The fabrication and development of nanomaterials for the treatment of prostate cancer have gained significant appraisal in recent years. Advancements in synthesis of organic and inorganic nanomaterials with charge, particle size, specified geometry, ligand attachment etc have resulted in greater biocompatibility and active targeting at cancer site. Despite all of the advances made over the years in discovering drugs, methods, and new biomarkers for cancer of the prostate (PCa), PCa remains one of the most troubling cancers among people. Early on, effective diagnosis is an essential part of treating prostate cancer. Prostate-specific antigen (PSA) or serum prostate-specific antigen is the best serum marker widely accessible for diagnosis of PCa. Numerous efforts have been made over the past decade to design new biosensor-based strategies for biomolecules detection and PSA miniaturization biomarkers. The growing nanotechnology is expected to have a significant effect in the immediate future on scientific research and healthcare. Nanotechnology is thus predicted to find a way to solve one of the most and long-standing problem, "early cancer detection". For early diagnosis of PCa biomarkers, different nanoparticles with different approaches have been used. In this review, we provide a brief description of the latest achievements and advances in the use of nanoparticles for PCa biomarker diagnosis.

https://www.mdpi.com/2079-4991/10/9/1696/pdf

Nanotreatment and Nanodiagnosis of Prostate Cancer: Recent Updates.

A large number of hydrophilic and hydrophobic carriers in pharmaceutical excipients are available today which are used for formulation of solid dispersions. Depending on nature of carriers the immediate release solid dispersions and/or controlled release solid dispersions can be formulated. Initially crystalline carriers were used which are transformed into amorphous solid dispersions with enhanced properties. The carriers used previously were mostly synthetic one. Recent trend towards the use of natural carriers have replaced the use of synthetic carriers. This review is the overview of various synthetic, natural, semisynthetic, modified natural hydrophilic carriers used for formulation of solid dispersions.

https://apb.tbzmed.ac.ir/PDF/apb-10-359.pdf

A Review on Solid Dispersion and Carriers Used Therein for Solubility Enhancement of Poorly Water Soluble Drugs.

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Nanocrystals as a master key to deliver hydrophobic drugs via multiple administration routes.

Antiretroviral (ARV) drugs have, for many years, been studied and administered in the prevention and treatment of human immunodeficiency virus (HIV). Intramuscular (IM) injection of long acting (LA) ARVs are in clinical development, but injectable formulations require regular access to healthcare facilities and disposal facilities for sharps. The development of a discrete, self-administered, and self-disabling vehicle to deliver ARVs could obviate these issues. This study describes the formulation, mechanical characterization, and in vivo evaluation of dissolving microarray patches (MAPs) containing a LA nanosuspension of the ARV, rilpivirine (RPV, RPV LA), for vaginal delivery. This is the first study to apply MAPs into vaginal tissue. The RPV LA MAPs penetrate ex vivo skin and a synthetic vaginal skin model and withstand the effects of potential dragging motion across synthetic vaginal epithelium. In in vivo studies, the mean plasma concentration of RPV in rats at the 56 day endpoint (116.5 ng mL-1 ) is comparable to that achieved in the IM control cohort (118.9 ng mL-1 ). RPV is detected systemically, in lymph and vaginal tissue, indicating the potential to deliver RPV LA to primary sites of viral challenge and replication. This innovative research has future potential for patients and healthcare workers, particularly in low-resource settings.

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Design, Formulation, and Evaluation of Novel Dissolving Microarray Patches Containing Rilpivirine for Intravaginal Delivery

Curcumin (CUR), a hydrophobic polyphenolic compound derived from the rhizome of the herb Curcuma longa, has shown a wide range of biological applications including cancer prevention and treatment. However, low water solubility, poor pharmacokinetics and suboptimal tumor uptake, greatly hamper its anti-cancer efficacy. This study was designed to develop a novel s-cyclodextrin-curcumin (CD-CUR) self-assembly approach for sustained release and improved curcumin delivery in prostate cancer cells. Cyclodextrin-curcumin self-assemblies were prepared by solvent evaporation technique. The formation of self-assemblies was evaluated by Fourier Transform Infra-red (FTIR), Differential Scanning Calorimetry (DSC), Thermo-gravimetric Analysis (TGA), Scanning and Transmission Electron Microscopic (SEM/TEM) analyses. Intracellular uptake of these self-assemblies was evaluated by Flow cytometry and immunofluorescence microscopy analyses. Therapeutic efficacy of these self-assemblies was determined by cell proliferation and colony formation assays using C4-2, DU145, LNCaP and PC3 prostate cancer cells. The effect of CD-CUR formulation on apoptosis related proteins was determined by immunoblotting. Physico-chemical characterization analyses confirm the formation of CD-CUR self-assemblies, which demonstrated excellent stability and solubility in physiological solutions and showed enhanced intracellular uptake in cells. Additionally, CD-CUR formulation has exhibited an improved therapeutic efficacy and enhanced PARP cleavage in prostate cancer cells compared to free curcumin. In conclusion, CD-CUR self-assemblies enhance intracellular delivery of active curcumin in prostate cancer cells and improved its therapeutic efficacy. This study suggests that CD-CUR self-assembly may be a useful nanoscale formulation for improved curcumin delivery in prostate cancer cells. Tumor specific antibody targeted CD-CUR formulation can further improve the in vivo delivery of curcumin in prostate tumors. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-425.

Abstract LB-425: Design of ß-cyclodextrin-curcumin self-assembly: A new approach for enhanced curcumin delivery and therapeutic efficacy in prostate cancer cells

Background Ivermectin is an FDA-approved broad-spectrum anti-parasitic agent that has been shown to inhibit SARS-CoV-2 replication in vitro. Objective We aimed to assess the therapeutic efficacy of ivermectin mucoadhesive nanosuspension intranasal spray in treatment of patients with mild COVID-19. Methods This clinical trial included 114 patients diagnosed as mild COVID-19. Patients were divided randomly into two age and sex-matched groups; group A comprising 57 patients received ivermectin nanosuspension nasal spray twice daily plus the Egyptian protocol of treatment for mild COVID-19 and group B comprising 57 patients received the Egyptian protocol for mild COVID-19 only. Evaluation of the patients was performed depending on improvement of presenting manifestations, negativity of two consecutive pharyngeal swabs for the COVID-19 nucleic acid via rRT-PCR and assessments of hematological and biochemical parameters in the form of complete blood counts, C-reactive protein, serum ferritin and d-dimer which were performed at presentation and 7 days later. Results Of the included patients confirmed with mild COVID-19, 82 were males (71.9%) and 32 females (28.1%) with mean age 45.1 ± 18.9. In group A, 54 patients (94.7%) achieved 2 consecutive negative PCR nasopharyngeal swabs in comparison to 43 patients (75.4%) in group B with P = 0.004. The durations of fever, cough, dyspnea and anosmia were significantly shorter in group A than group B, without significant difference regarding the duration of gastrointestinal symptoms. Duration taken for nasopharyngeal swab to be negative was significantly shorter in group A than in group B (8.3± 2.8 days versus 12.9 ± 4.3 days; P = 0.0001). Conclusion Local use of ivermectin mucoadhesive nanosuspension nasal spray is safe and effective in treatment of patients with mild COVID-19 with rapid viral clearance and shortening the anosmia duration. Clinicaltrialsgov identifier NCT04716569; https://clinicaltrials.gov/ct2/show/NCT04716569.

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Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19.

Objective: To develop mucoadhesive tablets for the vaginal delivery of progesterone (P4) to overcome its low oral bioavailability resulting from drug hydrophobicity and extensive hepatic metabolism.Methods: The tablets were prepared using mixtures of P4/Pluronic® F-127 solid dispersion and different mucoadhesive polymers. The tablets physical properties, swelling index, mucoadhesion and drug release kinetics were evaluated. P4 pharmacokinetic and pharmacodynamic properties were evaluated in female rabbits and compared with vaginal micronized P4 tablets and intramuscular (IM) P4 injection, respectively.Results: The tablets had satisfactory physical properties and their swelling, in vitro mucoadhesion force and ex vivo mucoadhesion time were dependent on tablet composition. Highest swelling index and mucoadhesion time were detected for tablets containing 20% chitosan-10% alginate mixture. Most tablets exhibited burst release (∼25%) during the first 2 h but sustained the drug release for ∼48 h. In vi...

Mucoadhesive tablets for the vaginal delivery of progesterone: in vitro evaluation and pharmacokinetics/pharmacodynamics in female rabbits.

Curcumin (CUR) is one of the most commonly used herbal product; it shows effective anti-inflammatory and anti-oxidant effects. However, poor aqueous solubility and low permeability are the major challenges in therapeutic application of curcumin. One class of vesicular nanocarriers called “Niosome and ethosome” which have proved to possess distinct advantages were used to encapsulate curcumin and evaluated for their morphology, particle size, zeta potential, entrapment efficiency (EE%) and drug release. They were incorporated into hydroxy propyl methyl cellulose (HPMC15000) gel then, evaluated on the rat skin via inhibition of carrageenan induced rat paw edema. The results showed that the particle size of curcumin loaded niosomes and ethosomes were ranged (317.5±1.91 to 558.3±8.587 nm) and (182.1±5.3 to 354.5±30.03 nm), respectively. Skin permeation studies demonstrated that CUR permeability coefficient through rat kin for gel formulations of loaded vesicles was ~ four times higher as compared to free CUR. The in-vivo anti-inflammatory studies proved that gel formulations of CUR vesicles possessed higher significant inhibition of carrageenan induced rat paw edema when compared to pure curcumin. Accordingly, the results revealed that, curcumin loaded nanovesicels held great potential approaches as anti-inflammatory in topical application.

https://bpsa.journals.ekb.eg/article_93599_8a6ba1949a9b7305069e6e771cb345db.pdf

Performance of curcumin in nanosized carriers niosomes and ethosomes as potential anti-inflammatory delivery system for topical application

Background Progesterone (PG), a natural female sex hormone is used clinically in menopausal hormone replacement therapy and to control reproductive functions. Its very limited aqueous solubility results in reduced oral bioavailability and low patient compliance when administered in high doses. The aim of this study was to enhance PG aqueous solubility and vaginal delivery using solid dispersion, inclusion complex and micellar solubilization techniques. Methods PG solid dispersions and inclusion complexes were prepared by solvent evaporation method using different polymers, such as cyclodextrins, polyvinyl pyrrolidone (PVP), poly (ethylene glycol) 6000, Pluronic® F-127 and Pluronic® F-68. PG was also incorporated into polymeric micelles of Pluronic® F-127, Pluronic® F- 68, Brij®35 and Myrj®52. The prepared solid dispersions, inclusion complexes and micelles were characterized using different techniques. Drug permeability across rabbit vaginal mucosa was also studied. Results Dissolution studies of PG solid dispersions showed that the highest drug dissolution rate was achieved at PG/polymer weight ratio of 5:5. Further, complete drug dissolution was obtained for PG/Pluronic® F-127 solid dispersion after 15 min compared to 42% dissolution for the drug alone. Brij®35 micelles had a drug loading capacity ~15%, which increased the drug aqueous solubility by more than 20 folds. PG permeability coefficients through rabbit vaginal mucosa for PG/Brij®35 micelles and PG/Pluronic® F-127 micelles were ~ two times higher than that of the drug alone. Conclusion These results confirm that Brij®35 and Pluronic® F-127 micelles are promising carriers to overcome PG shortcomings through enhancing its aqueous solubility and vaginal permeability.

Solubilization and Enhancement of Ex Vivo Vaginal Delivery of Progesterone Using Solid Dispersions, Inclusion Complexes and Micellar Solubilization

Purpose Anosmia or hyposmia, with or without taste changes, are common symptoms that occur in SARS-CoV-2 infection and frequently persist as post-COVID-19 manifestations. This is the first trial to assess the potential value of using local ivermectin in the form of a mucoadhesive nanosuspension nasal spray to treat post-COVID-19 anosmia. Methods It is a controlled, randomized trial. Participants were recruited from South Valley University Hospitals in Qena, Upper Egypt, from the ENT and Chest Diseases Departments and outpatient clinics. Patients with persistent post COVID-19 anosmia were randomly divided into two groups, the first group “ivermectin group” included 49 patients treated by ivermectin nanosuspension mucoadhesive nasal spray (two puffs per day). The second group included 47 patients “placebo group” who received saline nasal spray. Follow- up of anosmia [using Visual analogue scale (VAS)] in all patients for three months or appearance of any drug related side effects was done. Results The mean duration of pre-treatment post COVID-19 anosmia was 19.5± 5.8 days in the ivermectin group and 19.1± 5.9 days in the placebo group,p˃0.05. Regarding the median duration of anosmia recovery, the ivermectin group recovered from post COVID-19 anosmia in 13 days compared to 50 days in the placebo group, p˂ 0.001. Following the first week of ivermectin nanosuspension mucoadhesive nasal spray therapy, the ivermectin group had a significantly higher percentage of anosmia recovery (59.2%) than the placebo group (27.7%), p˂ 0.01, with no significant differences in recovery rates between the two groups at 1, 2, and 3 months of follow up, p˃0.05. Conclusion In the small number of patients treated, local Ivermectin exhibited no side effects. In persistent post-COVID-19 anosmia, it could be used for one week at the most as the treatment was extended to one, two and three months, with no difference in recovery compared to the placebo treatment. Trial Registration No NCT04951362.

https://www.dovepress.com/getfile.php?fileID=84044

Abeer S. Hassan

Papers

Clinical, Biochemical and Molecular Evaluations of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Reducing Upper Respiratory Symptoms of Mild COVID-19.

Mucoadhesive tablets for the vaginal delivery of progesterone: in vitro evaluation and pharmacokinetics/pharmacodynamics in female rabbits.

Performance of curcumin in nanosized carriers niosomes and ethosomes as potential anti-inflammatory delivery system for topical application

Solubilization and Enhancement of Ex Vivo Vaginal Delivery of Progesterone Using Solid Dispersions, Inclusion Complexes and Micellar Solubilization

Possible Role of Ivermectin Mucoadhesive Nanosuspension Nasal Spray in Recovery of Post-COVID-19 Anosmia