Retention Time Of Drug Research Articles

The impact of COVID-19 and other factors on the usage status of the biologic drug therapies for rheumatoid arthritis: A study from Vietnam

ObjectivesTo describe the status of using biological Disease Modifying Anti Rheumatic Drugs (bDMARDs) to treat rheumatoid arthritis (RA) and related factors. In addition, the study determined the impact of COVID-19 on the usage of bDMARDs. MethodsThis is a cross-sectional study and included 219 RA patients over 18 years old. The Kaplan–Meier method and the log-rank test (p<0.05) were used to estimate the retention time and compare between different times. Cox regression analysis was used to determine the factors affecting the retention time of biological drugs (p<0.05). ResultsOut of 1967 courses of treatment, there were 149 (7.6%) drug discontinuations, 760 (38.6%) doses extensions and 64 (3.3%) drug switch. Moderate disease level and choosing tumor necrosis factor (TNF) inhibitors initially were associated with retention time of COVID-19. Drug discontinuations and dose extensions increased after COVID-19 emergence. The retention time during COVID-19 was significantly different from that of pre-COVID-19. Gender, type of first-used bDMARD, conventional synthetic DMARDs (csDMARDs) and corticoid usage status, disease activity levels were associated with retention time. ConclusionThe presence of COVID-19 has a significant effect on usage status of the biologic drug. Further longitudinal studies are needed to clarify the relationship between COVID-19 and drug usage as well as related factors.

Drug Retention Time of Immunosuppressive Therapy in Behcet’s Uveitis

ABSTRACT Purpose Behcet’s Disease is a chronic multisystem vasculitis associated with a blinding uveitis. Few comparative studies exist between conventional disease-modifying antirheumatic drugs (DMARDs) and biologic DMARDs in Behcet’s uveitis (BU). We therefore used drug retention time (DRT), an accepted surrogate measure of pharmacological efficacy and tolerability, to compare these treatments in patients with BU. Methods Retrospective chart review of patients who met the revised International Criteria for Behcet’s Disease (ICBD) treated at the Royal Victorian Eye and Ear Hospital, Australia, between 1985–2021. DRT was analysed with Kaplan-Meier plots and defined as total time on drug in the first medication-period for each DMARD in each patient. Results Forty-eight patients (37 males) with median age of 28.6 years were followed-up for a median of 8.0 years. At initial presentation, half had bilateral disease and median logMAR visual acuity was 0.176 (Snellen 6/9) in 62 uveitic eyes (16 anterior uveitis, 11 intermediate, 2 posterior, and 33 panuveitis). Thirty-three patients met ICBD initially. Prescribed corticosteroid-sparing agents were Cyclosporin (N = 24), Mycophenolate (N = 22), Azathioprine (N = 22), Methotrexate (N = 16), and Adalimumab (N = 15). Median DRT was 14.0, 27.4, 8.3, 24.0, and 52.0 months, respectively. DMARDs were discontinued 116 times and adverse effects (N = 37) were the main reason for cessation. Over time, patients were switched from Cyclosporin to Adalimumab earlier in the disease course due to poorer tolerance of adverse events. Conclusion Adalimumab’s drug retention time was found to be similar to and possibly better than cDMARDs in patients with BU, who often suffer from vision-threatening disease at first presentation.

Optimization of Pramipexole-Loaded In Situ Thermosensitive Intranasal Gel for Parkinson's Disease.

The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson's disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 32 full factorial design using Design-Expert® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X1) and HPMC K4M (X2) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X1 and 0.2% of X2 with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings.

Gastroprotective Chitosan Nanoparticles Loaded with Oleuropein: An In Vivo Proof of Concept.

Oleuropein is the main constituent of olive leaf extract, and it has shown antioxidant and gastroprotective properties against gastric ulcers. Chitosan nanoparticles are known for their mucoadhesive abilities, and consequently, they can increase the retention time of drugs in the gastrointestinal tract. Therefore, loading oleuropein onto chitosan nanoparticles is expected to enhance its biological efficiency. Oleuropein-loaded chitosan nanoparticles were prepared and characterized for particle size, surface charge, in vitro release, and anti-inflammatory activity. Their in vivo efficacy was assessed by measuring specific inflammatory and protective biomarkers, along with histopathological examination. The optimum oleuropein chitosan nanoparticles were cationic, had a size of 174.3 ± 2.4 nm and an entrapment efficiency of 92.81%, and released 70% of oleuropein within 8 h. They recorded a lower IC50 in comparison to oleuropein solutions for membrane stabilization of RBCs (22.6 vs. 25.6 µg/mL) and lipoxygenase inhibition (7.17 vs. 15.6 µg/mL). In an ethanol-induced gastric ulcer in vivo model, they decreased IL-1β, TNF-α, and TBARS levels by 2.1, 1.7, and 1.3 fold, respectively, in comparison to increments caused by exposure to ethanol. Moreover, they increased prostaglandin E2 and catalase enzyme levels by 2.4 and 3.8 fold, respectively. Immunohistochemical examination showed that oleuropein chitosan nanoparticles markedly lowered the expression of IL-6 and caspase-3 in gastric tissues in comparison to oleuropein solution. Overall, oleuropein chitosan nanoparticles showed superior gastroprotective effects to oleuropein solution since comparable effects were demonstrated at a 12-fold lower drug dose, delineating that chitosan nanoparticles indeed enhanced the potency of oleuropein as a gastroprotective agent.

An antifouling supramolecular polymer ophthalmic ointment alleviates symblepharon in rat alkali burn eyes.

Symblepharon is an adverse ocular disease resulting in ocular discomfort and impaired vision, severely dragging down a patient's quality of life. Due to the specificity of the ocular surface, the retention time of drugs on it is short, leading to limited therapeutic effects for ocular diseases. Therefore, it is imperative to design a novel drug delivery system, which can not only prolong the retention time of a drug but also play an anti-fibrosis role in symblepharon. Herein, an antifouling supramolecular polymer ophthalmic ointment consisting of poly(N-acryloyl alaninamide) (PNAAA), vitamin C (VitC) and levofloxacin (Levo) was developed (termed PNAVL ophthalmic ointment), which acted as a mucoadhesive and long-acting ocular delivery system. This antifouling PNAVL ophthalmic ointment improved the retention time of VitC and Levo, and simultaneously provided anti-inflammation and anti-fibrosis effects for mitigating symblepharon after ocular alkali burn injury.

Engineered assemblies from isomeric pentapeptides augment dry eye treatment

Changing positions of amino acid residues in the peptide sequence alters the peptide’ s assembly behaviors, affording various nanostructures. However, it remains elusive that how subtle changes in the peptide sequence influence the in vivo bioactivity of peptide-based nanocarriers, further impacting the efficacy of the encapsulated drugs. We report here a class of isomeric pentapeptide amphiphiles that associate into filaments with different dimensions, which were further used as carriers of Diquafosol tetrasodium (DQS), for the treatment of dry eye disease. Our results suggest that subtle changes in peptide sequences resulted in dramatically different molecular packings and distinct morphologies, which were verified by molecular dynamics simulations. In vivo results show that the drug retention time could be prolonged by the peptidic nanostructures on the ocular surface but were highly morphological-dependent. The longer retention time promised better therapeutic efficacy. In terms of facile synthesis and good biocompatibility, we believe that these peptides could be used for eye disease treatments or other related areas.

Formulation development and evaluation of nasal in situ gel of promethazine hydrochloride

Objective The present work aims to develop mucoadhesive thermosensitive nasal in situ gel for Promethazine hydrochloride using quality by design (QbD) approach. It can reduce nasal mucociliary clearance (MCC) and increase residence of the drug on nasal mucosa. This might increase drug absorption to improve bioavailability of the drug as compared to oral dosage form. Significance Promethazine hydrochloride is an antiemetic drug administered by oral, parenteral and rectal routes. These routes have poor patient compliance or low bioavailability. Nasal route is a better alternative as it has large surface area, high drug absorption rate and no first pass effect. Its only limitation is short drug retention time due to MCC. By formulating a mucoadhesive in situ gel, the MCC can be reduced, and drug absorption will be prolonged. Thus, improving bioavailability. Method In-situ gel was prepared by cold method having material attributes as concentration of Poloxamer 407 (X1) as gelling agent and hydroxypropyl methyl cellulose K4M (X2) as mucoadhesive agent. Critical Quality Attributes (CQA) were gelation temperature, mucoadhesive force and ex-vivo diffusion. Central composite design (CCD) was adopted for optimization. Result Optimized formulation satisfied all the CQA significant for nasal administration. Moreover, the formulation was found to be stable in accelerated stability studies for 3 months. Conclusion It can be concluded that since the drug can easily permeate through nasal mucosa and can gain access directly in the brain without undergoing first pass metabolism along with increased residence due to mucoadhesion, mucoadhesive in situ gel has potential to increase drug bioavailability.

Co-delivery of oxaliplatin prodrug liposomes with Bacillus Calmette-Guérin for chemo-immunotherapy of orthotopic bladder cancer

To reduce recurrence rate after transurethral resection of bladder tumor, long-term intravesical instillations of Bacillus Calmette-Guérin (BCG) and/or chemotherapeutic drugs is the standard treatment for non-muscle invasive bladder carcinoma. However, the main challenges of intravesical therapy, such as short retention time and poor permeability of drugs in the bladder, often require frequent and high-dose administrations, leading to significant adverse effects and financial burden for patients. Aiming at addressing these challenges, we developed a novel approach, in which the cell-penetrating peptide modified oxaliplatin prodrug liposomes and a low-dose BCG were co-delivered via a viscous chitosan solution (LRO-BCG/CS). LRO-BCG/CS addressed these challenges by significantly improving the retention capability and permeability of chemotherapy agents across the bladder wall. Then, oxaliplatin triggered the immunogenic cell death, and the combination of BCG simultaneously further activated the systemic anti-tumor immune response in the MB49 orthotopic bladder tumor model. As a result, LRO-BCG/CS demonstrated superior anti-tumor efficacy and prolonged the survival time of tumor-bearing mice significantly, even at relatively low doses of oxaliplatin and BCG. Importantly, this combinational chemo-immunotherapy showed negligible side effects, offering a promising and well-tolerated therapeutic strategy for bladder cancer patients.

Effectiveness and tolerability of antifibrotics in rheumatoid arthritis-associated interstitial lung disease

ObjectiveOur aim was to investigate the effectiveness and tolerability of antifibrotics in a real-world cohort of patients with rheumatoid arthritis-associated interstitial lung diseases (RA-ILD). MethodsIn this retrospective cohort study, we identified RA-ILD patients initiating antifibrotics at Mass General Brigham Integrated Health Care System, a large multi-hospital healthcare system in Boston, MA, USA. We used electronic query to identify all patients with at least 2 RA diagnosis codes and a prescription for either nintedanib or pirfenidone (2014–2023). All analyzed patients met 2010 American College of Rheumatology/European Alliance of Associations for Rheumatology classification criteria for RA and had definite RA-ILD according to Bongartz criteria. Data regarding pulmonary function test (PFT) results, adverse events (AEs), tolerability, and clinical data were collected. A linear mixed model with random intercept was used to compare the within-patient trajectory of the percent predicted forced vital capacity (FVCpp) within 18-months before to 18-months after antifibrotic initiation among those with these PFT data. Lung transplant-free survival and drug retention was estimated in a Kaplan-Meier analysis and a Cox regression analysis was performed to identify independent baseline factors associated with lung transplant or mortality. ResultsWe analyzed 74 patients with RA-ILD that initiated antifibrotics (mean age 67.8 years, 53 % male); 40 patients initiated nintedanib and 34 initiated pirfenidone. Median follow-up was 89 weeks (min 4, max 387). There was a significant improvement in the estimated slope of FVCpp after antifibrotic initiation (−0.3 % per year after initiation compared to −6.2 % per year before antifibrotic initiation, p = 0.03). Nintedanib and pirfenidone had similar FVCpp trajectory. Twenty-six patients (35 %) died and 4 (5 %) had undergone lung transplantation during follow-up. Male sex and heavy smoking were each associated with the composite outcome of lung transplant or mortality. AEs were reported in 41 (55 %) patients, with gastrointestinal (GI) AEs being most common (n = 30). The initial antifibrotic was discontinued in 34 (46 %) patients mostly due to GI AEs (n = 19). The median drug retention time was 142 weeks (95 %CI 56, 262) with no difference between nintedanib and pirfenidone (p = 0.68). ConclusionIn this first real-world study of antifibrotic use dedicated to RA-ILD, antifibrotic initiation was associated with a modestly improved trajectory of FVCpp. AEs were frequently reported, particularly GI, and discontinuation was common. However, lung transplant and mortality rates were still high, emphasizing the need for further therapeutic strategies in patients with severe RA-ILD. These real-world data complement previous trial data that investigated efficacy and safety.

Recent advances in porous nanomaterials‐based drug delivery systems for osteoarthritis

AbstractOsteoarthritis (OA) is a common degenerative disease that develops over time, characterized mainly by inflammatory joints, cartilage deterioration, and ultimately loss of normal joint function. Some of the limitations that restrict the effectiveness of current OA treatment procedures include minimal penetration of medications into cartilage and lack of vascularity, leading to insufficient bioavailability and systemic toxicity. To increase the effectiveness of treatment, it is necessary to create novel non‐invasive OA treatment techniques. Porous nanomaterials (PNMs) show great promise as sustained drug delivery systems (DDSs) due to their functionality, variable porosity, and high loading capacity. In addition, they can provide targeted drug delivery, facilitate controlled release of drugs, and prolong drug circulation and retention time while reducing adverse reactions and improving drug solubility. First, the current treatment methods and challenges are summarized. Subsequently, recent advances in DDSs for OA treatment based on PNMs with various pore sizes and structures are presented. Lastly, the parameters that affect the performance of DDSs are discussed by giving some suggestions for their design. The purpose of this review is to provide new insights into PNM‐based DDS design and to inspire readers to adopt the smart design of intra‐articular DDSs in the future.

Mucoadhesive and thermosensitive Bletilla striata polysaccharide/chitosan hydrogel loaded nanoparticles for rectal drug delivery in ulcerative colitis

Ulcerative colitis (UC) is a chronic disease with diffuse mucosal inflammation limited to the colon. A topical drug delivery system that could be facilely performed and efficiently retained at colon are attractive for clinical ulcerative colitis treatment. Herein, a novel platform for rectal administration of thermosensitive hydrogel co-loaded with nanoparticles to treat ulcerative colitis was developed. Thiolated-hyaluronic acid was synthesized, and prepared nanoparticles with zein and Puerarin. And the Bletilla striata polysaccharide with colonic mucosa repair effect was oxidized, and mixed with chitosan and β-sodium glycerophosphate to prepare thermosensitive hydrogel. Thermosensitive hydrogels were combined with nanoparticles to investigate their mucosal adhesion, retention, and permeability, as well as their therapeutic effects on ulcerative colitis. Thiolated-hyaluronic acid nanoparticles had good stability, and could be quickly converted into hydrogel at body temperature when combined with thermosensitive hydrogel. The nanoparticles-loaded thermosensitive hydrogel also was excellent at mucosal penetration, enhancing the retention time of drugs in colon, and effectively controlling drug release. In vivo ulcerative colitis treatment revealed that the nanoparticles-loaded hydrogel significantly repaired the colonic mucosa and inhibit colonic inflammation. Therefore, the thermosensitive hydrogel co-loaded nanoparticles will have a promising application in effective treatment of ulcerative colitis by topical administration.

Aflibercept Loaded Eye-Drop Hydrogel Mediated with Cell-Penetrating Peptide for Corneal Neovascularization Treatment.

Corneal neovascularization (CoNV) is a major cause of visual impairment worldwide. Currently, available treatment options have limited efficacy and are associated with adverse effects due to biological barriers and clearance mechanisms. To address this challenge, a novel topical delivery system is developed-Gel 2_1&Eylea-an aflibercept-loaded eye-drop hydrogel mediated with cell-penetrating peptide 1. Gel 2_1&Eylea demonstrates superior membrane permeability, increased stability, and prolonged drug retention time on the ocular surface, and thus may improve drug efficacy. In a rabbit CoNV model, Gel 2_1&Eylea significantly reduces the density of neovascularization with no adverse effects on normal corneoscleral limbal vessels, demonstrating high efficacy and biocompatibility. This work identifies a promising treatment for CoNV which has the potential to benefit other ocular neovascular diseases.

Active Transport and Ocular Distribution of Intravitreally Injected Liposomes.

Drug delivery to the retina remains a challenge due to ocular barriers and fast clearing mechanisms. Nanocarrier drug delivery systems (NDDSs) hold the promise of prolonging intraocular retention times and increasing drug concentrations in the retina. Anionic and cationic PEGylated liposomes, loaded with oxaliplatin (OxPt) to be used as trace element, were prepared from dry lipid powders. The differently charged liposomes were intravitreally injected in C57BL/6JrJ mice; eyes were harvested 2hours and 24hours post-injection. To investigate active transport mechanisms in the eye, a subset of mice were pre-injected with chloroquine before injection with cationic liposomes. Eyes were dissected and the distribution of OxPt in different tissues were quantified by inductively coupled plasma mass spectrometry (ICP-MS). Both liposome formulations enhanced the retention time of OxPt in the vitreous over free OxPt. Surprisingly, when formulated in cationic liposomes, OxPt translocated through the retina and accumulated in the RPE-sclera. Pre-injection with chloroquine inhibited the transport of liposomal OxPt from the vitreous to the RPE-sclera. We show that liposomes can enhance the retention time of small molecular drugs in the vitreous and that active transport mechanisms are involved in the trans retinal transport of NDDS after intravitreal injections. These results highlight the need for understanding the dynamics of ocular transport mechanisms in living eyes when designing NDDS with the back of the eye as the target. Active transport of nanocarriers through the retina will limit the drug concentration in the neuronal retina but might be exploited for targeting the RPE.

Non‐Newtonian blood flow with magnetic nanoparticles in a W‐shaped stenosed arterial segment: A numerical study

AbstractFlow of blood, infused with magnetic nanoparticles, in a W‐shaped stenosed human arterial segment is studied numerically using a realistic non‐Newtonian blood rheology model. It is observed that the Newtonian model predicts less time to reach a steady state than the non‐Newtonian blood rheology model. An increased drug retention time at the target site with an increase in nanoparticle concentration is predicted. Detailed simulations further reveal that the skin friction coefficient does not increase significantly with the increase in nanoparticle concentration. Hence, it is anticipated from our study that the infusion of drug‐carrying nanoparticles in blood flow does not excessively enhance wall shear stress that may lead to arterial wall damage. An overall increase in heat transfer rates and wall shear stress at the stenosed section is seen with an increase in Reynolds number. The present study provides valuable information for designing computer‐assisted drug delivery systems.

Intranasal nanotherapeutics for brain targeting and clinical studies in Parkinson's disease.

Parkinson's disease (PD) is the second leading neurodegenerative disease globally, impacting the quality of life of a large population. Millions of people are affected by PD, and it is estimated that the treatment cost of PD in the USA can rise to 79 billion dollars by 2037. Limited drugs are approved by USFDA, which only provides systematic relief. Further, the drug efficacy is challenged due to low drug-brain concentration due to first-pass metabolism and blood-brain barrier (BBB). Intranasal drug administration can offer several advantages over systemic administration for efficient brain delivery. Nose-to-brain (N2B) drug delivery can enhance brain bioavailability, reduce enzymatic degradation, and reduce systemic adverse effects. However, due to poor absorption from the nasal mucosa, intranasal administration can be challenging for hydrophilic drugs. The drug mucociliary clearance, retention time, and nasal enzymatic degradation can also affect N2B drug delivery. Nanocarriers can enhance residence time, improve nasal permeation, increase brain uptake, and reduce enzymatic degradation. This review discusses the roles and applications of various N2B nanocarriers to treat PD effectively and clinical trials of antiparkinson molecules. Lastly, safety aspects and prospects of potential nanotherapeutics for the effective treatment of PD are discussed.

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

Super‐stable homogeneous embolic agents advance the treatment of hepatocellular carcinoma

Development and physicochemical characterization of solid lipid nanoparticles containing tinidazole

Background: Periodontitis is a chronic inflammation of the periodontal tissues. To increase the effectiveness of treatment, antibiotics selected should have a spectrum of action on bacteria causing periodontitis, while also meeting the requirements of cell penetration and prolonging of the retention time at the target site. Therefore, this study aimed at developing solid lipid nanoparticles (SLNs) containing tinidazole (TNZ-SLNs) oriented to be incorporated into the gel to increase the penetration ability and prolong drug retention time in periodontal tissues. Objectives: Therefore, this study aimed to develop and characterize solid lipid nanoparticles (SLNs) containing tinidazole (TNZ-SLNs) oriented to be incorporated into the gel to increase the penetration ability and prolong drug retention time in periodontal tissues. Methods: TNZ-SLNs were prepared by combining hot homogenization and solvent evaporation using different types of lipids and surfactants. Factors related to the formula and the preparation process were investigated, Design Expert 12.0, FormRules v2.0 and InForm v3.1 software were used to design experiments and optimize the formula. The prepared nanoparticles were characterized by particle size, polydispersity index (PDI), encapsulation efficiency (EE), etc. Results: The optimized formulation had a particle size of 197.60 ± 19.67 nm, a PDI of 0.247 ± 0.011, a zeta potential of -15.79 ± 0.75mV and an EE of 37.96 ± 0.91%. TNZ-SLNs showed prolonged in vitro drug release (for up to 24 hours), while TNZ material achieved about 100% drug release after 4 hours. Conclusion: TNZ-SLNs were successfully fabricated and physicochemically characterized. Key words: Tinidazole, solid lipid nanoparticles, periodontitis.

ОЦЕНКА БИОФАРМАЦЕВТИЧЕСКИХ ПОКАЗАТЕЛЕЙ НОВОГО ИНТРАНАЗАЛЬНОГО ПРОТИВОВИРУСНОГО ПРЕПАРАТА НА ОСНОВЕ IN SITU СИСТЕМЫ

Intranasal antiviral administration is a modern method for delivery of both immunobiological and synthetic substances. This route in medication delivery has a number of advantages: it is non-ivasive, highly practical, bioavailable and provides protective immunity at the entry gates of respiratory infections. The problem of intranasal delivery systems is short drug retention time under the effect of mucociliary clearance that results into limited absorbtion and prolongation capability. Аnatomical structure of the nasal cavity as well as the effect of mucociliary clearance result into an early evacuation of the administered drug so the active substance is not fully delivered. The solution to the problem is the usage of in situ delivery systems with stimulus typical for nasal cavity applied: temperature, ionic composition, pH. These systems make a phase transition at the area of application with viscosity increase enough for continuous effect on the mucous membrane. Earlier an intrasal ribavirin delivery system has been designed at the Institute of Pharmacy named after A. Nelubin. Ribavirin is an active substance known for more than forty years, approved by the FDA and included in the clinical guidelines for the treatment of diseases caused by SARS-CoV-2. The purpose of that research was to define the main biopharmaceutical parameters of the designed composition. The delivery system included ribavirin (10 mg/ml), poloxamer 407 – 16%, chitosan formate – 4%. The evaluation of biopharmaceutical characteristics was carried out according to the parameters рН, phase transition temperature, gelation time, viscosity, mucoadhesion and also spray torches, distribution area and retention on an in vitro model, releasing in the Franz cell test. Results of the evaluation of indicators: pH of the system – 7,07±0,12; sol-gel transition end temperature 30,7±0,4℃; gelation time - 36±15 s; increase in viscosity after phase transition - 7 times; mucoadhesion - 8,6±1,5 Н; distribution area - 44,9±5,3 cm2; retention on an in vitro model - 85,0±3,5%. During the determination of the release of ribavirin, it was shown that in the first 5 minutes about 62.5% is released, then the release is gradual and by six hours it reaches 84.7%. Based on the obtained data, it can be concluded that the developed composition is potentially promising and that it can be further evaluated in preclinical studies.

Targeted delivery of temozolomide by nanocarriers based on folic acid-hollow TiO2 -nanospheres for the treatment of glioblastoma

Glioblastoma multiforme (GBM) is a highly malignant brain tumor. Its standard treatment includes a combination of surgery, radiation, and chemotherapy. The last involves the oral delivery of free drug molecules to GBM such as Temozolomide (TMZ). However, this treatment has limited effectiveness owing to the drugs premature degradation, lack of cell selectivity, and poor control of pharmacokinetics. In this work, the development of a nanocarrier based on hollow titanium dioxide (HT) nanospheres functionalized with folic acid (HT-FA) for the targeted delivery of temozolomide (HT-TMZ-FA) is reported. This approach has the potential benefits of prolonging TMZ degradation, targeting GBM cells, and increasing TMZ circulation time. The HT surface properties were studied, and the nanocarrier surface was functionalized with folic acid as a potential targeting agent against GBM. The loading capacity, protection from degradation, and drug retention time were investigated. Cell viability was performed to assess the cytotoxicity of HT against LN18, U87, U251, and M059K GBM cell lines. The cell internalization of HT configurations (HT, HT-FA, HT-TMZ-FA) was evaluated to study targeting capabilities against GBM cancer. Results show that HT nanocarriers have a high loading capacity, retain and protect TMZ for at least 48 h. Folic acid-functionalized HT nanocarriers successfully delivered and internalized TMZ to glioblastoma cancer cells with high cytotoxicity through autophagic and apoptotic cellular mechanisms. Thus, HT-FA nanocarriers could be a promising targeted delivery platform for chemotherapeutic drugs for the treatment of GBM cancer.

Evaluation of Khaya gum (Khaya senegalensis) as a polymer in the formulation of floating in situ gels of metoprolol succinate

Metoprolol succinate, a β-selectiveadrenergic blocker, has a short half-life, low bioavailability, and high dosingfrequency. In-situ gel drug delivery is a good approach to achieve sustained release for once-daily administration thatwill prolong drugretention time at the stomach and increase absorption. Thus,the aim of the study is to formulate floatingin-situ gel formulations of metoprolol succinate using Khaya gum (Khayasenegalensis, family Meliaceae) as a polymer. Khaya gum wascharacterized and used in formulating in situ gels of metoprololsuccinate in comparison with Hydroxyl Propyl Methyl Cellulose (HPMC K15M) andXanthan gum. The in-situ gel formulations were characterized forappearance, swelling, in- vitro buoyancy and in-vitro drugrelease. FTIR revealed major peaks characteristic of the gum. Khaya gum showedhigh swelling and good flow properties. In-situ gel formulations of metoprolol succinatecontaining Khaya were light brown with near neutral pH, higher swelling and a total floating time &amp;gt;24 h,comparable to those containing HPMC and Xanthan gums. Dissolution time t80was 60.50 to &amp;gt;240 min with ranking Khaya&amp;nbsp;&amp;lt;HPMC&amp;nbsp;&amp;lt;Xanthan. Khaya gum providesa cheaper, suitable polymer for formulating floating in-situ gels with prolonged buoyancy and drug release.