Tadalafil Nanoemulsion Mists for Treatment of Pediatric Pulmonary Hypertension via Nebulization.

Oral tadalafil (TD) proved promising in treating pediatric pulmonary arterial hypertension (PAH). However, to ensure higher efficacy and reduce the systemic side effects, targeted delivery to the lungs through nebulization was proposed as an alternative approach. This poorly soluble drug was previously dissolved in nanoemulsions (NEs). However, the formulations could not resist aqueous dilution, which precluded its dilution with saline for nebulization. Thus, the current study aimed to modify the previous systems into dilutable TD-NEs and assess their suitability for a pulmonary application. In this regard, screening of various excipients was conducted to optimize the former systems; different formulations were selected and characterized in terms of physicochemical properties, nebulization performance, stability following sterilization, and biocompatibility. Results showed that the optimal system comprised of Capmul-MCM-EP:Labrafac-lipophile (1:1) (w/w) as oil, Labrasol:Poloxamer-407 (2:1) (w/w) as surfactant mixture (Smix) and water. The optimum formulation P2TD resisted aqueous dilution, exhibited reasonable drug loading (2.45 mg/mL) and globule size (25.04 nm), acceptable pH and viscosity for pulmonary administration, and could be aerosolized using a jet nebulizer. Moreover, P2TD demonstrated stability following sterilization and a favorable safety profile confirmed by both in-vitro and in-vivo toxicity studies. These favorable findings make P2TD promising for the treatment of pediatric PAH.

Community pharmacists' perceptions, awareness and practices regarding counterfeit medicines: a cross-sectional survey in Alexandria, Egypt.

BACKGROUND: Counterfeit medicines are a threat to public health and the national economy in Egypt. The many community pharmacists in the country could help prevent counterfeit medicines reaching the patient. Information on community pharmacists' perceptions of counterfeit medicines is lacking. AIMS: This study assessed the awareness, practices and perceptions of community pharmacists in Alexandria, Egypt with regard to counterfeit medicines. The aim was to identify gaps and inadequacies in pharmacy practice that might allow infiltration of counterfeit medicines in the legitimate medicine supply chain. METHODS: A cross-sectional study was conducted of 175 community pharmacists in Alexandria in 2014-2015. A semi-structured interview questionnaire was used to assess their perceptions, awareness and practices. The chi-squared test was used to assess the relationships between selected pharmacists' characteristics and their awareness, purchasing practice and training related to counterfeit medicines. RESULTS: Most pharmacists thought medicine counterfeiting was widespread in Egypt and that they could contribute to combatting the problem. However, most also lacked a clear perception of counterfeit medicines, an awareness of their danger to patients or the legislation to reduce them. Their procurement practices and detection of counterfeit medicines and handling of incidents of counterfeit medicines were inadequate. Pharmacists who thought counterfeit medicines were widespread or a health threat were significantly more likely to purchase medicines from certified sources (P < 0.05). CONCLUSION: Pharmacists should be developed as a frontline resource to combat counterfeit medicines. To enhance their role, the pharmacy curriculum needs to be updated and continuing professional development activities mandated.

Intranasal Tadalafil nanoemulsions: formulation, characterization and pharmacodynamic evaluation.

This study aims at improving the bioavailability of a poorly soluble phosphodiesterase-5 inhibitor; tadalafil (TD) via developing intranasal (IN) nanoemulsions (NEs). Optimum NE ingredients were selected based on solubility studies, emulsification tests, and phase diagram construction. Both o/w and w/o NEs were selected based on their drug loading capacity. Optimum formulations were subjected to physicochemical characterization and were assessed for nasal toxicity through biochemical analysis of tumor necrosis factor-α (TNF-α) and caspase-3 in rat nasal tissues. Pharmacodynamic study was performed via biochemical analysis of cyclic guanosine monophosphate (cGMP) in rat penis 2-h post-treatment and compared with oral suspension of Cialis® tablets. Optimum o/w and w/o NEs were successfully prepared using different ratios of Capmul-MCM-EP, Labrasol:Transcutol-HP (1:1) and water. Optimized formulations exhibited more than 4000-fold increase in TD solubility compared with its aqueous solubility. Both formulations were optically isotropic with the majority of globules in the nanometric-size range. Nasal toxicity study revealed no significant difference in values of TNF-α and caspase-3 between the NE-treated groups and the control group. Both TD-NEs succeeded to achieve a significant enhancement in cGMP levels. Our findings suggested that IN administration of the developed TD-NEs could provide a safe and effective alternative to TD oral delivery.

Self-emulsifying preconcentrates of daidzein-phospholipid complex: design, in vitro and in vivo appraisal.

AIM: Self-emulsifying phospholipid-complex preconcentrates (SEPPs) were fabricated to improve oral bioavailability of daidzein (DAI), an anticancer drug with challenging amphiphobic nature and extensive presystemic metabolism. METHODS: DAI-phosphatidylcholine complex was prepared to enhance DAI lipophilicity and loading in SEPPs. The physicochemical characteristics and the pharmacokinetic behavior in rats were studied. RESULTS: Surfactant-free SEPP (plain DAI:Phosal® 53MCT complex) was monodisperse upon aqueous dilution with nanorange globule size (485 ± 15 nm). Compared with drug suspension, it showed enhanced drug release and 2.38-fold enhanced oral bioavailability with minimized drug-induced intestinal irritation. Addition of 30% surfactant/co-surfactant mixture did not show any significant difference in drug release rate or absorption profile. CONCLUSION: The highly safe surfactant-free SEPP could be an effective approach to improve DAI oral bioavailability.

Photosensitizer-eluting nanofibers for enhanced photodynamic therapy of wounds: A preclinical study in immunocompromized rats.

Electrospun nanofibers (NFs) as drug delivery/tissue regeneration template and antimicrobial photodynamic therapy (APDT) have been widely investigated as two different approaches to enhance wound healing. In the present study, the two approaches were combined in a single platform for greater healing enhancement potentials. Composite photosensitizer-eluting NFs were developed using a polyhydrohybutyrate/polyethylene glycol (60:40 PHB/PEG) polymer blend and methylene blue (MB) as antimicrobial photosensitizer (PS). NFs protected the photoactivity of entrapped MB, enhanced its photodynamic activity against two wound bacteria, Staphylococcus aureus standard strain (SAst) and MRSA and sustained MB release allowing for flexible PS dosing and irradiation schedules. This combined PS-eluting NFs/APDT approach proved effective in the treatment of SAst-inoculated excision wounds in a challenging immunocompromized rat model. This was verified by morphological, morphometric, microbiological, histopathological and RT-PCR studies. Inclusion of PS-eluting NFs as an additional active component of APDT generates a combined non-antibiotic antimicrobial/cell regeneration approach with great potentials for wound healing and other biomedical applications.

Inhibition of postsurgical adhesions by methylene blue-loaded nanofibers versus cast film matrices.

In the quest for barrier membranes for the prevention of post-surgical tissue adhesions, polymer matrices may provide a platform of biomaterials with versatile properties. However, the relationship between the anti-adhesion effects of different polymer matrices and their physicochemical and structural properties is not yet adequately understood. In a preclinical study using a rat cecum model, we directly compared the anti-adhesion potential of polyhydroxybutyrate (PHB) electrospun nanofibrous versus cast film matrices loaded with methylene blue (MB) as antioxidant adhesion inhibitor. PHB retained MB presumably forming MB-bioactivated matrices. In the preclinical study, quantitative morphologic assessment in addition to histopathologic and SEM examinations 14 days post-surgery indicated that plain PHB NFs and MB-PHB NFs, moderately enhanced cecal wall healing and inhibited adhesion formation. In contrast, reshaping PHB as cast films, significantly enhanced healing, reduced adhesion bands and prevented inter-visceral adhesions. Cast films also inhibited tissue attachment to the matrix recovered 14 days post-surgery. Both PHB matrix types reduced tissue inflammation. Despite tissue anti-adhesion potential of individual matrix components, modulation of the micro-architectural properties generated polymer barriers with varying tissue anti-adhesion and healing potentials, the MB-loaded cast film achieving the best outcome.