Enhanced wound healing potential of arabincoside B isolated from Caralluma Arabica in rat model; a possible dressing in veterinary practice.

BACKGROUND: Wound management is a critical procedure in veterinary practice. A wound is an injury that requires the body's cells' alignment to break down due to external assault, such as trauma, burns, accidents, and diseases. Re-epithelization, extracellular matrix deposition, especially collagen, inflammatory cell infiltration, and development of new blood capillaries are the four features that are used to evaluate the healing process. Using a natural extract for wound management is preferred to avoid the side effects of synthetic drugs. The current study aimed to assess the effect of major pregnane glycoside arabincoside B (AR-B) isolated from Caralluma arabica (C. arabica) for the wound healing process. METHOD: AR-B was loaded on a gel for wound application. Rats were randomly distributed into six groups: normal, positive control (PC), MEBO®, AR-B 0.5%, AR-B 1%, and AR-B 1.5%, to be 6 animals in each group. Wounds were initiated under anesthesia with a 1 cm diameter tissue needle, and treatments were applied daily for 14 days. The collected samples were tested for SOD, NO, and MDA. Gene expression of VEGF and Caspase-3. Histopathological evaluation was performed at two-time intervals (7 and 14 days), and immunohistochemistry was done to evaluate α -SMA, TGF-ß, and TNF-α. RESULT: It was found that AR-B treatment enhanced the wound healing process. AR-B treated groups showed reduced MDA and NO in tissue, and SOD activity was increased. Re-epithelization and extracellular matrix deposition were significantly improved, which was confirmed by the increase in TGF-ß and α -SMA as well as increased collagen deposition. TNF-α was reduced, which indicated the subsiding of inflammation. VEGF and Caspase-3 expression were reduced. CONCLUSION: Our findings confirmed the efficiency of AR-B in enhancing the process of wound healing and its potential use as a topical wound dressing in veterinary practice.

Sonophoresis-assisted transdermal delivery of antimigraine-loaded nanolipomers: Radio-tracking, histopathological assessment and in-vivo biodistribution study.

Migraine is a disabling neurovascular polygenic disorder affecting life quality with escorted socioeconomic encumbrances. Herein, we investigated the consolidated amalgamation of passive lipomer approach alongside active sonophoresis assisted transdermal delivery of zolmitriptan (ZT) using high frequency ultrasound pre-treatment protocol to mitigate migraine attacks. A modified nanoprecipitation technique was utilized to prepare zolmitriptan loaded lipomers (ZTL) adopting 23 factorial design. Three factors were scrutinized namely lipid type, ZT: lipid ratio and ZT: Gantrez® ratio. The prepared systems were characterized regarding particle size, zeta potential, polydispersity index, entrapment efficiency and in-vitro release studies. The best achieved ZTL system was evaluated for ZT- Gantrez® intermolecular interactions, drug crystallinity, morphology, ex-vivo permeation and histopathological examination. Finally, a comparative in-vivo biodistribution study through radiotracking technique using Technetium-99 m was adopted. L2 was the best-achieved ZTL system with respect to spherical particle size (390.7 nm), zeta-potential (-30.8 mV), PDI (0.2), entrapment efficiency (86.2%), controlled release profile, flux (147.13 µg/cm2/hr) and enhancement ratio (5.67). Histopathological studies proved the safety of L2 system upon application on skin. L2 revealed higher brain Cmax (12.21 %ID/g), prolonged brain MRT (8.67 hr), prolonged brain 0.23 hr), significantly high relative bioavailability (2929.36%) and similar brain Tmax (0.5 hr) compared to I.V. route with higher brain/blood ratio. Thus, sonophoresis assisted transdermal delivery of ZTL offers a propitious alterative to alleviate migraine symptoms.

Darifenacin Self-assembled Liquid Crystal Cubic Nanoparticles: a Sustained Release Approach for an Overnight Control of Overactive Bladder.

The current study is regarding the development and characterization of Darifenacin-loaded self-assembled liquid crystal cubic nanoparticles (LCCN). An anhydrous approach was used for the preparation of these cubic nanoparticles using a hydrotropic agent (propylene glycol), with minimal energy input. Upon dispersion in aqueous medium, the system was successfully transformed to cubosomal nanoparticles counterpart as depicted by transmission electron micrographs. A Box-Behnken design was used to optimize formulation variables, namely A: amount of GMO, B: amount of Pluronic F127, C: amount of PG, and D: amount of HPMC. The design has generated 29 formulae which were tested regarding drug content uniformity, dispersibility in water, particle size, zeta potential, polydispersity index, and in vitro release behavior. The numerical optimization algorithms have generated an optimized formula with high desirability ≈ 1. The optimized formula displayed small particle size, good homogeneity, and zeta potential along with controlled in vitro release profile and ex vivo permeation through rabbit intestine. Thus, self-assembled LCCN might offer an alternative anhydrous approach for the preparation of cubosomal nanoparticles with controlled release profile for a possibly better control of overactive bladder syndrome which tremendously affect the overall life quality.

Drotaverine Hydrochloride Superporous Hydrogel Hybrid System: a Gastroretentive Approach for Sustained Drug Delivery and Enhanced Viscoelasticity.

This study aims to prepare drotaverine hydrochloride superporous hydrogel hybrid systems (DSHH systems) to prolong its residence time in the stomach, provide extended release and reduce its frequency of administration. Drotaverine hydrochloride (DRH) is a spasmolytic drug that suffers from brief residence due to intestinal hypermotility during diarrheal episodes associated with gastrointestinal colics resulting in low bioavailability and repeated dosing. Eight DSHH systems were prepared using gas blowing technique. The prepared DSHH systems were evaluated regarding their morphology, incorporation efficiency, density, porosity, swelling ratio, viscoelastic property, erosion percentage and release kinetics. The FH8 formula containing equal proportion of chitosan (3%) /polyvinyl alcohol (3%) as strengthener and crosslinked with tripolyphosphate showed the highest incorporation efficiency (91.83 ± 1.33%), good swelling ratio (28.32 ± 3.15% after 24 h), optimum viscoelastic properties (60.19 ± 3.82 kPa) and sustained release profile (88.03 ± 2.15% after 24 h). A bioequivalence study was done to compare the bioavailability of the candidate formula versus Spasmocure®. Statistical analysis showed significant (P < 0.05) increase in bioavailability 2.7 folds with doubled Tmax (4 h) compared to the marketed product (2 h). These results declared that the superporous hydrogel hybrid systems could be a potential gastroretentive approach for the sustained delivery of drugs with short residence time with enhanced viscoelasticity.

Hyaluronic Acid Conjugated Metformin-Phospholipid Sonocomplex: A Biphasic Complexation Approach to Correct Hypoxic Tumour Microenvironment.

PURPOSE: Development of hyaluronic acid conjugated metformin-phospholipid sonocomplexes (HA-MPS), a biphasic complexation product compiled for enhancing both the lipophilicity and targeting potential of Metformin (MET) to CD44 receptors on pancreatic cancer. METHODS: MET was chemically conjugated to hyaluronic acid (HA) via amide coupling reaction. Then, the HA conjugated MET was physically conjugated to Lipoid™S100 via ultrasound irradiation. A combined D-optimal design was implemented to statistically optimize formulation variables. The HA-MPS were characterized through solubility studies, partition coefficient, drug content uniformity, particle size and zeta potential. The optimized HA-MPS was tested via proton nuclear magnetic resonance, infrared spectroscopy to elucidate the nature of physicochemical interactions in the complex which was further scrutinized on molecular level via molecular docking and dynamic simulation. RESULTS: The solubility and partition studies showed a lipophilicity enhancement up to 67 folds as they adopted inverted micelles configuration based on the packing parameter hypothesis. The optimized HA-MPS showed 11.5 folds lower IC50, extra 25% reduction in oxygen consumption rate, better reduction in hypoxia-inducible factor and reactive oxygen species in MiaPaCa-2 cells. CONCLUSION: These results proved better internalization of MET which was reflected by abolishing hypoxic tumour microenvironment, a mainstay toward a normoxic and less resistant pancreatic cancer.

Zaleplon loaded bi-layered chronopatch: A novel buccal chronodelivery approach to overcome circadian rhythm related sleep disorder.

The aim of this study was to develop a novel buccal bi-layered chronopatch capable of eliciting pulsatile release pattern of drugs treating diseases with circadian rhythm related manifestation. Zaleplon (ZLP) was used as a model drug intended to induce sleep and to treat middle of night insomnia. The chronopatch was prepared adopting double casting technique. The first layer was composed of a controlled release patch containing ZLP-Precirol melt granules intended to release ZLP in a sustained manner to maintain sleep and to prevent early morning awakening. The second layer was composed of a fast release lyophilized buccal disc containing ZLP loaded SNEDDS (Z-SNEDDS) intended for rapid sleep induction. Pharmacokinetic parameters of ZLP from the chronopatch were compared to those of the immediate release capsule, Siesta®, as reference in Mongrel dogs using a randomized crossover design. The appearance of two peaks having two Cmax and Tmax proved the pulsatile release pattern. The increase in relative bioavailability of ZLP from the chronopatch was 2.63 folds. The results revealed the ability of the developed ZLP loaded bi-layered chronopatch to be a candidate for overcoming early morning awakening without middle of night dose administration.