Non-invasive caffeinated-nanovesicles as adipocytes-targeted therapy for cellulite and localized fats.

Caffeine (CAF) is a non-selective adenosine A1 receptor antagonist which predominates in fat cells. When CAF binds to adenosine receptors, it increases cyclic adenosine monophosphate; inhibiting adipogenesis and inducing fat lipolysis. Resveratrol (RSV) is an antioxidant polyphenol possessing different anti-obesity mechanisms. Topical application of both hydrophilic CAF and lipophilic RSV is limited. This study aimed to develop novel caffeinated-resveratrol bilosomes (CRB) and caffeine-bilosomes (CB) that could non-invasively target and deposit in fat cells. RSV bilosomes (RB) were prepared as a non-targeted system for comparison. CRB showed nanosize (364.1 nm ±6.5 nm) and high entrapment for both active compounds. Rats treated topically with CRB revealed a significant decrease (P = 0.039) in body weight. Histological analysis of the excised skin demonstrated a reduction in the subcutaneous fatty layer thickness and a decrease in the size of connective tissue-imbedded fat cells. Kidney histological examination of RB-treated rats showed subcapsular tubular epithelial cells with cytoplasmic vacuolation. This reflects a systemic effect of RSV from the non-targeted RB compared to CRB, which had a targeting effect on the adipose tissue. In conclusion, CAF in CRB significantly enhanced RSV deposition in adipose tissue and assisted its local-acting effect for managing obesity and cellulite.

Recent Advances in Long-Acting Drug Delivery and Formulations.

Conventional immediate-release delivery systems are simple, industrially reproducible, acceptable, and easy-to-use by most patients [...].

Comparative Investigation into the Roles of Imipenem:Cyclodextrin Complexation and Antibiotic Combination in Combatting Antimicrobial Resistance in Gram-Negative Bacteria.

Extensively drug-resistant (XDR), multidrug-resistant (MDR) and pandrug-resistant (PDR) Gram-negative microorganisms (GNBs) are considered a significant global threat. ß-lactam and aminoglycoside combinations and imipenem:cyclodextrin inclusion complexes were studied for the treatment of lethal GNBs. This is because of the broad empiric coverage of the two drugs and their possession of different spectra of activity. Two cyclodextrins (ß- and hydroxy propyl ß-cyclodextrins) were utilized for inclusion complex formation with imipenem using the physical and kneading methods. In silico investigation using the molecular docking and Fourier-infrared spectroscopy (FTIR) were employed to estimate binding constant and confirm complex formation, respectively. The in vitro effects of amikacin and imipenem combination in comparison to the effect of imipenem-ß- and hydroxy propyl ß-cyclodextrin (CD) complexes against Klebsiella spp. and Acinetobacter baumannii were studied. The isolated microorganisms' antimicrobial responsiveness to various antibiotics (19 antibiotics) was evaluated. It was found that piperacillin/tazobactam and gentamycin (resistance rates were 33.3% and 34%, respectively) were the most effective antimicrobials. The in vitro studies have been performed by the checkerboard technique and time-killing assay. The studied combination of amikacin and imipenem showed a substantial drop in bacterial count (p < 0.05). The in vitro studies demonstrated a synergism for the investigated combination. Conventional PCR was used in molecular studies to identify the resistance genes bla IMP and aac (6')-Ib. The blaIMP and aac (6')-Ib were recorded in 38.2% and 3.6% of the studied isolates, respectively. The in vitro studies showed synergistic effects among the tested antibiotics with FICIs of ≤0.5. Finally, the study compared the reduction in bacterial count between the tested antibiotic combinations and imipenem:CD physical and kneaded mixtures. Imipenem:CD inclusion complexes demonstrated a significant bacterial count reduction over the antibiotic combination. These results highlight the emerging role of CDs as safe biofunctional excipients in the combat against superbug bacterial resistance.

Characterization and Bio-Evaluation of the Synergistic Effect of Simvastatin and Folic Acid as Wound Dressings on the Healing Process.

Wound healing is a significant healthcare problem that decreases the patient's quality of life. Hence, several agents and approaches have been widely used to help accelerate wound healing. The challenge is to search for a topical delivery system that could supply long-acting effects, accurate doses, and rapid healing activity. Topical forms of simvastatin (SMV) are beneficial in wound care. This study aimed to develop a novel topical chitosan-based platform of SMV with folic acid (FA) for wound healing. Moreover, the synergistic effect of combinations was determined in an excisional wound model in rats. The prepared SMV-FA-loaded films (SMV-FAPFs) were examined for their physicochemical characterizations and morphology. Box-Behnken Design and response surface methodology were used to evaluate the tensile strength and release characteristics of the prepared SMV-FAPFs. Additionally, Fourier transform infrared (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction pattern (XRD), and animal studies were also investigated. The developed SMV-FAPFs showed a contraction of up to 80% decrease in the wound size after ten days. The results of the quantitative real-time polymerase chain reaction (RT-PCR) analysis demonstrated a significant upregulation of dermal collagen type I (CoTI) expression and downregulation of the inflammatory JAK3 expression in wounds treated with SMV-FAPFs when compared to control samples and individual drug treatments. In summary, it can be concluded that the utilization of SMV-FAPFs holds great potential for facilitating efficient and expeditious wound healing, hence presenting a feasible substitute for conventional topical administration methods.

Preformulation-Assisted Design of Ketorolac Tromethamine for Effective Ophthalmic Delivery.

Background: The eye is a highly protected organ from ocularly administered drugs; drug- and formulation-related factors contribute significantly to ocular bioavailability. There has been a growing interest in using nonsteroidal anti-inflammatory drugs in ophthalmology for treating postoperative pain, inflammation, and seasonal allergic conjunctivitis. A preformulation-assisted design boosts efficacy and reduces dose requirements. Methods: This work aims to study the preformulation characteristics of ketorolac tromethamine to improve ocular performance and future formulation development through developing an high-performance liquid chromatography (HPLC) stability-indicating assay, forced degradation under stress conditions, solubility, as well as partition and distribution coefficient measurements. An isocratic HPLC with diode array detector method was developed and validated. Accelerated degradation under different stressors (acid, alkali, heat, and oxidative) was studied. In addition, solubility, partition, and distribution were investigated at different pHs of 3.5-7.4. Results: The results indicated that the developed HPLC method was simple, rapid (retention time ≃3 min), sensitive, selective, robust, and stability indicating. The drug seems more chemically sensitive to acid degradation (∼30% and 40% of the drug was degraded under 0.1 M and 1 M HCl at 60°C for 24 h, respectively). Another significant degradation was recorded in the following order: Oxidative > alkali > heat (phosphate-buffered saline) > heat (distilled water). Being a weak ionizable drug, both water and lipid solubility, as measured through partition coefficients, it demonstrated pH-dependency. Conclusion: For the optimum balance of water and lipid solubility required for penetration through the lipophilic corneal epithelial barrier, ketorolac eye drops would be better formulated between pH 5.5 and 6.6 than being formulated at the physiological fluid pH 7.4, where the drug is extremely hydrophilic and less permeable.

Formulation and optimization of lipid- and Poloxamer-tagged niosomes for dermal delivery of terbinafine: preparation, evaluation, and in vitro antifungal activity.

Fungal skin diseases are recognized as a global burden disease that affect human quality adjusted life. Terbinafine belongs to allylamine and broad-spectrum antifungal drugs but considered practically insoluble. Different lipids/surfactant with two different molar ratios were investigated with Span 40-based niosomes; characterized for size, morphology, loading capacity (EE%), in vitro release, kinetics, and antifungal activities. Vesicle sizes (0.19-1.23 µm), EE% (25-99%), zeta potential (> -32 mV), and in vitro release rates were dependent on both lipid types and ratios. Higher ratios of Poloxamer 407 preferably formed mixed micelles rather than forming noisome bilayers. Both Compritol and Precirol were deemed to be potential alternatives to cholesterol as bilayer membrane stabilizers. Terbinafine-loaded Compritol and Precirol stabilized niosomes were successfully prepared and demonstrated superior antifungal activities in vitro (inhibition zones) using Candida albicans ATCC 60913.

Chitosan/Solid-Lipid Nanoparticles Hybrid Gels for Vaginal Delivery of Estradiol for Management of Vaginal Menopausal Symptoms.

Hormonal replacement therapy is the mainstay treatment to improve quality of life and reduce mortality. With the increasing number of young women with early menopause, women now live longer (increased life expectancy). However, poor patient compliance with oral estrogen therapy has emerged. Intravaginal estrogen therapy can provide significant benefits with minimal risk for postmenopausal women with symptoms of the lower urinary tract and vaginal area but who do not want to take oral estrogen. In this study, estradiol-loaded solid lipid nanoparticles (SLPs) were prepared from compritol ATO 888 and precirol ATO 5, and two different stabilizers (Pluronic F127 and Tween 80) were studied. Selected SLPs (F3 and F6) were coated with different concentrations of the mucoadhesive and sustained-release polymer chitosan. Furthermore, gelation time, viscosity, mucoadhesion, ex vivo permeation, and in vitro irritation for vaginal irritation were studied. Particle sizes ranged between 450-850 nm, and EE% recorded 50-83% for the six SLPs depending on the type and amount of lipids used. Cumulative % drug release was significantly enhanced and was recorded at 51% to 83%, compared to that (less than 20%) for the control suspension of estradiol. Furthermore, extensive thermal gelation and mucoadhesion were recorded for chitosan-coated SLPs. Up to 2.2-fold increases in the permeation parameters for SLPs gels compared to the control suspension gel were recorded, revealing a slight to moderate irritation on Hela cell lines. These findings demonstrated chitosan-coated estradiol SLPs as novel and promising vaginal mucoadhesive hybrid nanogels.

Captopril Polyvinyl Alcohol/Sodium Alginate/Gelatin-Based Oral Dispersible Films (ODFs) with Modified Release and Advanced Oral Bioavailability for the Treatment of Pediatric Hypertension.

Hypertension can begin in childhood; elevated blood pressure in children is known as pediatric hypertension. Contrary to adult hypertension, there is a scarcity of commercial medications suitable for the treatment of pediatric hypertension. The aim of this study was to develop orally dispersible films (ODFs) loaded with captopril for the treatment of hypertension in children. Captopril-loaded ODFs were composed of different blends of synthetic polymers, such as polyvinyl alcohol (PVA) and polyvinyl pyrrolidone, and natural polymers, such as sodium alginate (SA) and gelatin. The ODFs were characterized based on their mechanical and thermal properties, drug content, surface morphology, in vitro disintegration, in vitro release, and bioavailability. A novel HPLC method with precolumn derivatization was developed to precisely and selectively determine captopril levels in plasma. A low concentration of PVA and a high concentration of SA generated ODFs with faster hydration and disintegration rates. SA-based films exhibited fast disintegration properties (1-2 min). The optimized modified-release film (F2) showed significant (p < 0.05) enhancement in bioavailability (AUC = 1000 ng min/mL), with a value 1.43 times that of Capoten® tablets (701 ng min/mL). While the plasma concentration peaking was in favor of the immediate-release tablet, Tmax was significantly prolonged by 5.4 times for the optimized ODF (3.59 h) compared with that of the tablets (0.66 h). These findings indicate uniform and sustained plasma concentrations, as opposed to the pulsatile and rapid plasma peaking of captopril from the immediate-release tablets. These findings suggest that the modified release of oral films could offer more favorable plasma profiles and better control of hypertension than the conventional release tablets.

Proniosomal Gel-Loaded Phosphodiesterase Inhibitors (Sildenafil, Vardenafil, and Tadalafil): Prospects for Topical Penile Therapy of Tadalafil for Treatment of Erectile Dysfunction.

Oral phosphodiesterase inhibitors have emerged as a game changer for the treatment of erectile dysfunction (ED) since attaining FDA approval for its first member, sildenafil, in 1998. Topical penile therapy could be a viable replacement for oral medication that would transform the treatment of ED for many decades to come. This innovative idea could offer a safer topical alternative with less vision and cardiovascular side effects than the oral route. This work aims at developing proniosomal gels for three selected members (sildenafil, vardenafil, and tadalafil) and investigating the proniosomal gels on a rodent model. Niosomes derived from the parent proniosomal gels were characterized for entrapment efficiency (EE%), size, polydispersity index (PDI), zeta potential, and morphology. Proniosomal gels were evaluated for skin permeation, in vivo mating behaviors, and biochemical assays of nitric oxide (NO) and cyclic guanosine monophosphate (cGMP) post penile topical administrations. The optimized proniosomes loaded with tadalafil (F1-T) were compared with oral tablets (Cialis®). Proniosomal gels demonstrated significant enhancement of skin penetration by up to 5.5-fold, compared to control topical suspension. Tadalafil-loaded proniosomes showed superior skin permeability over sildenafil- and vardenafil-loaded proniosomes. In addition, significant improvement was noticed regarding intromission number, intromission ratio, NO, and cGMP for the proniosomal gel F1-T, compared to the untreated control. No statistically significant (p > 0.05) differences in sexual performance or biochemical parameters (NO and cGMP levels) were recorded among orally and topically (tadalafil proniosomal gel) administered groups. These findings support tadalafil topical penile therapy as a promising alternative to the oral route.

Formulation and In-Vitro/Ex-Vivo Characterization of Pregelled Hybrid Alginate-Chitosan Microparticles for Ocular Delivery of Ketorolac Tromethamine.

Innovative hybrid chitosan-sodium alginate (Ch-Ag) microparticles (MPs) were fabricated using both the ionic gelation method as well as the pre-gelation technique. The hybrid Ch-Ag MPs were studied for size, zeta potential, morphology, mucoadhesion, in-vitro release, corneal permeation, and ocular irritation using lens and corneal epithelial cell lines. The average particle size ranged from 1322 nm to 396 nm. The zeta potential for the prepared formulations showed an increase with increasing Ch concentrations up to a value of >35 mV; the polydispersity index (PDI) of some optimized MPs was around 0.1. Compared to drug-free MPs, ketorolac-loaded Ch-Ag MPs demonstrated a drug proportion-dependent increase in their size. SEM, as well as TEM of KT-loaded MPs, confirmed that the formed particles were quasi-spherical to elliptical in shape. The KT release from the MPs demonstrated a prolonged release profile in comparison to the control KT solution. Further, mucoadhesion studies with porcine mucin revealed that the KT-loaded MPs had effective mucoadhesive properties, and polymeric particles were stable in the presence of mucin. Corneal permeation was studied on bovine eyes, and the results revealed that Ch-based MPs were capable of showing more sustained KT release across the cornea compared with that for the control drug solution. Conclusively, the cytotoxicity assay confirmed that the investigated MPs were non-irritant and could confer protection from direct drug irritation of KT on the ocular surface. The MTT cytotoxicity assay confirmed that KT-loaded MPs showed acceptable and reasonable tolerability with both human lens and corneal epithelial cell lines compared to the control samples.

Recent Advances of Ocular Drug Delivery Systems: Prominence of Ocular Implants for Chronic Eye Diseases.

Chronic ocular diseases can seriously impact the eyes and could potentially result in blindness or serious vision loss. According to the most recent data from the WHO, there are more than 2 billion visually impaired people in the world. Therefore, it is pivotal to develop more sophisticated, long-acting drug delivery systems/devices to treat chronic eye conditions. This review covers several drug delivery nanocarriers that can control chronic eye disorders non-invasively. However, most of the developed nanocarriers are still in preclinical or clinical stages. Long-acting drug delivery systems, such as inserts and implants, constitute the majority of the clinically used methods for the treatment of chronic eye diseases due to their steady state release, persistent therapeutic activity, and ability to bypass most ocular barriers. However, implants are considered invasive drug delivery technologies, especially those that are nonbiodegradable. Furthermore, in vitro characterization approaches, although useful, are limited in mimicking or truly representing the in vivo environment. This review focuses on long-acting drug delivery systems (LADDS), particularly implantable drug delivery systems (IDDS), their formulation, methods of characterization, and clinical application for the treatment of eye diseases.

Exploration of the Safety and Solubilization, Dissolution, Analgesic Effects of Common Basic Excipients on the NSAID Drug Ketoprofen.

Since its introduction to the market in the 1970s, ketoprofen has been widely used due to its high efficacy in moderate pain management. However, its poor solubility and ulcer side effects have diminished its popularity. This study prepared forms of ketoprofen modified with three basic excipients: tris, L-lysine, and L-arginine, and investigated their ability to improve water solubility and reduce ulcerogenic potential. The complexation/salt formation of ketoprofen and the basic excipients was prepared using physical mixing and coprecipitation methods. The prepared mixtures were studied for solubility, docking, dissolution, differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), in vivo evaluation for efficacy (the writhing test), and safety (ulcerogenic liability). Phase solubility diagrams were constructed, and a linear solubility (AL type) curve was obtained with tris. Docking studies suggested a possible salt formation with L-arginine using Hirshfeld surface analysis. The order of enhancement of solubility and dissolution rates was as follows: L-arginine > L-lysine > tris. In vivo analgesic evaluation indicated a significant enhancement of the onset of action of analgesic activities for the three basic excipients. However, safety and gastric protection indicated that both ketoprofen arginine and ketoprofen lysine salts were more favorable than ketoprofen tris.

Design, Preparation and Evaluation of Supramolecular Complexes with Curcumin for Enhanced Cytotoxicity in Breast Cancer Cell Lines.

Curcumin is one of the most researched phytochemicals by pharmacologists and formulation scientists to unleash its potential therapeutic benefits and tackle inherent biopharmaceutic problems. In this study, the native ß-cyclodextrin (CD) and three derivatives, namely, Captisol (sulfobutyl ether ß-CD), hydroxypropyl ß-cyclodextrin, and hydroxyethyl ß-cyclodextrin were investigated for inclusion complexes with curcumin using two preparation methods (physical mixing and solvent evaporation). The prepared complexes were studied for docking, solubility, FTIR, DSC, XRD, and dissolution rates. The best-fitting curcumin: cyclodextrins (the latter of the two CDs) were evaluated for cytotoxicity using human breast cell lines (MCF-7). Dose-dependent cytotoxicity was recorded as IC50% for curcumin, curcumin: hydroxyethyl ß-cyclodextrin, and curcumin: hydroxypropyl ß-cyclodextrin were 7.33, 7.28, and 19.05 µg/mL, respectively. These research findings indicate a protective role for the curcumin: hydroxypropyl ß-cyclodextrin complex on the direct cell lines of MCF-7.

Glycation-induced age-related illnesses, antiglycation and drug delivery strategies.

OBJECTIVES: Ageing is a major cause of multiple age-related diseases. Several mechanisms have been reported to contribute to these abnormalities including glycation, oxidative stress, the polyol pathway and osmotic stress. Glycation, unlike glycosylation, is an irregular biochemical reaction to the formation of active advanced glycation end-products (AGEs), which are considered to be one of the causes of these chronic diseases. This study provides a recent and comprehensive review on the possible causes, mechanisms, types, analytical techniques, diseases and treatments of the toxic glycation end products. KEY FINDINGS: Several mechanisms have been found to play a role in generating hyperglycaemia-induced oxidative stress including an increase in the levels of reactive oxygen species (ROS), increase in the levels of AGEs, binding of AGEs and their receptors (RAGE) and the polyol pathway and thus have been investigated as promising novel targets. SUMMARY: This review focuses on the key mechanisms attributed to cumulative increases of glycation and pathological RAGE expression as a significant cause of multiple age-related diseases, and reporting on different aspects of antiglycation therapy as a novel approach to managing/treating age-related diseases. Additionally, historical, current and possible future antiglycation approaches will be presented focussing on novel drug delivery methods.

Vardenafil Oral Dispersible Films (ODFs) with Advanced Dissolution, Palatability, and Bioavailability.

Oral, quick response, and on demand, also known as a spontaneous oral treatment for erectile dysfunction, is highly needed by both patients and physicians. Vardenafil is selective (fewer side effects) and more effective in difficult-to-treat conditions than sildenafil. This study aims at fostering the dual objectives of using biomolecules such as artificial sweetening agents to solubilize and mask the bitterness of vardenafil loaded on biodegradable polymeric materials (PVA, MC, SA, and PVP K30) to fabricate oral, fast-dissolving films (vardenafil ODFs) in the mouth without the need for water to ingest the dosage form. Furthermore, coprecipitated-dispersed mixtures of vardenafil and three sweeteners (sorbitol, acesulfame K, and sucralose) were prepared and characterized using FTIR, DSC, and solubility studies. Moreover, eight different vardenafil ODFs were prepared using the solvent-casting method. Modified gustatory sensation test, in vitro disintegration, and release studies were performed. In addition, the optimized ODF (F8) was compared with the commercial film-coated tablets pharmacokinetically (relative bioavailability, onset, and duration of actions were estimated). The results indicated that the three sweetening agents had comparable solubilizing capacity. However, both sucralose- and acesulfame K-based ODFs have a more enhanced sweet and palatable taste than sorbitol-sweetened ODF. The SA- and PVP K30-based ODFs showed significantly faster disintegration times and release rates than MC. In conclusion, PVA has good film-forming properties, but a higher ratio of PVA adversely affected the disintegration and release characteristics. The % relative bioavailability for ODF was 126.5%, with a superior absorption rate constant (Ka) of 1.2-fold. The Cmax and estimated Tmax were compared to conventional film-coated tablets.

Using Bio-Layer Interferometry to Evaluate Anti-PEG Antibody-Mediated Complement Activation.

The purpose of this study was to develop a Bio-layer interferometry (BLI) system that could be an alternative approach for the direct evaluation of anti-polyethylene glycol (PEG) immunoglobulin M (IgM)-mediated complement activation of the accelerated blood clearance (ABC) phenomenon. Complement activation is well known to play an important role in the clearance of PEGylated and non-PEGylated nanomedicines following intravenous injection. This complement system is also thought to be responsible for the ABC phenomenon wherein repeated injections of PEGylated products are bound by anti-PEG antibodies. This study used three different sources of anti-PEG antibodies: HIK-M09 monoclonal antibodies (mAbs); HIK-M11 mAbs; and antiserum containing polyclonal anti-PEG IgMs. 1,2-Distearoyl-sn-glycero-3-phosphoethanolamine-n-[methoxy (polyethylene glycol)-2000] (mPEG2000-DSPE) was immobilized as an antigen on aminopropyl silane biosensor chips of BLI. All anti-PEG IgMs in the sources increased the signals (thickness of the layer around the sensor tip) regarding binding of anti-PEG antibodies to PEG on the chips. In all anti-PEG IgM sources, further increases in the signals were observed when incubated in naïve mouse serum, which is a complement source, but not in heat inactivated (56 °C, 30 min) mouse serum, which abolishes complement activity. These findings show that the complement activation mediated via anti-PEG IgMs, which occurred on the sensor chips, was detected via BLI analysis. The complement activation induced by all anti-PEG IgM sources was confirmed via conventional enzyme-linked immunosorbent assay (ELISA), which is the conventional mode for detection of complement activation. Our study results show that BLI is a simple alternative method for the detection of complement activation.

Hybrid thermosensitive-mucoadhesive in situ forming gels for enhanced corneal wound healing effect of L-carnosine.

PURPOSE: Thermosensitive in situ gels have been around for decades but only a few have been translated into ophthalmic pharmaceuticals. The aim of this study was to combine the thermo-gelling polymer poloxamer 407 and mucoadhesive polymers chitosan (CS) and methyl cellulose (MC) for developing effective and long-acting ophthalmic delivery systems for L-carnosine (a natural dipeptide drug) for corneal wound healing. METHODS: The effect of different polymer combinations on parameters like gelation time and temperature, rheological properties, texture, spreading coefficients, mucoadhesion, conjunctival irritation potential, in vitro release, and ex vivo permeation were studied. Healing of corneal epithelium ulcers was investigated in a rabbit's eye model. RESULTS: Both gelation time and temperature were significantly dependent on the concentrations of poloxamer 407 and additive polymers (chitosan and methyl cellulose), where it ranged from <10 s to several minutes. Mechanical properties investigated through texture analysis (hardness, adhesiveness, and cohesiveness) were dependent on composition. Promising spreading-ability, mucoadhesion, transcorneal permeation of L-carnosine, high ocular tolerability, and enhanced corneal epithelium wound healing were recorded for poloxamer 407/chitosan systems. CONCLUSION: In situ gelling systems comprising combinations of poloxamer-chitosan exhibited superior gelation time and temperature, mucoadhesion, and rheological characteristics suitable for effective long-acting drug delivery systems for corneal wounds.

Polymeric/Dextran Wafer Dressings as Promising Long-Acting Delivery Systems for Curcumin Topical Delivery and Enhancing Wound Healing in Male Wistar Albino Rats.

Curcumin is the main active constituent in turmeric, and it is one of the biopolyphenolic compounds. A cumulative body of research supports the use of curcumin in the treatment of wounds, yet poor water solubility and lack of therapeutic dose determination hamper its use for this therapeutic purpose. This work aimed at preparing novel curcumin wafer dressings to provide a favorable environment for wound healing. Hybrid synthetic (PVA, PVP, HPMC, and CMC) and biodegradable (sodium alginate and dextran) polymers were employed to prepare wafer dressings loaded with incremental three doses (2, 10, and 20 mg) of curcumin per a wafer dressing. The solvent casting method was used to prepare the dressings. Dimension, surface pH, mechanical properties, DSC, FTIR, XRD, erosion time, and in vitro release were studied. Skin wound healing assay was studied in Wistar albino rats. Six curcumin-loaded wafers were successfully prepared with good mechanical properties. Curcumin was dispersed in an amorphous/molecular form, as evidenced by thermal (DSC) and spectral (FTIR and XRD) analyses. Prolonged curcumin release (>24 h) was recorded for F6 (10 mg curcumin) and F7 (20 mg curcumin). Wound healing rate constants and time for 50% wound closure (T1/2) were estimated from a semi-log wound diameter versus time curve. A superior healing rate (up to 3-fold faster) was recorded for curcumin-loaded wafer dressings containing 10 mg (F6) with T1/2 of 7 days compared to 20 days for the placebo-treated group. These results warrant using the selected curcumin-loaded wafer dressing for safer and faster wound closure.

A Novel Curcumin Arginine Salt: A Solution for Poor Solubility and Potential Anticancer Activities.

Curcumin is a natural polyphenolic compound with well-known anticancer properties. Poor solubility and permeability hamper its use as an anticancer pharmaceutical product. In this study, L-arginine, a basic amino acid and a small hydrophilic molecule, was utilized to form a salt with the weak acid curcumin to enhance its solubility and potentiate the anticancer activities of curcumin. Two methods were adopted for the preparation of curcumin: L-arginine salt, namely, physical mixing and coprecipitation. The ion pair or salt was characterized for docking, solubility, DSC, FTIR, XRD, in vitro dissolution, and anticancer activities using MCF7 cell lines. The molecular docking suggested a salt/ion-pair complex between curcumin and L-arginine. Curcumin solubility was increased 335- and 440-fold by curcumin in L-arginine, physical, and co-precipitated mixtures, respectively. Thermal and spectral analyses supported the molecular docking and formation of a salt/ion pair between curcumin and L-arginine. The cytotoxicity of curcumin L-arginine salt significantly improved (p < 0.05) by 1.4-fold, as evidenced by the calculated IC50%, which was comparable to Taxol (the standard anticancer drug but with common side effects).

Polymeric long-acting drug delivery systems (LADDS) for treatment of chronic diseases: Inserts, patches, wafers, and implants.

Non-oral long-acting drug delivery systems (LADDS) encompass a range of technologies for precisely delivering drug molecules into target tissues either through the systemic circulation or via localized injections for treating chronic diseases like diabetes, cancer, and brain disorders as well as for age-related eye diseases. LADDS have been shown to prolong drug release from 24 h up to 3 years depending on characteristics of the drug and delivery system. LADDS can offer potentially safer, more effective, and patient friendly treatment options compared to more invasive modes of drug administration such as repeated injections or minor surgical intervention. Whilst there is no single technology or definition that can comprehensively embrace LADDS; for the purposes of this review, these systems include solid implants, inserts, transdermal patches, wafers and in situ forming delivery systems. This review covers common chronic illnesses, where candidate drugs have been incorporated into LADDS, examples of marketed long-acting pharmaceuticals, as well as newly emerging technologies, used in the fabrication of LADDS.