Preparation and evaluation of vaginal suppo-sponges loaded with benzydamine, in-vitro/in-vivo study.

This study aimed to design a new Benzydamine HCl (BNZ) suppo-sponge for controlled, mucoadhesive dosage form for vaginal candidiasis treatment, offering advantages over traditional creams, ointments, or gels. BNZ-loaded suppo-sponges were fabricated by simple casting / freeze-drying technique utilizing the cross-linking of chitosan (Cs) with vanillin (V). Vaginal suppo-sponges were prepared based on different vanillin cross-linking ratios (V).n), from 0 to 2%w/w. To best of our knowledge, this is the first study that uses Schiff's base between chitosan and vanillin as a drug delivery system to treat fungal vaginal infections. Schiff's base formation was confirmed by FT-IR. In-vitro appraisal showed acceptable physical and mechanical characteristics. Formulations based on cross-linking of Cs with V showed a more pronounced in-vitro antifungal activity. In-vitro drug release revealed a prolonged release pattern, becoming more noticeable with the higher cross-linked suppo-sponges (22.34% after 8 h). In-vivo testing of CsV2 suppo-sponge indicated a more pronounced reduction in fungal count than both CsV0 and Tantum® Rosa in the first week, with a peak reduction on day 7 and the 10th and 11th days of the second week. Conclusively, Chitosan/vanillin suppo-sponges represent a promising delivery system for drugs intended for local treatment of vaginal candidiasis. than both CsV0 and Tantum® Rosa in the first week, with a peak reduction on day 7 and the 10th and 11th days of the second week. Conclusively, Chitosan/vanillin suppo-sponges represent a promising delivery system for drugs intended for local treatment of vaginal candidiasis.

Propolis-loaded nanostructured lipid carriers halt breast cancer progression through miRNA-223 related pathways: an in-vitro/in-vivo experiment.

The most frequent malignant tumor in women is breast cancer, and its incidence has been rising every year. Propolis has been used for its antibacterial, antifungal, and anti-inflammatory properties. The present study aimed to examine the effect of the Egyptian Propolis Extract (ProE) and its improved targeting using nanostructured lipid carriers (ProE-NLC) in Ehrlich Ascites Carcinoma (EAC) bearing mice, the common animal model for mammary tumors. EAC mice were treated either with 5-fluorouracil (5-FU), ProE, ProE-NLC, or a combination of ProE-NLC and 5-FU. Their effect on different inflammatory, angiogenic, proliferation and apoptotic markers, as well as miR-223, was examined. ProE and ProE-NLC have shown potential anti-breast cancer activity through multiple interrelated mechanisms including, the elevation of antioxidant levels, suppression of angiogenesis, inflammatory and mTOR pathways, and induction of the apoptotic pathway. All of which is a function of increased miRNA-223 expression. The efficiency of propolis was enhanced when loaded in nanostructured lipid carriers, increasing the effectiveness of the chemotherapeutic agent 5-FU. In conclusion, this study is the first to develop propolis-loaded NLC for breast cancer targeting and to recommend propolis as an antitumor agent against breast cancer or as an adjuvant treatment with chemotherapeutic agents to enhance their antitumor activity and decrease their side effects. Tumor targeting by ProE-NLC should be considered as a future therapeutic perspective in breast cancer.

Pentoxifylline/Valsartan co-delivery in liposomal gel alters the inflammatory HMGB-1/ TLR pathway and promotes faster healing in burn wounds: A promising repurposed approach.

Burn wounds are one of the most severe complex forms of trauma. Hence, new treatment strategies that facilitate the healing process; reduce the severity and the healing time is the main concern of the health care systems. In this work, pentoxifylline-valsartan, (PTX- VAL), loaded liposomes integrated into gel were designed for the first time as a novel co-delivery carrier for the treatment of burn wounds. The objective of this work was to investigate the ability of the nano-based liposomal system to co-entrap two repurposed drugs; hydrophilic pentoxifylline and lipophilic valsartan for topical treatment of burn wounds. The impact of increasing the phospholipid amount to enhance the co-entrapment of PTX and VAL was investigated and in-vitro evaluation of the prepared formulations was conducted to choose the optimum composition with the highest entrapment of both drugs adopting a simple, reliable derivative spectrophotometric method. Structure elucidation was also performed using a transmission electron microscope. In addition, A simple selected derivative spectrophotometric method was developed for the assay of PTX-VAL novel combination. The proven selectivity, precision and accuracy assured the reliability of this analytical method. Being economic and fast makes routine application of the developed analytical method is recommended in pharmaceutical industry. The selected liposomal formulation integrated into gel matrix (PTX-VAL-LG) showed; nanometric size, acceptable entrapment efficiency of both PTX and VAL as well as sustained release profiles and thus, enhanced action.

Pegylated liquisomes: A novel combined passive targeting nanoplatform of L-carnosine for breast cancer.

PEGylated Liquisomes (P-Liquisomes), a novel drug delivery system was designed for the first time by incorporating phospholipid complex in PEGylated liquid crystalline nanoparticles (P-LCNPs). L-carnosine (CN), a challenging dipeptide, has proven to be a promising anti-cancer drug. However, it exhibits high water solubility and extensive in-vivo degradation that halts its use. The objective of this work was to investigate the ability of our novel system to improve the CN anticancer activity by prolonging it's release and protecting it in-vivo. In-vitro appraisal revealed spherical light-colored vesicles encapsulated in the liquid crystals, confirming the successful formation of the combined system. P-Liquisomes were nano-sized (149.3 ± 1.4 nm), with high ZP (-40.2 ± 1.5 mV), complexation efficiency (97.5 ± 0.9%) and outstanding sustained release of only 75.4% released after 24 h, compared to P-LCNPs and Phytosomes. The results obtained with P-Liquisomes are considered as a break through compared to P-LCNPs or Phytosomes alone, especially when dealing with the hydrophilic CN. In-vitro cytotoxicity evaluation, revealed superior cytotoxic effect of P-Liquisomes (IC50 = 25.9) after 24 h incubation. Besides, P-Liquisomes proved to be non-toxic in-vivo and succeeded to show superior chemopreventive activity manifested by reduction of; % tumor growth (7.1%), VEGF levels (14.3 pg/g tissue), cyclin D1 levels 15.5 ng/g tissue and elevation in caspase-3 level (36.4 ng/g tissue), compared to Phytosomes and CN solution. Conclusively, P-Liquisomes succeded to achieve the maximum therapeutic outcome of CN without altering its activity and might be used as a sustained delivery system for other promising hydrophilic compounds.

Valsartan solid lipid nanoparticles integrated hydrogel: A challenging repurposed use in the treatment of diabetic foot ulcer, in-vitro/in-vivo experimental study.

The article presents an experimental study on the possible repurposed use of valsartan (Val), in the local treatment of uncontrolled diabetic foot ulcer. Solid lipid nanoparticles (SLN), loaded with Val were prepared by applying 32 full factorial design using modified high shear homogenization method. The lipid phase composed of Precirol® ATO 5 (P ATO 5) and/or Gelucire 50/13 (G 50/13) in different ratios and a nonionic emulsifier, Pluronic 188 (P188), was used in different percentages. Optimized formulation was further integrated in hydroxyl propyl methyl cellulose (HPMC) gel for the ease of administration. In-vitro and in-vivo characterizations were investigated. The prepared nanoparticles showed small particle size, high entrapment efficiency and sustained drug release. Microbiologically, Val-SLN showed a prominent decrease in the biofilm mass formation for both gram-positive and gram-negative bacteria, as well as a comparable minimum inhibitory concentration level to levofloxacin alone. Diabetes was induced in 32 neonatal Sprague-Dawley rats. At 8 weeks of age, rats with blood sugar level >160 were subjected to surgically induced ulcer. Treatment with Val-SLN for 12 days revealed enhanced healing characteristics through cyclooxygenase-2 (COX-2), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), nitric oxide (NO), transforming growth factor-beta (TGF-ß), matrix metalloproteinase (MMPs) and vascular endothelial growth factor (VEGF) pathways. Histological examination revealed re-epithelization in Val-SLN treated ulcer, as well as decrease in collagen using trichrome histomorphometric analysis.

Evaluation of chamomile oil and nanoemulgels as a promising treatment option for atopic dermatitis induced in rats.

Background: Atopic dermatitis is a chronic inflammatory skin disease that remarkably affects the quality-of-life of patients. Chamomile oil is used to treat skin inflammations. We evaluated the efficacy of chamomile oil and nanoemulgel formulations as a natural alternative therapeutic option for atopic dermatitis.Research design and methods: Formulations were developed comprising chamomile oil: olive oil (1:1), Tween 20/80 or Gelucire 44/14 as surfactant-cosurfactant mixtures, propylene glycol (10%w/w), water and hydroxypropyl methylcellulose (3%w/w). In-vitro physicochemical characterization, stability testing and in-vivo assessment of inflammatory biomarkers and histopathological examination of skin lesions were conducted in rats induced with atopic dermatitis.Results: Nanoemulgels G1 and X1 which displayed the smallest particle size of 137.5 ± 2.04 and 207.1 ± 5.44 nm, good homogeneity and high zeta-potential values of -26.4 and -32.7 mV were selected as the optimized emulgel. Nanoemulgels were nonirritating of pH value 5.56, readily spreadable, and were physically stable following 10 heating-cooling cycles. Treatment with nanoemulgels showed a two-fold decrease in duration of skin healing and no spongiosis compared to chamomile oil. Levels of biomarkers were reduced after topical application of both nanoemulgels and chamomile oil.Conclusion: Nanoemulgels are a potential cost effective, safe topical carrier system for chamomile in treating atopic dermatitis.

Controlled release Ibu-cryobarriers for the prevention of post-operative adhesions: In-vitro/in-vivo comparative study.

Post-operative adhesion is a common cause of several complications including intestinal obstruction, chronic pelvic pain and/or infertility. Adhesions are fibrous bands that result from the inflammatory reactions due to peritoneum damage. The current study focused on designing an effective anti-inflammatory loaded barrier for the prevention of post-operative adhesions. The proposed method is based on the use of polyvinyl alcohol (PVA), cryobarrier loaded with Ibuprofen (Ibu). Anti-adhesive Ibu-cryobarriers were prepared in different forms, and subjected to in-vitro evaluation comprising; drug release rate, maximum swelling index, morphological examination using scanning electron microscope (SEM), fourier-transform infrared spectroscopy (FTIR) and mechanical properties. Optimized cryobarriers were further investigated for their in-vivo effectiveness in preventing post-operative adhesions in female Sprague-Dawley rats. All formulations showed appropriate physical and morphological characteristics, in-vitro controlled sustained drug release profiles during a period of seven days with acceptable maximum swelling index. Invivo, all cryobarriers were equivalent to each other concerning serum or tissue parameter. However, morphological and histopathological evaluations revealed that both xerocryogel and lyophilized cryofilms are more effective than the cryogel in prevention of post-operative peritoneal adhesions. The current study showed the possibility of preparing drug loaded cryobarriers using simple technique with an effective in vivo post-operative adhesion prevention.

Nanostructured lipid carriers for intraocular brimonidine localisation: development, in-vitro and in-vivo evaluation.

Brimonidine ocular hypotensive effect can be enhanced by increasing residence time and corneal penetration. The current work aimed to formulate, evaluate and compare nanostructured lipid carriers (NLCs) to solid lipid nanoparticles (SLNs) and commercial eye drops for controlled brimonidine delivery. NLCs prepared by modified high shear homogenisation were spherical with a mean size of 151.97 ± 1.98 nm, negative zeta potential (ZP) of -44.2 ± 7.81 mV, % entrapment efficiency (EE) of 83.631 ± 0.495% and low crystallinity index (CI) (17.12%), indicating a better drug incorporation. Moreover, they kept stable during storage at 4 °C for 3 months. Permeability coefficient of NLCs was 1.227 folds higher than that of SLNs. Histological examination revealed localisation of NLCs in the anterior ocular chamber. NLCs revealed the most sustained and highest intraocular pressure (IOP) lowering activity (-13.14 ± 1.28 mmHg) in rabbits. In conclusion, NLCs is a promising approach for IOP reduction compared to eye drops and SLNs.

Nanotechnology-based drug delivery systems for Alzheimer's disease management: Technical, industrial, and clinical challenges.

Alzheimer's disease (AD) is a neurodegenerative disease with high prevalence in the rapidly growing elderly population in the developing world. The currently FDA approved drugs for the management of symptomatology of AD are marketed mainly as conventional oral medications. Due to their gastrointestinal side effects and lack of brain targeting, these drugs and dosage regiments hinder patient compliance and lead to treatment discontinuation. Nanotechnology-based drug delivery systems (NTDDS) administered by different routes can be considered as promising tools to improve patient compliance and achieve better therapeutic outcomes. Despite extensive research, literature screening revealed that clinical activities involving NTDDS application in research for AD are lagging compared to NTDDS for other diseases such as cancers. The industrial perspectives, processability, and cost/benefit ratio of using NTDDS for AD treatment are usually overlooked. Moreover, active and passive immunization against AD are by far the mostly studied alternative AD therapies because conventional oral drug therapy is not yielding satisfactorily results. NTDDS of approved drugs appear promising to transform this research from 'paper to clinic' and raise hope for AD sufferers and their caretakers. This review summarizes the recent studies conducted on NTDDS for AD treatment, with a primary focus on the industrial perspectives and processability. Additionally, it highlights the ongoing clinical trials for AD management.

Effect of sterilization on the physical stability of brimonidine-loaded solid lipid nanoparticles and nanostructured lipid carriers.

Nanoparticulate delivery systems have recently been under consideration for topical ophthalmic drug delivery. Brimonidine base-loaded solid lipid nanoparticles and nanostructured lipid carrier formulations were prepared using glyceryl monostearate as solid lipid and were evaluated for their physical stability following sterilization by autoclaving at 121°C for 15min. The objective of this work was to evaluate the effect of autoclaving on the physical appearance, particle size, polydispersity index, zeta potential, entrapment efficiency and particle morphology of the prepared formulations, compared to non-autoclaved ones. Results showed that, autoclaving at 121°C for 15min allowed the production of physically stable formulations in nanometric range, below 500nm suitable for ophthalmic application. Moreover, the autoclaved samples appeared to be superior to non-autoclaved ones, due to their increased zeta potential values, indicating a better physical stability. As well as, increased amount of brimonidine base entrapped in the tested formulations.