Hyaluronic acid/alginate-based biomimetic hydrogel membranes for accelerated diabetic wound repair.

The study aims to develop a new multifunctional biopolymer-based hydrogel membrane dressing by adopting a solvent casting method for the controlled release of cefotaxime sodium at the wound site. Sodium alginate enhances collagen production in the skin, which provides tensile strength to healing tissue. Moreover, the significance of extracellular molecules such as hyaluronic acid in the wound the healing cascade renders these biopolymers an essential ingredient for the fabrication of hydrogel membranes via physical crosslinking (hydrogen bonding). These membranes were further investigated in terms of their structure, and surface morphology, as well as cell viability analysis. A membrane with the most suitable characteristics was chosen as a candidate for cefotaxime sodium loading and in vivo analysis. Results show that the 3D porous nature of developed membranes allows optimum water vapor and oxygen transmission (>8.21 mg/mL) to divert excessive wound exudate away from the diabetic wound bed, MTT assay confirmed cell viability at more than 80%. In vivo results confirmed that the CTX-HA-Alg-PVA hydrogel group showed rapid wound healing with accelerated re-epithelization and a decreased inflammatory response. Conclusively, these findings indicate that CTX-HA-Alg-PVA hydrogel membranes exhibit a suitable niche for use as dressing membranes for healing of diabetic wounds.

Folic acid-decorated alginate nanoparticles loaded hydrogel for the oral delivery of diferourylmethane in colorectal cancer.

The disease-related suffering in colorectal cancer remains prevalent despite advancements in the field of drug delivery. Chemotherapy-related side effects and non-specificity remain a challenge in drug delivery. The great majority of hydrophobic drugs cannot be successfully delivered to the colon orally mainly due to poor solubility, low bioavailability, pH differences, and food interactions. Polymeric nanoparticles are potential drug delivery candidates but there are numerous limitations to their usefulness in colon cancer. The nanoparticles are removed from the body rapidly by p-glycoprotein efflux, inactivation, or breakdown by enzymes limiting their efficiency. Furthermore, there is a lack of selectivity in targeting cancer cells; nanoparticles may also target healthy cells, resulting in toxicity and adverse effects. The study aimed to use nanoparticles for specific targeting of the colorectal tumor cells via the oral route of administration without adverse effects. Folic acid (FA), a cancer-targeting ligand possessing a high affinity for folate receptors overexpressed in colorectal cancers was conjugated to sodium alginate- nanoparticles by NH2-linkage. The folic-acid conjugated nanoparticles (FNPs) were delivered to the colon by a pH-sensitive hydrogel synthesized by the free radical polymerization method to provide sustained drug release. The developed system referred to as the "Hydrogel-Nano (HN) drug delivery system," was specifically capable of delivering diferourylmethane to the colon. The HN system was characterized by DLS, FTIR, XRD, TGA, DSC, and SEM. The FNPs size, polydispersity index, and zeta potential were measured. The folic acid-conjugation to nanoparticles' surface was studied by UV-visible spectroscopy using Beer-Lambert's law. In-vitro studies, including sol-gel, porosity, drug loading, entrapment efficiency, etc., revealed promising results. The swelling and release studies showed pH-dependent release of the drug in colonic pH 7.4. Cellular uptake and cytotoxicity studies performed on FR-overexpressed Hela cell lines and FR-negative A-549 cell lines showed facilitated uptake of nanoparticles by folate receptors. A threefold increase in Cmax and prolongation of the mean residence time (MRT) to 14.52 +/- 0.217 h indicated sustained drug release by the HN system. The findings of the study can provide a sufficient ground that the synergistic approach of the HN system can deliver hydrophobic drugs to colorectal cancer cells via the oral route, but further in-vivo animal cancer model studies are required.

Polyvinylpyrrolidone K-30-Based Crosslinked Fast Swelling Nanogels: An Impeccable Approach for Drug's Solubility Improvement.

Poor solubility is a global issue of copious pharmaceutical industries as large number of drugs in development stage as well as already marketed products are poorly soluble which results in low dissolution and ultimately dosage increase. Current study is aimed at developing a polyvinylpyrrolidone- (PVP-K30-) based nanogel delivery system for solubility enhancement of poorly soluble drug olanzapine (OLP), as solubilization enhancement is the most noteworthy application of nanosystems. Crosslinking polymerization with subsequent condensation technique was used for the synthesis of nanogels, a highly responsive polymeric networks in drug's solubility. Developed nanogels were characterized by percent entrapment efficiency, sol-gel, percent swelling, percent drug loaded content (%DLC), percent porosity, stability, solubility, in vitro dissolution studies, FTIR, XRD, and SEM analysis. Furthermore, cytotoxicity study was conducted on rabbits to check the biocompatibility of the system. Particle size of nanogels was found with 178.99 ± 15.32 nm, and in vitro dissolution study exhibited that drug release properties were considerably enhanced as compared to the marketed formulation OLANZIA. The solubility studies indicated that solubility of OLP was noticeably improved up to 36.7-fold in phosphate buffer of pH 6.8. In vivo cytotoxicity study indicated that prepared PVP-K30-based formulation was biocompatible. On the basis of results obtained, the developed PVP-K30-co-poly (AMPS) nanogel delivery system is expected to be safe, effective, and cost-effective for solubility improvement of poorly soluble drugs.

Synthesis of PEG-4000-co-poly (AMPS) nanogels by cross-linking polymerization as highly responsive networks for enhancement in meloxicam solubility.

Poor solubility is an ongoing issue and the graph of poorly soluble drugs has increased markedly which critically affect their dissolution, bioavailability, and clinical effects. This common issue needs to be addressed, for this purpose a series of polyethylene glycol (PEG-4000) based nanogels were developed by free radical polymerization technique to enhance the solubility, dissolution, and bioavailability of poorly soluble drug meloxicam (MLX), as improved solubility is the significant application of nanosystems. Developed nanogels formulations were characterized by FTIR, XRD, SEM, zeta sizer, percent equilibrium swelling, drug loaded content (DLC), drug entrapment efficiency (DEE), solubility studies, and in vitro dissolution studies. Furthermore, cytotoxicity studies were conducted in order to determine the bio-compatibility of the nanogels drug delivery system to biological environment. Nanogels particle size was found to be 156.19 ± 09.33 d.nm. Solubility study confirmed that the solubility of poorly soluble drug MLX was significantly enhanced up to 36 folds as compared to reference product (Mobic®). The toxicity study conducted on rabbits and MTT assay endorsed the safety of the developed nanogels formulations to the biological system.

Design and development of lipid modified chitosan containing muco-adhesive self-emulsifying drug delivery systems for cefixime oral delivery.

Current study was aimed to design and develop muco-adhesive self-nano emulsifying drug delivery system (SNEDDs) for improved pharmacokinetics of Cefixime (CFX) in rabbits. The components of SNEDDs formulation i.e., cinnamon oil, Tween® 80, and PEG 200 as oil, surfactant, and co-surfactant respectively were selected based on their high solubilizing capability of the drug. SNEDDs formulation was optimized using Design of experiments (D-optimal design) in terms of droplet size, poly dispersity index and zeta potential. The optimized SNEDDs formulation was studied for various parameters like droplet size, morphology, zeta potential, emulsification, optical clarity, thermodynamic stability, GIT stability, and robustness to dilution. CFX was loaded to optimized formulation to form CFX-SNEDDs. Furthermore, acyl-chitosan, a muco-adhesive agent, was added to CFX-SNEDDS to prepare CHT-CFX-SNEDDS. In vitro drug release showed the controlled release behavior reached a maximum value of 70 % at pH 6.8 within 24 h. The droplet size, atomic force microscopy, and optical clarity analysis revealed the formation of nanosized emulsion (156 ± 25 nm) with spherical morphology. Also in vivo pharmacokinetic studies on rabbits showed an increased drug plasma concentration for CHT-CFX-SNEDDs (15 ± 3 µg/mL) and CFX-SNEDDs (9 ± 2 µg/mL) in comparison with control CFX (4 ± 1 µg/mL). The results indicated that the developed CHT-CFX-SNEDDs with an increased degree of solubilization, permeation, and nanosized range emulsion enhance the oral performance of CFX.

Awareness and Attitudes of the Pakistani Population With Regard to Physician-Pharmaceutical Company Interaction: A Cross-Sectional Study.

Objective: To determine the awareness and attitudes of the Pakistani population regarding physician-pharmaceutical company interactions. Methods: The data were collected from primary health care clinics and pharmacy outlets located within cities of six randomly selected districts of the Punjab Province. Those individuals (age ≥18 years) who have just completed their visit to the physician and well understand Urdu language were approached. Descriptive analysis was performed for all variables by using SPSS (IBM version 26). Results: A total of 3,852 participants fully completed the study out of 4,301 (response rate 89.5%). Of those, 30.9% were female; two-thirds (66.7%) were aware of drug representatives' visits to clinics. The majority were aware of pharmaceutical company material presence (or absence) in the physicians' rooms (56.6%), company items with logos (66.8%), patient education materials (73.4%), and 60.8% thought that receiving gifts from companies was "wrong/unethical" practice for physicians, which was lower in comparison to other professions such as judges to accept gifts from lawyers (65.6%) and professional sports umpires to acknowledge gifts (64.3%). A minority said that they have lower trust on physicians for using drug company notepads or pens (16.7%), going on trips sponsored by the company (16.7%), accepting gifts <15,000 PKR (90.3 US$) (26.7%), and accepting gifts >15,000 PKR (90.3 US$) (40.0%). Conclusion: Survey participants were well aware of physician-pharmaceutical company interactions. Participants were more knowledgeable regarding the pharmaceutical company presence (or absence) in physicians' offices than about gift-related practices of physicians. Trust on the physician was not affected by small gifts but by the large gifts.

Bioinspired sodium alginate based thermosensitive hydrogel membranes for accelerated wound healing.

Despite substantial progress made in the development of wound dressings, wound management remains a great challenge, which compels significant burden to the patient and healthcare system. Owing to its intricate pathophysiology particularly, wounds with bacterial burden impose substantial challenges to the conventional wound dressings, and hence, demands development of novel and more efficient wound healing modalities. Therefore, the aim of the present study was to design a novel thermosensitive hydrogel membrane composed of sodium alginate, poloxamer 407, pluronic F-127, and polyvinyl alcohol for accelerated wound healing. The developed hydrogel membranes were evaluated using 1HNMR, FTIR, SEM, XRD, TGA and DSC for sufficient cross-linking, surface morphology, tensile strength, mechanical properties, thermos-sensitivity and thermal stability. Moreover, the swelling properties, drug release behavior, gel fraction, water vapor transmission rate, and antibacterial proficiency of the developed hydrogel membrane were also investigated. The resulting analysis revealed that developed hydrogel membranes exhibited good mechanical properties and tensile strength to withstand the external frictional stress while covering the wound, exceptional swelling properties and surface porosity for sustained release of encapsulated drug (amikacin). Antibacterial results showed that amikacin-loaded hydrogel membranes exhibited significantly higher zone of inhibition against S. aureus and P. aregnosa. In accordance with our hypothesis, excisional animal model showed significantly higher wound healing efficacy of hydrogel membranes in terms of faster wound closure, greater re-epithelization, and granulation tissue formation compared with positive and negative control groups. Conclusively, the extensive evaluations clearly evidenced a promising wound healing potential of our novel alginate-based hydrogel membrane as an efficient wound healer for faster wound healing.

Effect of an Al/Mg Hydroxide Antacid and Food on the Pharmacokinetics of Dexibuprofen.

OBJECTIVES: In this communication we report an important findings, the effect of Al/Mg hydroxide antacid and food on the pharmacokinetics of dexibuprofen when administered concomitantly. METHODS: Subjects were divided into four groups, each containing 6 subjects, to evaluate the effect of antacid and food on pharmacokinetic of dexibuprofen. A new HPLC method was developed and validated for plasma sample analysis. Mobile phase was comprised of Acetonitrile: Methanol: 0.05M Phosphate buffer (40:10:50), pH was adjusted to 6.85±0.01 with NaOH. Mobile phase was eluted through C18-ODS column and drug was detected at 223 nm. Plasma was obtained and stored at - 70°C until analysis. Drug was extracted from each plasma sample of volunteer and quantified by using HPLC technique. RESULTS: A decrease in dexibuprofen absorption was observed in Test Group-1 when administered with Antacid as compared to Controlled Group-1. Mean Cmax values showed a significant (p value 0.035) decrease from 44.14±2.3 to 33.1±0.8 µg/mL. Tmax, Area under curve, t1/2, Cl, Vd and Ke were not affected significantly. AUC increased from 195.7±8.9 µg.hr/mL to 222.8±14.7 µg.hr/mL. In contrast, test Group-2 showed an increase in dexibuprofen absorption. t1/2 increased significantly from 4.505±0.19 hrs to 6.216±0.36 hrs whereas Ke reduced from 0.159±0.00 to 0.116±0.006 hrs-1. Cmax increased from 44.877±2.263 to 51.721±0.096 µg/mL. CONCLUSION: It is concluded that concomitant intake of Al/Mg hydroxide antacid or food with dexibuprofen has an impact to significantly alter its pharmacokinetic parameters.