Search

Drug covalently bound to polymers had formed, lately, platforms with great promise in drug delivery. These drug polymer conjugates (DPC) boosted drug loading and controlled medicine release with targeting ability. Herein, the ability of entecavir (E) conjugated to hyaluronic acid (HA) forming the core of vitamin E coated lipid nanohybrids (EE-HA LPH), to target Kupffer cells and hepatocyte had been proved. The drug was associated to HA with efficiency of 93.48 ± 3.14 % and nanohybrids loading of 22.02 ± 2.3 %. DiI labelled lipidic nanohybrids improved the macrophage uptake in J774 cells with a 21 day hepatocytes retention post intramuscular injection. Finally, in vivo biocompatibility and safety with respect to body weight, organs indices and histopathological alterations were demonstrated. Coating with vitamin E and conjugation of E to HA (a CD44 ligand), could give grounds for prospective application for vectored nano-platform in hepatitis B.

Global trials are grappling toward identifying prosperous remediation against the ever-emerging and re-emerging pathogenic respiratory viruses. Battling coronavirus, as a model respiratory virus, via repurposing existing therapeutic agents could be a welcome move. Motivated by its well-demonstrated curative use in herpes simplex and influenza viruses, utilization of the nanoscale zinc oxide (ZnO) would be an auspicious approach. In this direction, ZnO nanoparticles (NPs) were fabricated herein and relevant aspects related to the formulation such as optimization, structure, purity, and morphology were elucidated. In silico molecular docking was conducted to speculate the possible interaction between ZnO NPs and COVID-19 targets including the ACE2 receptor, COVID-19 RNA-dependent RNA polymerase, and main protease. The cellular internalization of ZnO NPs using human lung fibroblast cells was also assessed. Optimized hexagonal and spherical ZnO nanostructures of a crystallite size of 11.50 ± 0.71 nm and positive charge were attained. The pure and characteristic hexagonal wurtzite P63mc crystal structure was also observed. Interestingly, felicitous binding of ZnO NPs with the three tested COVID-19 targets, via hydrogen bond formation, was detected. Furthermore, an enhanced dose-dependent cellular uptake was demonstrated. The obtained results infer a rationale, awaiting validation from further biological and therapeutic studies.

Ear-oriented therapeutics vehiculation strategies are requisites for effective treatment of various otic ailments including otitis media (OM). Conquering minimal permeability of the intrinsic barrier of middle ear; intact tympanic membrane (TM) is still a defiance. In this study, the fabrication of glycerosomes was explored to boost triamcinolone acetonide (TA) delivery to the middle ear via the otic application to improve treatment of OM. Opting a d-optimal design, TA glycerosomes were formulated and optimized using ethanol injection method. The optimized formula was assessed for morphology, viscosity, ex vivo TM permeation and deposition and physical stability. Moreover, OM induction in rats using lipopolysaccharides was conducted, histological and biochemical investigations were performed to assess the therapeutic potential of TA glycerosomes and their tolerability as well. The optimized formula displayed a nanosized value (106.1 ± 2.82), low polydispersity index (0.079 ± 0.04), satisfactory drug entrapment efficiency (80.62 ± 4.41 %), shear thinning behavior and excellent physical stability. Ex-vivo TM permeation and deposition monitoring for 24 h demonstrated greater flux and deposition compared to free drug. More importantly, the in vivo studies demonstrated the supremacy of glycerosomes with respect to tolerability and efficacy in alleviating OM following ototopical application compared to marketed drug. Such therapeutic modality represents a promising option to boost the efficacy of otic drugs, awaiting clinical translation.

Gamma oryzanol (ORZ) is a nutraceutical that is poorly water soluble with poor intestinal absorption. In the current work, ORZ was nanoformulated into uncoated and chitosan coated micelles based on methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (mPEG-PCL) and poly(ε-caprolactone)-b-methoxy-poly(ethylene glycol)-b-poly(ε-caprolactone) (PCL-PEG-PCL) copolymers for augmenting ORZ oral delivery. The physicochemical properties, morphological study, in-vitro release and safety of the nanoplaforms were determined. Importantly, the nephroprotective competence of the nanoplaforms was analyzed against acute kidney injury (AKI) rat model and the sirtuin-1 associated machineries were assessed. The results revealed that the micelles exerted particle size (PS) from 97.9 to 117.8 nm that was markedly increased after chitosan coating. The reversal of zeta potential from negative to highly positive further confirmed efficient coating. In vitro release profiles demonstrated prolonged release pattern. The nanoforms conferred higher cell viability values than free ORZ on Vero cell line. The designed micelles displayed augmented nephroprotection compared to free ORZ with the supremacy of CS coated micelles over uncoated ones in restoring kidney parameters to normal levels. The attenuated AKI was fulfilled via the modulation of sirtuin-1 signaling pathways translated by restoring the histological features, increasing renal antioxidant states, renal autophagy and decreasing renal inflammation and renal apoptosis. These outcomes confirmed that surface modification with chitosan had a considerable leverage on micelles safety, release behavior and in vivo performance.

In recent years, researchers are exploring innovative green materials fabricated from renewable natural substances to meet formulation needs. Among them, biopolymers like chitosans and biosurfactants such as sugar fatty acid esters are of potential interest due to their biocompatibility, biodegradability, functionality, and cost-effectiveness. Both classes of biocompounds possess the ability to be efficiently employed in wound dressing to help physiological wound healing, which is a bioprocess involving uncontrolled oxidative damage and inflammation, with an associated high risk of infection. In this work, we synthesized two different sugar esters (i.e., lactose linoleate and lactose linolenate) that, in combination with chitosan and sucrose laurate, were evaluated in vitro for their cytocompatibility, anti-inflammatory, antioxidant, and antibacterial activities and in vivo as wound care agents. Emphasis on Wnt/β-catenin associated machineries was also set. The newly designed lactose esters, sucrose ester, and chitosan possessed sole biological attributes, entailing considerable blending for convenient formulation of wound care products. In particular, the mixture composed of sucrose laurate (200 µM), lactose linoleate (100 µM), and chitosan (1%) assured its superiority in terms of efficient wound healing prospects in vivo together with the restoring of the Wnt/β-catenin signaling pathway, compared with the marketed wound healing product (Healosol®), and single components as well. This innovative combination of biomaterials applied as wound dressing could effectively break new ground in skin wound care.

The aim of the current investigation is to delineate the buccal applicability of an in situ composite gel containing aceclofenac (AC) amino methacrylate copolymer microparticles (MPs), surm...

This study aims to obtain an inhalation powder with meaningful aerodynamic and safety profiles for the lung delivery of losartan (LS). For this, the capacity of self-assembly of chitosan (CS) and dextran sulfate (DS) to form CS/DS microplex (MC), incorporating high payload of hydrophilic LS was harnessed. Dry powder inhaler (LS-MC-DPI), prepared via spray drying of the best achieved LS-MC, was proposed to impart precise engineered inhalation characteristics. Micrometric robust CS/DS MC was revealed to offer the opportunity to heighten LS encapsulation, accounting for ~75%. LS-MC-DPI was successfully developed with high yield, flowability, respirable aerodynamic size and morphology which formed swellable and mucoadhesive network, facilitating intra-pulmonary delivery. Moreover, sustained release pattern, augmented deep lung deposition and safe histological profile were realized. Overall, the newly developed LS-MC DPI shows promises as an inhalation system. The aerodynamic performance and safety of LS-MC-DPI verify its suitability for further in vivo lung therapeutics.

Methoxy-poly(ethylene glycol)-b-poly(e-caprolactone) (mPEG-PCL) polymeric micelles (PMs) open a promising avenue through which ocular drug delivery with superior efficacy and tolerability can be potentially obtained. Methazolamide (MTZ) is an anti-glaucoma drug exhibiting poor corneal penetration, making it an ideal candidate for new polymeric micellar systems. MTZ-PMs were prepared using the thin film hydration procedure and optimized using a Design of Experiment (DoE) approach. In vitro drug release, thermal analyses and FT-IR characterization were also evaluated. MTT assay and histopathological assessment were carried out to verify ocular tolerability as well as Draize irritancy test. In vivo studies were conducted on rabbits to evaluate anti-glaucoma activity in a glucocorticoid-induced glaucoma model. The results showed successful entrapment of MTZ inside PMs matrix as reflected by the complete vanishing of drug melting peak in DSC thermogram and the possible formation of hydrogen bonding between MTZ and mPEG-PCL copolymer in FT-IR spectrum. The selected formula exhibited a particle size of 60 nm, entrapment efficiency of 93% and discrete spherical particles. Moreover, sustained release of MTZ, cellular and tissue biocompatibility and marked anti-glaucoma efficacy, as compared to MTZ solution, were realized. The combined results show that PMs could potentiate the therapeutic outcome of nanotechnology ocular drug delivery.

Surfactants are versatile excipients, which are commonly employed in several pharmaceutical formulations as emulsifiers, stabilizing or solubilizing agents. In this field, current research is aimed at the design or discovery of amphiphilic molecules with improved characteristics in terms of safety (toxicological profile) and biological activities (e.g. antimicrobial activity, interaction with biomembranes). Quaternary ammonium surfactants derived from amino acids are one such class of compounds with significant potential for pharmaceuticals. In this work, quaternary ammonium surfactants derived from the amino acids leucine and methionine and esterified with fatty acids of different lengths (C10, C12 and C14) were synthesized. These amphiphiles were characterized in terms of critical micelle concentration (CMC) by tensiometry and conductivity measurements, cytotoxicity (MTS and LDH assay on Caco-2 and Calu-3 cell lines) and antimicrobial activity on selected Gram-positive (S. aureus and E. faecalis), Gram-negative (E. coli and P. aeruginosa) and the fungus C. albicans. The derivatives bearing a C12 or a C14 chain displayed CMC, EC50 (from cytotoxicity assays) and minimum inhibition concentration (MIC) values that are comparable to those of benzalkonium chloride (used as reference), especially towards Gram-positive and C. albicans. On the contrary, derivatives bearing a C10 chain have higher CMC, EC50 and MIC values, highlighting the crucial role of the hydrophobic tail in determining both physicochemical and biological properties. The C12-C14 synthesized derivatives may represent a promising alternative to benzalkonium chloride as surface active molecules and antimicrobial agents.

Poly(lactic acid) (PLA) and poly(lactic-co-glycolic acid) (PLGA) are among the well-documented FDA-approved polymers used for the preparation of safe and effective vaccine, drug and gene delivery systems using well-described reproducible methods of fabrication. Various nano and microparticulates are fabricated using these polymers. Their successful performance relies on PLA and PLGA biocompatibility and degradability characteristics. This review provides an overview of the biocompatibility and biodegradation of PLA, PLGA and their copolymers, with a special emphasis on tissue responses for these polymers as well as their degradation pathways and drug release models. Moreover, the potential of PLA and PLGA based nano and microparticulates in various advanced biomedical applications is highlighted. PLA and PLGA based delivery systems show promises of releasing different drugs, proteins and nucleic acids in a stable and controlled manner and greatly ameliorating their therapeutic efficacy. In addition, advancement in surface modification and targeting of nanoparticles has extended the scope of their utility.

Fighting malignant neoplasms via repurposing existing drugs could be a welcome move for prosperous cancer remediations. In the current work, nanovehiculation and optimization of the repositioned itraconazole (ITZ) utilizing ascorbyl palmitate (AP) aspasomes would be an auspicious approach. Further, the optimized aspasomes were incorporated in a cream and tracked for skin deposition. The in vivo efficacy of aspasomal cream on mice subcutaneous Ehrlich carcinoma model was also assessed. The optimized aspasomes revealed nano size (67.83 ± 6.16 nm), negative charge (-79.40 ± 2.23 mV),95% ITZ entrapment and high colloidal stability. AP yielded substantial antioxidant capacity and pushed the ITZ cytotoxicity forward against A431 cells (IC

The present study is concerned with the suitability of using Myrj 59, out-performing the commonly used stabilizer i.e., poloxamer, for preparation of cubosomes on one hand and gives an insight into the need for distinctive choice of delivery system and administration route towards better diabetes pharmacotherapy on the other hand. In light, repaglinide (REP) cubosomal dispersion and in-situ gel forms were prepared and physicochemically characterized. The selected cubosomal forms were tested for in-vitro drug release and administered via intranasal (IN) and intraperitoneal (IP) routes and compared with Intravenous (IV) REP solution regarding in-vivo antidiabetic efficacy. The results confirmed the formation of cubic nanostructures (170−233 nm), entrapping high REP amounts (93.2–95.66 %). Sustained REP release from selected cubosomal forms was realized with no burst release. Upon in-vivo assessment, IN and IP REP cubosomes and cubosomal gel exhibited superior long-acting in-vivo traits over IV REP solution, respecting percentages of maximum reduction, total decrease in BG levels, and the pharmacological availability. Moreover, IP REP cubosomes and cubosomal gel revealed higher values of the aforementioned parameters than IN counterparts. In conclusion, IN and IP administration of the newly developed cubosomal forms could proffer feasible options for an optimal control of BG levels.

Flavonoids possess different interesting biological properties, including antibacterial, antiviral, anti-inflammatory and antioxidant activities. However, unfortunately, these molecules present different bottlenecks, such as low aqueous solubility, photo and oxidative degradability, high first-pass effect, poor intestinal absorption and, hence, low systemic bioavailability. A variety of delivery systems have been developed to circumvent these drawbacks, and among them, in this work niosomes have been selected to encapsulate the hepatoprotective natural flavonoid quercetin. The aim of this study was to prepare nanosized quercetin-loaded niosomes, formulated with different monolaurate sugar esters (i.e., sorbitan C12, glucose C12, trehalose C12, sucrose C12) that act as non-ionic surfactants and with cholesterol as stabilizer (1:1 and 2:1 ratio). Niosomes were characterized under the physicochemical, thermal and morphological points of view. Moreover, after the analyses of the in vitro biocompatibility and the drug-release profile, the hepatoprotective activity of the selected niosomes was evaluated in vivo, using the carbon tetrachloride (CCl4)-induced hepatotoxicity in rats. Furthermore, the levels of glutathione and glutathione peroxidase (GSH and GPX) were measured. Based on results, the best formulation selected was glucose laurate/cholesterol at molar ratio of 1:1, presenting spherical shape and a particle size (PS) of 161 &plusmn, 4.6 nm, with a drug encapsulation efficiency (EE%) as high as 83.6 &plusmn, 3.7% and sustained quercetin release. These niosomes showed higher hepatoprotective effect compared to free quercetin in vivo, measuring serum biomarker enzymes (i.e., alanine and aspartate transaminases (ALT and AST)) and serum biochemical parameters (i.e., alkaline phosphatase (ALP) and total proteins), while following the histopathological investigation. This study confirms the ability of quercetin loaded niosomes to reverse CCl4 intoxication and to carry out an antioxidant effect.

Background: Due to its unique features, the respiratory tract had received great attention as a promising non-invasive route for drug administration to achieve both local and systemic effects. Efforts spent to tailor systems able to overcome the lung defence mechanisms and biological barriers are followed in this review. Aerodynamic diameter, morphology, lung deposition and drug release profiles are the main criteria describing the selected new smart lung targeted delivery systems. Methods: Novel systems such as nanoparticles, nano-embedded-in microparticles (NEM), small microparticles (MP), large porous particles (LPP), PulmospheresTM and polymeric micelles are used to passively target different areas in the respiratory tract. The most common preparation methods are outlined in the article. Special emphasis was given to the characteristics of the polymers used to fabricate the developed systems. Efforts made to prepare systems using chitosan (CS), alginate (alg), hyaluronic acid (HA), gelatin and albumin as examples of natural polymers and poly lactic-co-glycolic acid (PLGA) and poly(Ɛ-caprolactone) (PCL) as synthetic polymers were compiled. Conclusion: The continuous development and work in the area of lung targeting resulted in the development of engineered smart platforms with the capability to carry small drug molecules, proteins and genes to treat a variety of local and systemic diseases.

Tazarotene (TAZ) is a topical synthetic retinoid used in psoriasis treatment, however, it is extremely lipophilic and exhibits skin irritation. Research is in a state of continuous advancement in the field of nanocarriers fabrication, and in this regard, we investigated the formulation of novel topically oriented nanovesicles; representing a combination of spanlastics and penetration enhancer vesicles, to be termed (fluidized-SNs). TAZ-loaded fluidized SNs were physicochemically characterized, tested for ex vivo cutaneous retention, and the selected formulation was compared with the marketed product Acnitaz® regarding clinical antipsoriatic activity. The selected fluidized-SNs enriched with 1% cineole exhibited high entrapment for TAZ (76.19%), suitable size and zeta potential of 241.5 ± 5.68 nm and −36.10 ± 2.50 mV respectively, and retaining of stability after refrigeration storage for one month. As hypothesized, cineole enriched fluidized-SNs exhibited remarkable TAZ deposition amounting to a total of 81.51% in the different skin layers. Upon clinical assessment, the presented formulation displayed superior traits compared to the marketed product, in terms of dermoscopic imaging, morphometric analysis of psoriatic lesions, and statistical analysis of PASI scores. Results confirmed that the prepared novel fluidized spanlastics formulation holds great promise for the treatment of psoriasis, and its benefit should futuristically be investigated in other topical diseases.

Introduction: The applications of naturally obtained polymers are tremendously increased due to them being biocompatible, biodegradable, environmentally friendly and renewable in nature. Among them, polyhydroxyalkanoates are widely studied and they can be utilized in many areas of human life research such as drug delivery, tissue engineering, and other medical applications. Areas covered: This review provides an overview of the polyhydroxyalkanoates biosynthesis and their possible applications in drug delivery in the range of micro- and nano-size. Moreover, the possible applications in tissue engineering are covered considering macro- and microporous scaffolds and extracellular matrix analogs. Expert commentary: The majority of synthetic plastics are non-biodegradable so, in the last years, a renewed interest is growing to develop alternative processes to produce biologically derived polymers. Among them, PHAs present good properties such as high immunotolerance, low toxicity, biodegradability, so, they are promisingly using as biomaterials in biomedical applications.

Dendrimers are highly branched macromolecular nanosized molecules prepared by polymer synthesis at a very high level of control, to produce symmetric molecules with monodisperse structures that possess an exterior surface rich in different end groups. They have been widely utilized in several applications to date, owing to their solubilization, conjugation, and ligand-binding potential, as well as the possibility of linking them to many pharmacokinetic modifiers. The term composite refers to the combination of materials of different properties, to yield other new systems with even more unique properties. “Composite dendrimers” are a newly introduced system made of synthetic dendritic polymers in conjunction with either organic or inorganic entities. In this chapter a highlight on the published work related to “composite dendrimers” will be made, while contrasting their applications to mere dendrimers, with details on the aforementioned state of the art.

The aim of this work was to obtain an intranasal delivery system with improved mechanical and mucoadhesive properties that could provide prolonged retention time for the delivery of risedronate (RS). For this, novel in situ forming gels comprising thermo-responsive star-shaped polymers, utilizing either polyethylene glycol methyl ether (PEGMA-ME 188, Mn 188) or polyethylene glycol ethyl ether (PEGMA-EE 246, Mn 246), with polyethylene glycol methyl ether (PEGMA-ME 475, Mn 475), were synthesized and characterized. RS was trapped in the selected gel-forming solutions at a concentration of 0.2% w/v. The pH, rheological properties, in vitro drug release, ex vivo permeation as well as mucoadhesion were also examined. MTT assays were conducted to verify nasal tolerability of the developed formulations. Initial in vivo studies were carried out to evaluate anti-osteoporotic activity in a glucocorticoid induced osteoporosis model in rats. The results showed successful development of thermo-sensitive formulations with favorable mechanical properties at 37 °C, which formed non-irritant, mucoadhesive porous networks, facilitating nasal RS delivery. Moreover, sustained release of RS, augmented permeability and marked anti-osteoporotic efficacy as compared to intranasal (IN) and intravenous (IV) RS solutions were realized. The combined results show that the in situ gels should have promising application as nasal drug delivery systems.

Floating famotidine loaded mineral oil-entrapped emulsion gel (MOEG) beads were prepared by the emulsion–gelation method. Different polysaccharides (sodium alginate and pectin), oil concentrations (10%, 20% and 30% w/w) and drug:polymer (D:P) ratios (1:1, 2:1 and 3:1) were used and their influence on beads uniformity, drug entrapment efficiency (DEE) and in vitro drug release, was studied. The results clearly indicated that retardation of drug release for 4 h was achieved by the oil hydrophobic diffusional barrier, especially in the presence of the compact network of alginate beads. Calcium alginate beads containing 20% oil and 2:1 D:P ratio, showed an optimum DEE of 88.32%. When evaluated in vivo, this formula displayed superior antiulcer activity (>2) over drug suspension or marketed conventional tablets.

Polysaccharides, which have been explored to possess gelling properties and a wide margin of safety, were used to formulate single-unit floating matrix tablets by a direct compression technique. This work has the aim to allow continuous slow release of famotidine above its site of absorption. The floating approach was achieved by the use of the low density polypropylene foam powder. Polysaccharides (kappa-carrageenan, gellan gum, xyloglucan, and pectin) and blends of polysaccharides (kappa-carrageenan and gellan gum) and cellulose ethers (hydroxypropylmethyl cellulose, hydroxypropylcellulose, sodium carboxymethyl cellulose) were tried to modulate the release characteristics. The prepared floating tablets were evaluated for their floating behavior, matrix integrity, swelling studies, in vitro drug release studies, and kinetic analysis of the release data. The differential scanning calorimetry and Fourier transform infrared spectroscopy studies revealed that changing the polymer matrix system by formulation of polymers blends resulted in formation of molecular interactions which may have implications on drug release characteristics. This was obvious from the retardation in drug release and change in its mechanistics.

Enas Elmowafy, Rihab Osman, Abdel Hameed El-Shamy,† Gehanne AS AwadDepartment of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt†Abdel Hameed El-Shamy passed away on August 25, 2013Abstract: The aim of the present work was to test the ability of two non-diabetogenic ­carbohydrates to intranasally deliver the insulinotropic drug repaglinide (REP) for controlling blood glucose level. REP was loaded onto chitosan/alginate nanocomplexes (NCs) suitable for mucosal delivery and uptake. Improved stability and delivery characteristics were obtained by spray drying the selected NCs, yielding microparticles. A statistical experimental design was adopted to investigate the effects of the formulations’ variables on two critical responses: NC size and drug entrapment efficiency. Physicochemical characterizations of the network’s structures were done, and in vitro cytotoxicity and histopathological studies were conducted. The potential of the developed system to prolong the drug effect was tested on diabetic rats. The results showed that to attain particles suitable for nasal delivery, alginate should be used at its lowest level used in this study (0.6mg/mL). A low level of chitosan (0.5 mg/mL) was needed when the drug was cation-loaded, while the high chitosan level (1 mg/mL) was more suitable when REP was anion-loaded. The best entrapment efficiency was achieved at a theoretical drug loading of 0.025 mg/mL. Discrete NCs could be rapidly recovered from the spray-dried microparticles. The cytotoxicity and histopathological studies indicated that such formulations were well tolerated. The antihyperglycemic activity of the nasally administered formulae was gradual but was significantly sustained over 24hours, suggesting NC mucosal uptake. Nasal delivery of such dry powders achieved better glycemic control compared with the conventional oral tablets.Keywords: nanocomplexes, microparticles, spray drying, nasal delivery, antidiabetic effect

The aim of the present study was to load the post-prandial glucose regulator, repaglinide (REP), on spray dried mucoadhesive microparticles (MPs) comprising anionic polysaccharides. The formulation parameters of the polysaccharides-REP spray dried powders (SDP) namely, polysaccharide type and drug to polymer (D/P) ratio, were optimized for % release after 5 min (R%5 min) and time required for 80% release (T80%). The suitability of the selected formulae for nasal application was evaluated by ex vivo mucoadhesion, in vitro cytocompatability and tolerability studies. A pharmacodynamic study in diabetic rats was conducted. Results showed that both polysaccharide type and amount greatly influenced the chosen responses. REP was highly incorporated in mucoadhesive MPs with proven safety on the rat nasal mucosa. The selected REP loaded powders exhibited a significant two to threefold increase in total decrease in blood glucose compared to the nasal and intravenous solutions.