Magnetic Lipid-Based hybrid nanosystems: A combined stimuli- responsive nanocarriers for enriched chemotherapeutic potential of L-carnosine in induced breast Ehrlich ascites tumor model.

Magnetic Lipid-Based Hybrid Nanosystems (M-LCNPs) is a novel nanoplatform that can respond to magnetic stimulus and are designed for delivering L-carnosine (CN), a challenging dipeptide employed in the treatment of breast cancer. CN exhibits considerable water solubility and undergoes in-vivo degradation, hence restricting its application. Consequently, it is anticipated that the developed M-LCNPs will enhance the effectiveness of CN. To ensure the physical stability of MNPs, they were initially coated with a mixture of oleic acid and oleylamine before being included in pegylated liquid crystalline nanoparticles (PLCNPs). The proposed M-LCNPs exhibited promising in-vitro characteristics, notably a small particle size (143.5 nm ± 1.25) and a high zeta potential (-39.5 mV ± 1.54), together with superparamagnetic behavior. The in-vitro release profile exhibited a prolonged release pattern. The IC50 values of M-LCNPs were 1.57 and 1.59 times lower than these of the CN solution after 24 and 48 hours, respectively. Female BALB/C female mice with an induced breast cancer (Ehrlich Ascites tumor [EAT] model) were used to study the influence of an external magnetic field on the chemotherapeutic activity and toxicity of CN loaded in the developed M-LCNPs. Stimuli-responsive M-LCNPs exhibited no apparent systemic toxicity in addition to enhanced chemotherapeutic efficacy compared to nontargeted M-LCNPs and CN solution, as evidenced by a reduction of % tumor growth (11.7%), VEGF levels (22.95 pg/g tissue), and cyclin D1 levels (27.61 ng/g tissue), and an increase in caspase-3 level (28.9 ng/g tissue). Ultimately, the developed stimuli-responsive CN loaded M-LCNPs presented a promising nanoplatform for breast cancer therapy.

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.

Intranasal galantamine/chitosan complex nanoparticles elicit neuroprotection potentials in rat brains via antioxidant effect.

BACKGROUND: Alzheimer's disease is a common cause of dementia in the elderly. Galantamine hydrobromide (GH) is an anti-Alzheimer cholinesterase inhibitor that has an intrinsic antioxidant effect. In a previous study, GH was complexed with chitosan to prepare intranasal GH/chitosan complex nanoparticles (CX-NP2). The nanoparticles were located in rat brains 1 h after nasal administration and showed pharmacological superiority to GH nasal solution without showing histopathological toxicity. OBJECTIVE: This study aimed to investigate whether the long-term administration of CX-NP2 leads to biochemical toxicity in rat brains compared to GH nasal solution. METHODS: CX-NP2 dispersion and GH solution were administrated intranasally to male Wistar rats for 30 days (3 mg/kg/day). Malondialdehyde (MDA), lipid peroxidation marker, glutathione (GSH), superoxide dismutase (SOD) activity and tumor necrosis factor-α (TNF-α) were assessed in the brain extracts in all groups. RESULTS: There was statistically insignificant difference between the CX-NP2 and GH nasal solution treated groups in all biochemical toxicity parameters assessed. Interestingly, MDA and TNF-α levels in the CX-NP2-treated group significantly decreased compared to the control group. Also, GSH level and SOD activity were significantly enhanced in CX-NP2 treated group compared to the control group. CONCLUSIONS: CX-NP2 did not induce a statistically significant oxidative stress or neuroinflammation in rat brains after 30-day treatment, they rather elicited neuroprotective potentials.HighlightsIntranasal GH/chitosan complex nanoparticles (CX-NP2) show promising potential as a brain targeting carrier.Compared to GH nasal solution, nasal CX-NP2 formulation did not exert oxidative stress nor neuroinflammation when administered for 30 days.

Galantamine nanoparticles outperform oral galantamine in an Alzheimer's rat model: pharmacokinetics and pharmacodynamics.

Aim: Galantamine is an acetylcholinesterase inhibitor frequently used in Alzheimer's disease management. Its cholinergic adverse effects and rapid elimination limit its therapeutic outcomes. We investigated the pharmacodynamics and pharmacokinetics of 2-week intranasal galantamine-bound chitosan nanoparticles (G-NP) treatment in scopolamine-induced Alzheimer's disease rat model. Materials & methods: Behavioral, neurobiochemical and histopathological changes were assessed and compared with oral and nasal solutions. Brain uptake and pharmacokinetics were determined using a novel validated LC/MS assay. Results: G-NP enhanced spatial memory, exploring behavior and cholinergic transmission in rats. Beta-amyloid deposition and Notch signaling were suppressed and the histopathological degeneration was restored. G-NP potentiated galantamine brain delivery and delayed its elimination. Conclusion: G-NP hold promising therapeutic potentials and brain targeting, outperforming conventional galantamine therapy.

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.

Curcumin-loaded proniosomal gel as a biofreindly alternative for treatment of ocular inflammation: In-vitro and in-vivo assessment.

Ocular inflammation is a natural defensive phenomenon, but, it results in discomfort in the eye; as well as makes the eye vulnerable to other diseases. The aim of this work is to investigate that Curcumin (CUR) could be an effective safer biofreindly alternative for treatment of ocular inflammation. Complete in-vitro characterization of proniosomal gel loading-CUR using different surfactants was studied. A comparative in-vivo evaluation of selected formulation to a marketed corticosteroid drops in induced-eye inflammation model in rabbits was assessed. The selected formulation (FCr 300) composed of Cremophore RH surfactant, lecithin and cholesterol (9:9:1) loading CUR (1.2% w/w). The formulation showed mean PS(212.0 ± 0.1)nm, PDI (0.3 ± 0.1) , ZP(-5.1 ± 0.2)mV and % EE (96.0 ± 0.1). TEM showed multilamellar circular shaped niosomes with smooth surface. SEM showed ruptured vesicles for the lyophilized formula. Selected proniosomal gel showed enhanced permeability 3.22-fold and 1.76-fold higher than CUR dispersion and its lyophilized form respectively. Both proniosomal gel (FCr300) and corticosteroid drops reduced the induced inflammatory signs effectively by 40% on day-one and complete recovery on day-four. This anti-inflammatory result was confirmed by histopathological analysis after treatment. Assessment of cumulative IOP as a predicted side effect verified the goal of this work. In conclusion, the use of CUR as a natural biofreindly alternative to the current chemical conventional ocular anti-inflammatory treatment protocols is comparable as an anti-inflammatory drug with much less side effects.

Chemotherapeutic potential of L-carnosine from stimuli-responsive magnetic nanoparticles against breast cancer model.

Aim: L-carnosine-coated magnetic nanoparticles (CCMNPs) were developed to enhance chemotherapeutic activity of carnosine-dipeptide. Materials & methods: Surface grafting of MNPs with carnosine was contended by differential scanning calorimetry, infrared spectroscopy and x-ray diffraction. Physicochemical characterization and in vitro cytotoxicity on MCF-7 cell line was carried out. In vivo chemotherapeutic activity and toxicity was assessed by an Ehrlich Ascites tumor model. Results: CCMNPs possessed monodispersed size (120 nm), ζ (-27.3 mV), magnetization (51.52 emu/g) and entrapment efficiency (88.3%) with sustained release rate. CCMNPs showed 2.3-folds lower IC50 values compared with carnosine solution after 48 h. Targeted CCMNPs were specifically accumulated in tumor showing significant reduction in tumor size with no systemic toxicity. Significant reduction in VEGF and cyclin D1 levels were observed. Conclusion: The developed system endowed with responsiveness to an external stimulus can represent a promising magnetically targeted delivery system for carnosine site specific delivery.

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.

A new design for a chronological release profile of etodolac from coated bilayer tablets: In-vitro and in-vivo assessment.

Repeated dose medication usually maximizes adverse effects, while sustained release systems did not offer a fast onset of action. Etodolac was formulated to enable pulsatile and sustained drug release, which was chronologically more suitable as an anti-inflammatory drug. Eudragit® RSPO, Eudragit® RLPO, and HPMC K15M were added in the sustained release layer and tried in different ratios. Croscarmellose sodium or sodium starch glycolate were used as superdisintegrants for the fast release layer offering the loading dose for rapid onset of drug action. Bilayer tablets were successively coated with Opadry®II, HPMC K4M and E5 (1:40), and Surelease®. All formulations complied with the Pharmacopeial standards for post-compression parameters. In-vitro release profile illustrated a lag-time of 4 h followed by a rapid loading dose release for 2 h. A prolonged steady state release with a t1/2 of 11 h lastly occurred. The coated bilayer tablet showed pulsatile and sustained release effects in rats. The licking time and swelling degree were tested and results demonstrated significant difference (P < 0.05) between the sustained anti-inflammatory action of formulation C1 compared to other groups. Therefore the new chronological design could provide a consistent drug release over 24 h with good protection against associated symptoms of gastric release.

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.

Promote Recurrent Aphthous Ulcer Healing with Low Dose Prednisolone Bilayer Mucoadhesive Buccal Film.

BACKGROUND: Recurrent aphthous ulcer (RAU) is one of the most common ulcerative diseases of the oral mucosa which is recurrent, painful and slow to heal. Treatment is primarily for pain relief and promotion of healing to shorten the disease duration or reduce the rate of recurrence. OBJECTIVE: Development of a new design of topical buccal bilayer mucoadhesive films containing sodium alginate and gellan gum loaded with low dose of 1 mg prednisolone sodium phosphate to reduce the treatment period and decrease side effects of systemic treatment. METHODS: Films were prepared by solvent casting technique and evaluated to ensure optimum film characteristics, and in vivo efficiency. RESULTS: The bilayer films were thin, flexible with good water uptake, mucoadhesive and mechanical properties. In vitro drug release was sustained and showed anomalous non-Fickian kinetics. SEM confirmed the development of bilayer formation. Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetery indicated no chemical interaction between the layers. In vivo study in rabbits with induced oral ulceration showed complete ulcer healing within 4-5 days by once daily treatment of the studied film. Histological examination indicated no inflammation on treatment sites compared to inflamed tissue on the control sites. CONCLUSION: The results suggested that buccal application of the developed bilayer mucoadhesive films loaded with only 1mg of prednisolone provided mucoadhesive and convenient application and was able to promote RAU healing with shorter treatment duration.

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.

Pharmacological, toxicological and neuronal localization assessment of galantamine/chitosan complex nanoparticles in rats: future potential contribution in Alzheimer's disease management.

PURPOSE: Nasal galantamine hydrobromide (GH)/chitosan complex nanoparticles (CX-NP2) could have an improved therapeutic potential for managing Alzheimer's disease (AD). The current study aimed to investigate if the complexation reaction between GH and chitosan altered the pharmacological and toxicological profiles of the parent drug; GH. METHODS: The nasal administration of CX-NP2 to male Wistar rats for 12 consecutive days was compared to negative control group, and oral and nasal GH solutions treated groups in 3 mg/kg daily GH dose. Brain acetylcholinesterase (AChE) protein level and activity were assessed. The in vivo toxicity of CX-NP2 was evaluated via monitoring the clinical signs throughout the study. Histopathological examination of brain sections was performed. The intracellular localization of CX-NP2 within brain neurons was investigated using transmission electron microscopy. RESULTS: GH/chitosan complexation did not negatively alter the pharmacological efficiency of GH. Intriguingly, nasal CX-NP2 exhibited a significant decrease of AChE protein level and activity in rat brains compared to the oral and nasal GH solutions. No toxicity signs or histopathological manifestations were noticed. The nanoparticles were found intracellularly in the brain neurons. CONCLUSION: The pharmacological efficacy and in vivo safety of nasal CX-NP2 confirm their promising potential to contribute to the management of AD intranasally.

A new approach for treatment of precancerous lesions with curcumin solid-lipid nanoparticle-loaded gels: in vitro and clinical evaluation.

OBJECTIVE: Preparation and characterization of curcumin solid-lipid nanoparticle (CurSLN)-loaded mucoadhesive gel for local treatment of oral precancerous lesions with low dose. METHODOLOGY: The formulated CurSLNs were dispersed in a mucoadhesive gel matrix to be applied to the buccal mucosa. Conventional mucoadhesive gel using binary system was adopted. The prepared gels were evaluated for in vitro drug dialysis, ex vivo mucoadhesion test and ex vivo permeation study using chicken buccal mucosa. Short-term clinical evaluation was carried out on 10 patients suffering oral erythroplakia in terms of pain index and lesion size measurement. (1) RESULTS: The results showed that the loaded gel with CurSLN showed good mucoadhesion property and 25 min in vivo residence time. In addition to stability enhancement for the Cur powder. All formulae did not show any drug permeated, however, significant amount of Cur was retained within the chicken buccal mucosal tissue confirmed by histological examination. Significant reduction in pain, and complete healing was observed after 6 weeks of treatment. CONCLUSION: The local use of Cur in low dose is a promising option for treatment of precancerous lesions. The lack of local anti-inflammatory compounds with reduced side effects intensifies the importance of studying natural products for this purpose.

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.

Complexation as an approach to entrap cationic drugs into cationic nanoparticles administered intranasally for Alzheimer's disease management: preparation and detection in rat brain.

OBJECTIVE: Complexation was investigated as an approach to enhance the entrapment of the cationic neurotherapeutic drug, galantamine hydrobromide (GH) into cationic chitosan nanoparticles (CS-NPs) for Alzheimer's disease management intranasally. Biodegradable CS-NPs were selected due to their low production cost and simple preparation. The effects of complexation on CS-NPs physicochemical properties and uptake in rat brain were examined. METHODS: Placebo CS-NPs were prepared by ionic gelation, and the parameters affecting their physicochemical properties were screened. The complex formed between GH and chitosan was detected by the FT-IR study. GH/chitosan complex nanoparticles (GH-CX-NPs) were prepared by ionic gelation, and characterized in terms of particle size, zeta potential, entrapment efficiency, in vitro release and stability for 4 and 25 °C for 3 months. Both placebo CS-NPs and GH-CX-NPs were visualized by transmission electron microscopy. Rhodamine-labeled GH-CX-NPs were prepared, administered to male Wistar rats intranasally, and their delivery to different brain regions was detected 1 h after administration using fluorescence microscopy and software-aided image processing. RESULTS: Optimized placebo CS-NPs and GH-CX-NPs had a diameter 182 and 190 nm, and a zeta potential of +40.4 and +31.6 mV, respectively. GH encapsulation efficiency and loading capacity were 23.34 and 9.86%, respectively. GH/chitosan complexation prolonged GH release (58.07% ± 6.67 after 72 h), improved formulation stability at 4 °C in terms of drug leakage and particle size, and showed insignificant effects on the physicochemical properties of the optimized placebo CS-NPs (p > 0.05). Rhodamine-labeled GH-CX-NPs were detected in the olfactory bulb, hippocampus, orbitofrontal and parietal cortices. CONCLUSION: Complexation is a promising approach to enhance the entrapment of cationic GH into the CS-NPs. It has insignificant effect on the physicochemical properties of CS-NPs. GH-CX-NPs were successfully delivered to different brain regions shortly after intranasal administration suggesting their potential as a delivery system for Alzheimer's disease management.

Gelucire-Based Nanoparticles for Curcumin Targeting to Oral Mucosa: Preparation, Characterization, and Antimicrobial Activity Assessment.

The purpose of the study was to prepare and characterize curcumin (Cur) solid lipid nanoparticles (CurSLN) with a high-loading capacity and chemical stability for the treatment of oral mucosal infection. CurSLN were formulated using different lipids, namely, Gelucire 39/01, Gelucire 50/13, Precirol, Compritol, and poloxamer 407 as a surfactant. Formulae were evaluated for their entrapment efficiency, particle size, and ex vivo mucoadhesion test. Microbiological evaluation was carried out on six microorganisms, five of which are the most commonly affecting oral cavity in terms of determination of minimum inhibitory concentration (MIC), and minimum bactericidal concentration. Transmission electron microscopy was conducted for ultrathin section for Candida albicans-treated with formulated Cur. The results showed high entrapment efficiency and stability enhancement for Cur powder. Significant amount of Cur was retained onto the mucosal tissue indicating preferential mucosal uptake. CurSLN showed higher antimicrobial activity as compared with Cur raw material and chemically stabilized Cur where it showed MIC (0.185, 0.09375, 0.75, 3, 1.5, and 0.1875 mg/mL) against Staphylococcus aureus, Streptococcus mutans, Viridansstrept, Escherichia coli, Lactobacillus acidophilus, and Candida albicans, respectively. The prepared lipid nanoparticles maintained Cur chemical stability and microbiological activity. The lack of local antimicrobial therapeutics with minimum side effects augments the importance of studying natural products for this purpose.

Lyophilized sponges loaded with curcumin solid lipid nanoparticles for buccal delivery: Development and characterization.

This study aimed to prepare and evaluate mucoadhesive sponges as dosage forms for delivering solid lipid nanoparticles. For this purpose curcumin (Cur) was formulated as solid nanoparticles (SLN) using Gelucire 50/13, and polaxomer 407. The prepared CurSLN dispersion was thickened with different mucoadhesive polymers. Different concentrations of glycerol, and mannitol of range (0.25-20%), and (0-1%), respectively were also examined. The formed gel was poured into oblong molds and freeze dried to form mucoadhesive sponge to be applied to the buccal mucosa. The prepared sponges were evaluated for their, in-vivo residence time, in-vitro and in-vivo drug release, and hydration capacity. Surface morphology for the different sponges were examined using SEM. TEM was also carried out for sponge fragments previously dispersed into water. Infrared spectroscopy was conducted to investigate interaction between used ingredients. The results showed that the CurSLN loaded HPMC, and Polycarbophil sponges showed 4, and 15 h in-vivo residence time, respectively, providing a considerable amount of curcumin into saliva. The incorporation of glycerol and mannitol at concentration of 1% provided elegant and flexible sponges. The SEM showed that the deposition of CurSLN differed according to the type of polymer used. TEM confirmed the integrity of liberated CurSLN from sponges. IR spectra showed an interaction between HPMC and poloxamer 407, which affected its behavior as a gelling agent. The obtained results provide an efficient approach for delivering solid lipid nanoparticles in a solid dosage form keeping the nanoparticle characters and integrity.

Osteogenic effect of locally applied Pentoxyfilline gel: in vitro and in vivo evaluations.

The aim of this study was to formulate Pentoxyfylline drug (PTX) as a local bioadhesive Carbopol (Cbp) based gels for the aid of bone induction around an endosseus oral implant. The local delivery of the drug will probably avoid most of the problems associated with its systemic use including; disturbances in gastrointestinal tract and the central nervous system. Two concentrations of 1% and 3% Cbp containing 1% PTX were prepared. The gels were investigated for their physicochemical properties. Cbp based gels were found to be translucent with good homogeneity, uniform distribution of the drug and absence of any lumps. The pH of the gels was within neutrality, 7.1, which is considered to be acceptable to avoid the risk of any possible irritation in the oral cavity. The Cbp gels exhibited satisfactory bioadhesive properties and a pseudo-plastic rheological behavior. Cumulative drug released from the gels showed a controlled-release for more than 24 hours with the order of 3% >1% and the drug was released by diffusion mechanism from both gels. Statistical analysis revealed non-significant difference in drug content, rheological property and release rate of the stored gels for six months compared to the fresh ones. In vivo experimental results in rabbits have shown significant difference in bone depth induction of 3% and 1% Cbp gels with the formation of strong organized bone over the control group. Local administration of Pentoxifylline could be regarded as a valid approach in the management of osseointegration.

Nano-proniosomes enhancing the transdermal delivery of mefenamic acid.

Mefenamic acid (MA) is a BCS II class NSAID drug. It is available only in the form of tablets, capsules, and pediatric suspensions. Oral administration of MA is associated with severe gastrointestinal side effects. The aim of this study was to develop a convenient and low-cost transdermal drug delivery system for MA using proniosome as a novel carrier without the addition of penetration enhancers. The formulation factors, such as the presence of cholesterol, types of lecithin, and surfactants were investigated for their influence on the entrapment efficiency, rate of hydration, vesicle size, and zeta potential, in vitro drug release and skin permeation in order to optimize the proniosomal formulations with the minimum dose of the drug. Furthermore, the in vivo anti-inflammatory effect was evaluated on a formalin-induced rat paw edema model. The results showed that the type of surfactants had higher impact on the entrapment efficiency than the type of lecithins, with the highest in Span 80 (82.84%). The release of MA from Span 80 proniosomal gel was significantly affected by the type of lecithin used. The addition of cholesterol significantly increased both the drug release and the skin permeation flux of MA. Zeta potential showed a stable A4 noisomal suspension. DSC revealed the molecular dispersion of MA into the loaded proniosomes. In vivo study of the treatment group with MA proniosome gel showed a significant inhibition of rat paw edema compared with the same gel without the drug (control). The results of this study suggest that proniosomes are promising nano vesicular carriers and safe alternatives to enhance the transdermal delivery of MA.