve therapeutics with high efficacy and low toxicity. This approach might also be generally applicable to formulate other therapeutic candidates that are not compatible or miscible with biomimetic delivery carriers. © 2022 The Authors
ABSTRACT
Biomimetic strategies can be adopted to improve biopharmaceutical aspects. Subsequently, Biomimetic reconstitutable pegylated amphiphilic lipid nanocarriers have high translational potential for systemic controlled drug delivery;however, such an improvised system for systemic aspirin delivery exploring nanotechnology is not available. Systemic administration of aspirin and its controlled delivery can significantly control blood clotting events, leading to stroke, which has immediate applications in cardiovascular diseases and Covid-19. In this work, we are developing aspirin sustained release pegylated amphiphilic self-assembling nanoparticles to develop reconstitutable aspirin injections by solvent-based co-precipitation method with phase inversion technique that leads to novel "biomimetic niosomal nanoparticles (BNNs).” DOE led optimization is done to develop Design of space for optimized particles. Upon reconstitution of solid powder, the particle size was 144.8 ± 12.90 nm with a surface charge of -29.2 ± 2.24 mV. The entrapment efficiency was found to be 49 ± 0.15%, wherein 96.99 ± 1.57% of the drug was released in 24hr showing super case II transport-based drug release mechanism. The formulation has the least hemolysis while showing significant suppression of platelet aggregation. MTT assay does not show any significant cytotoxicity. This is a potential nanoparticle that can be explored for developing aspirin injection, which is not available.
ABSTRACT
The global anxiety and economic crisis causes the deadly pandemic coronavirus disease of 2019 (COVID 19) affect millions of people right now. Subsequently, this life threatened viral disease is caused due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, morbidity and mortality of infected patients are due to cytokines storm syndrome associated with lung injury and multiorgan failure caused by COVID 19. Thereafter, several methodological advances have been approved by WHO and US-FDA for the detection, diagnosis and control of this wide spreadable communicable disease but still facing multi-challenges to control. Herein, we majorly emphasize the current trends and future perspectives of nano-medicinal based approaches for the delivery of anti-COVID 19 therapeutic moieties. Interestingly, Nanoparticles (NPs) loaded with drug molecules or vaccines resemble morphological features of SARS-CoV-2 in their size (60–140 nm) and shape (circular or spherical) that particularly mimics the virus facilitating strong interaction between them. Indeed, the delivery of anti-COVID 19 cargos via a nanoparticle such as Lipidic nanoparticles, Polymeric nanoparticles, Metallic nanoparticles, and Multi-functionalized nanoparticles to overcome the drawbacks of conventional approaches, specifying the site-specific targeting with reduced drug loading and toxicities, exhibit their immense potential. Additionally, nano-technological based drug delivery with their peculiar characteristics of having low immunogenicity, tunable drug release, multidrug delivery, higher selectivity and specificity, higher efficacy and tolerability switch on the novel pathway for the prevention and treatment of COVID 19. © 2022 The Author(s)
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Steroidal products have been found useful in inflammations associated with Covid 19. Prednisolone is one readily available steroid, which is often found as uncoated normal release tablets. Modified release prednisolone may be desirable in Covid 19 for sustained actions. This is expected to reduce dosing frequency and enhance compliance. This study is concerned with development of controlled release prednisolone using coating technology with bio-compatible, cross-linked starch-albumin films. Starches and proteins are excellent film formers with good flexibility, transparency, and bio-compatibility. The cross-linked starch-albumin films were prepared using glycerol as the plasticizer: starch (A), starch-albumin (B), starch-albumin cross-linked with formaldehyde at 1 % (C), 5 % (D) and 10 % (E). Equilibrium moisture sorption (EMS) at 100 % relative humidity, equilibrium swelling (ESC) in buffer solutions of pHs 2, 7 and 9, and DSC thermal properties were evaluated. In-vitro drug release from the film coated prednisolone tablets were evaluated in 0.1N HCl, water and phosphate buffer 8.0 as dissolution media. Films showed ESC in the order A>D>E>B>C;D>C>A>E>B and A>D>C>B>E in acidic, neutral and alkali media respectively. EMS was in the order B>E>A>D>C;with slight shift in the melting temperatures. In-vitro release at 240 min varied from 78 to 117 % (E>D>C>A>B);19 to 60 % (D>B>C>E>A) and 49 to 60 % (B>A>C>D>E) in 0.1N HCl, water and PBS respectively. Cross-linking improved the stability and swelling of films. The in-vitro release in alkaline medium suggests their usefulness for controlled drug delivery. New pH-responsive polymers, with improved physicochemical properties for coating prednisolone tablets were developed. Copyright © 2007, Nat. Inst. for Pharmaceutical Research and Development. All rights reserved.
ABSTRACT
BACKGROUND: The efficacy of topical corticosteroids is limited in chronic rhinosinusitis (CRS) due to rapid clearance from the nasal cavity and insufficient drug delivery to inflamed sinonasal passages. LYR-210 is an implantable corticosteroid matrix designed to provide up to 24 weeks of treatment to patients with CRS by locally delivering mometasone furoate (MF) to the sinonasal mucosa. In a randomized, controlled, dose-ranging LANTERN study, LYR-210 (7500 µg) achieved clinically relevant improvement in CRS cardinal symptom composite scores, the 22-item Sinonasal Outcome Test (SNOT-22), ethmoid opacification, and the need for rescue treatment at 24 weeks. OBJECTIVE: As the plasma MF concentrations of LYR-210 (2500 µg) and LYR-210 (7500 µg) were evaluated at weeks 4, 12, and 24 in the LANTERN study (data on file at Lyra Therapeutics, Inc.), this study aims to characterize the pharmacokinetic profiles of both doses of LYR-210 at earlier timepoints post-placement in patients with CRS. METHODS: Twenty-four surgically naïve adult patients with CRS were enrolled in an open-label, multicenter study and underwent in-office bilateral administration of LYR-210 (2500 µg) (n = 12 patients) or LYR-210 (7500 µg) (n = 12 patients) into the middle meatus. Plasma MF concentrations were determined pre-placement and 1-h post-placement (day 1), and on days 2, 3, 7, 14, 21, 28, 42, and 56 by liquid chromatography-tandem mass spectrometry. RESULTS: Both LYR-210 doses were well-tolerated with no serious adverse events. Systemic MF levels were dose-dependent and lower than reported values of other respiratory MF products. Plasma MF concentrations showed steady drug release from LYR-210 (2500 µg) and LYR-210 (7500 µg) that persisted through day 56. CONCLUSION: LYR-210 achieved dose-dependent, continuous local MF delivery at a steady rate with low systemic exposure for months.
Subject(s)
Pregnadienediols , Sinusitis , Adrenal Cortex Hormones/therapeutic use , Adult , Chronic Disease , Drug Liberation , Humans , Mometasone Furoate/therapeutic use , Pharmaceutical Preparations , Pregnadienediols/adverse effects , Pregnadienediols/pharmacokinetics , Sinusitis/drug therapy , Treatment OutcomeABSTRACT
Viral infections cause damage to various organ systems by inducing organ-specific symptoms or systemic multi-organ damage. Depending on the infection route and virus type, infectious diseases are classified as respiratory, nervous, immune, digestive, or skin infections. Since these infectious diseases can widely spread in the community and their catastrophic effects are severe, identification of their causative agent and mechanisms underlying their pathogenesis is an urgent necessity. Although infection-associated mechanisms have been studied in two-dimensional (2D) cell culture models and animal models, they have shown limitations in organ-specific or human-associated pathogenesis, and the development of a human-organ-mimetic system is required. Recently, three-dimensional (3D) engineered tissue models, which can present human organ-like physiology in terms of the 3D structure, utilization of human-originated cells, recapitulation of physiological stimuli, and tight cell-cell interactions, were developed. Furthermore, recent studies have shown that these models can recapitulate infection-associated pathologies. In this review, we summarized the recent advances in 3D engineered tissue models that mimic organ-specific viral infections. First, we briefly described the limitations of the current 2D and animal models in recapitulating human-specific viral infection pathology. Next, we provided an overview of recently reported viral infection models, focusing particularly on organ-specific infection pathologies. Finally, a future perspective that must be pursued to reconstitute more human-specific infectious diseases is presented. Copyright © 2022 The Authors
ABSTRACT
A table-top microdevice was introduced in this work to produce ultrasmall particles for drug delivery via inhalation. The design and operation are similar to that of spray-drying equipment used in industry, but the device itself is much smaller and more portable in size, simpler to operate and more economical. More importantly, the device enables more accurate control over particle size. Using Flavopiridol, an anti-inflammation medication, formulations have been developed to produce inhalable particles for pulmonary delivery. A solution containing the desired components forms droplets by passing through an array of micro-apertures that vibrate via a piezo-electrical driver. High-purity nitrogen gas was introduced and flew through the designed path, which included the funnel collection and cyclone chamber, and finally was pumped away. The gas carried and dried the micronized liquid droplets along the pathway, leading to the precipitation of dry solid microparticles. The formation of the cyclone was essential to assure the sufficient travel path length of the liquid droplets to allow drying. Synthesis parameters were optimized to produce microparticles, whose morphology, size, physio-chemical properties, and release profiles met the criteria for inhalation. Bioactivity assays have revealed a high degree of anti-inflammation. The above-mentioned approach enabled the production of inhalable particles in research laboratories in general, using the simple table-top microdevice. The microparticles enable the inhalable delivery of anti-inflammation medicine to the lungs, thus providing treatment for diseases such as pulmonary fibrosis and COVID-19.
ABSTRACT
Background: Obesity is a chronic and relapsing disease, with a rising prevalence and a high economic burden. Obesity is a risk factor for COVID-19 infection severity and mortality. Anti-obesity medications (AOMs) are safe and effective for weight loss. However, weight loss outcomes with AOMs during the COVID-19 pandemic are yet to be described. We hypothesized that weight loss outcomes with AOMs during COVID-19 are inferior to those before this period. Methods: We performed a systematic review of electronic medical record of patients from the Mayo Clinic Health System. We included all patients who started a long-term FDA-approved AOM (phentermine-topiramate extended release [PHEN-TOP], naltrexone-bupropion sustained release [NBSR], and liraglutide 3.0 mg). We excluded patients with a history of bariatric surgery or endoscopic procedure, those taking ≥2 AOMs, ≥3 months of prescribed AOM, and/or pregnancy. Demographic and anthropometric data were ed from in person or virtual encounters. Analysis was divided by 1) those who started an AOM at least a year before COVID-19 restrictions were set in place in the USA (i.e. first quarter of 2019 period or earlier, defined as “PreCOVID-19”), and 2) those who started an AOM during or after the first quarter of 2020, (defined as “COVID-19''). We calculated the total body weight loss percentage (TBWL%) at 3, 6, and 12 months after AOM initiation along with the percentage of patients who achieved a TBWL ³5% and ³10%, after one year of starting an AOM. Our primary endpoint was the TBWL% at 12 months. All tests were two-tailed and p-value <0.05 was considered statistically significant. Values are presented as mean ± standard deviation (SD). Results: A total of 249 patients were included in the analysis (77% female, age 48.8±12.6 years, body-mass index [BMI] 41.9±8.6 kg/m2). There were no differences in baseline characteristics between both groups (Table 1). Fifty-five percent of the patients were prescribed PHEN-TOP, 16% NBSR, and 29% liraglutide. There was a statistical difference in TBWL% between the PreCOVID-19 group compared to the COVID-19 group: 5.3±3.5% vs 4±3.7% (p=0.03) and 9.6±7% vs 6.5±5.3% (p=0.02) at 3 and 12 months, respectively (Fig. 1A). After 1 year follow-up, 53.6% of patients in the COVID-19 group achieved >5% TBWL compared with 75.3% in the PreCOVID-19 group (p=0.04), and 17.9% of patients in the COVID-19 group achieved 105% TBWL compared with 44.7% in the PreCOVID-19 group (p=0.01) (Fig. 1B). Conclusion: This study shows that weight loss outcomes to AOMs were inferior when prescribed during COVID-19 pandemic, compared to the outcomes observed prior to this. Further studies are needed to understand whether this observation is due to changes in care delivery during the pandemic or due to individual factors such as stress, decreased physical activity, remote working, among others.(Table Presented)Table 1. The demographic, antiobesity medications, and weight loss outcome distribution among patients Pre- and COVID-19.(Figure Presented) Figure 1. The weight loss outcomes of patients (Pre and COVID-19) after one year of AOM therapy (A). The distribution of patients (Pre and COVID-19) achieving >5% and >10% TBWL following one year of AOM (B).
ABSTRACT
Background: Nasal route of drug administration has gained popularity nowadays specially for drugs acting on nasopulmonary area. Atazanavir is an antiviral drug which has proved efficacy in different viral infection including COVID-19. Therefore the hypothesis is, if given through intra nasal route this formulation will be able to prevent the viral infection like COVID-19 by directly acting on the virus at its entry point. Objectives: This study aims to prepare a stable mucoadhesive microcrystal formulation of this antiviral drug with good permeation for intra nasal delivery. Materials and Methods: The formulation was prepared by high-speed homogenization process. Prepared microcrystals were estimated for in vitro drug release and permeation, drug excipient interaction study by DSC, FTIR and in vitro mucoadhesiveness study on agar gel plate. A short-term stability study was conducted on all formulations for 6 months. Results: The melting point and absorbance maxima of atazanavir were found as 200.9°C and 248 nm. The DSC and FTIR study results confirmed no drug excipient interaction was there in the formulation. The particle size of the formulations was found as 5-11 µm in range. Drug release was better and faster from the microcrystals as compare to pure powder drug. The flux for microcrystal formulation was found to be 100 whereas flux for the pure drug powder was 24. Formulations had sufficient mucoadhesive strength due to incorporation of HPMC 400 polymer and they were found stable after six months stability study. Conclusion: Lastly, it can be concluded that this formulation would be a promising system for the delivery through intra nasal route as it showed good drug release and permeation during a short time span in in vitro nasal condition with a particle size range suitable for intranasal delivery. However, further in vivo studies are required to confirm the hypothesis.
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One option to improve tissue regeneration is the use of growth factors. As a promising alternative to recombinant protein therapy, gene therapy allows local and sustained release of growth factors. This moderate and constant release is more suitable for regenerative processes compared to administration of high protein doses. Exogenous growth factors are produced by cells in situ;such highly bioactive amounts of growth factors are produced directly at the defect site, thereby highly limiting adverse off-target effects. Targeted research areas include (combinatorial) gene therapy approaches for bone/musculoskeletal tissue regeneration in vivo and ex vivo. Amongst them, new techniques such as viral and non-viral gene delivery systems, next-generation therapeutical DNA vectors for example with decreased immunogenicity, enhanced bioactivity of growth factor and enhanced gene expression. Beside DNA based gene therapy also mRNA based technologies are increasingly used and becoming popular by Covid vaccination successes. Increasing records of clinical success in the last years have constantly improved awareness of gene therapy, strengthening the enthusiasm of the community for novel and effective treatment methods providing the needed momentum for further developments.
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Excipients are critically important in converting active pharmaceutical ingredients (API) into drug products that have optimal stability, bioavailability, manufacturability, duration of action, and therapeutic benefits. They will play even greater roles in the future to enable drug targeting, delivery of biotech products and vaccines, gene therapy, continuous manufacturing, 3D printing, and so forth. This commentary describes the author’s experience in teaching a graduate course on excipients at St. John’s University to train students on optimal selection and appropriate use of excipients in formulating dosage forms and development of drug delivery systems. The course is offered in 15 two-hour sessions over a semester, and the course materials are divided into 13 modules on chemistry of different classes of polymeric and non-polymeric excipients and their application in dosage form development, including the use as solubilizing agents, lyophilizing agents, cryoprotectants, buffers, biodegradable materials, and carriers for amorphous solid dispersions and 3D printing. The development of coprocessed excipients, the need for new excipients, and the regulatory aspects of excipients are also covered. The course includes presentations by guest speakers from the industry, and the students also watch virtual presentations from experts that are publicly available from the internet. It is a popular course at St. John’s University taken by all graduate students in the pharmaceutics program. It is recommended that such courses are introduced in other pharmacy schools and academic institutions. The course may be adapted to meet specific needs of different academic programs. Professional associations, such as AAPS and CRS, industry groups like IPEC, and the pharmaceutical industry may be able to help in introducing such courses by providing lecture materials and guest lecturers.
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The work led to the formulation of a powder of calcium phosphate coated liposomes containing cyclosporine A (CsA). The formulation was designed to reduce the dose of CsA to be administered following lung transplantation. Potentially this formulation can be used also to contain the inflammatory process due to SARS-CoV-2. Calcium phosphate (CaP) is a material found in bones and teeth and considered non-toxic and biocompatible and this coating could reduce the recognition by alveolar macrophages and increase the cell uptake. Moreover, CaP is insoluble at physiological pH (7.4), while it solubilizes easily at pH below 5. This could favor drug release in the cell after pinocytosis and in inflamed tissues, while reducing drug release at physiological pH [1]. The liposomes produced were evaluated in terms of size, surface charge and drug loading. The presence of the CaP coating was verified by calcium titration, variation of the zeta potential and by cryogenic transmission electron microscopy (cryo-TEM). The highest loading was obtained in the formulation containing CsA at 7% (w/w). Cholesterol was added to liposomes at two different concentrations in order to improve the stability of the nanostructure and reduce the drug leakage. However, cholesterol did not bring any improvement to the formulation. The inhalation powder produced by spray drying with the best aerosolization performance (fine particle fraction of coated liposomes powder 33.69 - 1.6% and 50.50- 0.6% for the uncoated liposomes powder) was obtained using a 1:3 weight ratio between liposomes and excipients using mannitol as bulking agent and 15% L-leucine. Key Message: This work aimed to develop a respirable dry powder for inhalation containing CsA for the local treatment of lung immune diseases. CsA was efficiently loaded into CaP-coated liposomes and transformed into a respirable powder by spray-drying. The inhaled immunosuppressive product would offer multiple advantages related to drug deposition at the target site. Furthermore, the coating of the liposomes governs the release of the drug which will occur only at only at biological acidic conditions.
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Layered double hydroxide nanomaterials (LDH NMs) have been dragging the researchers' attention toward biomedical applications owing to their physiochemical properties, biocompatibility, environmental sensitivity and good cellular uptake mechanisms. Various synthetic methods have been presented in brief. This paper draws attention toward the modification and functionalization of LDH nanostructures for biomedical applications in targeted and controlled drug release, anticancer, bioimaging, bone therapy and regeneration, gene delivery, ophthalmic and antitumor activities. Further, it explains the properties of conjugated LDH NMs which put forward their possibilities to be used in synthesizing the most demanding vaccine for COVID-19 pandemic. Current scenario, challenges and future perspective of LDH NMs have also been discussed.