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Muhammad Ahmad Mahmood,1,2 Asadullah Madni,1 Mubashar Rehman,3 Muhammad Abdur Rahim,1 Abdul Jabar1 1Department of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur 63100, Pakistan; 2Drug Testing Laboratory, Bahawalpur 63100, Pakistan; 3Faculty of Pharmacy, University of Central Punjab, Lahore 54000, PakistanCorrespondence: Asadullah MadniDepartment of Pharmacy, The Islamia University of Bahawalpur, Khawaja Fareed Campus, Railway Road, Bahawalpur, Punjab, PakistanTel +92 62 925 5243Fax +92 62 925 5565Email asadpharmacist@hotmail.comIntroduction: Polymeric nanoparticles are potential carriers for the efficient delivery of hydrophilic and hydrophobic drugs due to their multifaceted applications. Docetaxel is relatively less hydrophobic and twice as potent as paclitaxel. Like other taxane chemotherapeutic agents, docetaxel is not well tolerated and shows toxicity in the patients. Nanoencapsulation of potent chemotherapeutic agents has been shown to improve tolerability and therapeutic outcome. Therefore, the present study was designed to fabricate chitosan and sodium tripolyphosphate (STPP) based on ionically cross-linked nanoparticles for sustained release of docetaxel.Methods: Nanoparticles were prepared by the ionic-gelation method by dropwise addition of the STPP solution into the chitosan solution in different ratios. CNPs were characterized for post-formulation parameters like size, zeta potential, scanning electron microscope (SEM), FTIR, DSC/TGA, pXRD, and in-vitro drug release, as well as for acute oral toxicity studies in Wistar rats.Results and discussion: The optimized docetaxel loaded polymeric nanoparticles were in the size range (172.6nm–479.65 nm), and zeta potential (30.45–35.95 mV) required to achieve enhanced permeation and retention effect. In addition, scanning electron microscopy revealed rough and porous surface, whereas, FTIR revealed the compatible polymeric nanoparticles. Likewise, the thermal stability was ensured through DSC and TG analysis, and powder X-ray diffraction analysis exhibited solid-state stability of the docetaxel loaded nanoparticles. The in-vitro drug release evaluation in phosphate buffer saline (pH 7.4) showed sustained release pattern, i.e. 51.57–69.93% within 24 hrs. The data were fitted to different release kinetic models which showed Fickian diffusion as a predominant release mechanism (R2= 0.9734–0.9786, n= 0.264–0.340). Acceptable tolerability was exhibited by acute oral toxicity in rabbits and no abnormality was noted in growth, behavior, blood biochemistry or histology and function of vital organs.Conclusion: Ionically cross-linked chitosan nanoparticles are non-toxic and biocompatible drug delivery systems for sustained release of chemotherapeutic agents, such as docetaxel.Keywords: tripolyphosphate, ionic gelation, sustained release, targeting, biocompatible, biodegradable

Proniosomes (PN) are the dry water-soluble carrier systems that may enhance the oral bioavailability, stability, and topical permeability of therapeutic agents. The low solubility and low oral bioavailability due to extensive first pass metabolism make Pentazocine as an ideal candidate for oral and topical sustained release delivery. The present study was aimed to formulate the PNs by quick slurry method that are converted to niosomes (liquid dispersion) by hydration, and subsequently formulated to semisolid niosomal gel. The PNs were found in spherical shape in the SEM and stable in the physicochemical and thermal analysis (FTIR, TGA, and XRD). The quick slurry method produced high recovery (> 80% yield) and better flow properties (θ = 28.1–37.4°). After hydration, the niosomes exhibited desirable entrapment efficiency (44.45–76.23%), size (4.98–21.3 μm), and zeta potential (− 9.81 to − 21.53 mV). The in vitro drug release (T100%) was extended to more than three half-lives (2–4 h) and showed good fit to Fickian diffusion indicated by Korsmeyer-Peppas model (n = 0.136–0.365 and R2 = 0.9747–0.9954). The permeation of niosomal gel was significantly enhanced across rabbit skin compared to the pure drug-derived gel. Therefore, the PNs are found promising candidates for oral as dissolution enhancement and sustained release for oral and topical delivery of pentazocine for the management of cancer pain.

Proliposomes (PLs) are smart provesicular drug delivery system regarding improvement in solubility, oral bioavailability, stability, and permeability of the therapeutic agents. In this study, glibenclamide (GLB) loaded PLs and liposomes for oral delivery, and liposomal gel for transdermal delivery of GLB has been developed. A slurry method was employed to fabricate PLs, followed by hydration and incorporation of gelling agent for liposomes and liposomal gel, respectively. The developed proliposomes (PLs) were dry, free-flowing (θ; 29.0°–37.1°) with optimum percentage yield (81–92%), entrapment efficiency (67.68–83.11%), compatibility, solid-state stability, and thermal stability. In addition, the liposomal formulations produced suitable vesicle size (510 nm–1436 nm), optimum colloidal stability and monodispersity, such that the optimized formulation (FGP-4) presented vesicle size of 510 ± 4 nm, zeta potential −11.5 ± 2.0 mV and PDI of 0.41 ± 0.06. The in vitro drug dissolution data showed the enhanced GLB release (>90% in 12 h) from the system. Moreover, the permeation studies revealed 2.27 folds enhanced permeability of liposomal gel (FGP-4 gel) compared to drug-loaded gel. An acute oral toxicity study utilizing Wistar rats revealed the safety of PLs. The developed PLs provided enhanced in vitro drug dissolution and liposomal gel provided improved ex vivo permeation. The GLB loaded PLs and liposomal gel may better control Diabetes Mellitus through oral and topical routes.

The current study aimed to develop novel pH independent microparticles loaded with ropinirole (ROP) for sustained drug release. Eudragit RS 100 was used as release retardant and microparticles were fabricated by oil-in-oil emulsion solvent evaporation method. A three-factor three-level Box-Behnken design using Design-Expert software was employed to optimize formulation variables. Ropinirole loaded microparticles were evaluated with respect to morphology, particle size, encapsulation efficiency, and in vitro release profile. Optical microscopy and SEM micrographs indicated spherical shape with smooth surface and well-defined boundary. The particle size was in the range of 98.86 to 236.29 μm, being significantly increased with increasing polymer concentration. Higher polymer load also increased the thickness of internal polymer network, which led to reduced drug loss and higher entrapment efficiency (89%). The cumulative in vitro release was found to be in the range of 54.96 to 99.36% during the release studies (12 h) following zero order release kinetics and non-Fickian diffusion pattern. The developed microparticles have the potential to sustain the release of ropinirole, which may lead to a reduction in its adverse effects and improved management of Parkinson’s disease.

Mubashar Rehman,1 Asadullah Madni,1 Ayesha Ihsan,2 Waheed Samraiz Khan,2 Muhammad Imran Khan,1 Muhammad Ahmad Mahmood,1 Muhammad Ashfaq,1 Sadia Zafar Bajwa,2 Imran Shakir31Department of Pharmacy, Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Pakistan; 2Nanobiotechnology Group, Industrial Biotechnology Division, National Institute of Biotechnology and Genetic Engineering, Faisalabad, Pakistan; 3Sustainable Energy Technologies (SET) centre, College of Engineering, King Saud University, Riyadh, Saudi ArabiaAbstract: Binary fatty acid mixture-based solid lipid nanoparticles (SLNs) were prepared for delivery of diacerein, a novel disease-modifying osteoarthritis drug, with and without simultaneously loaded gold nanoparticles (GNPs). In order to optimize SLNs for temperature-responsive release, lipid mixtures were prepared using different ratios of solid (stearic acid or lauric acid) and liquid (oleic acid) fatty acids. SLNs were prepared by microemulsification (53 nm), hot melt encapsulation (10.4 nm), and a solvent emulsification-evaporation technique (7.8 nm). The physicochemical characteristics of SLNs were studied by Zetasizer, Fourier transform infrared, and X-ray diffraction analysis. High encapsulation of diacerein was achieved with diacerein-loaded and simultaneously GNP-diacerein-loaded SLNs. In vitro dissolution studies revealed a sustained release pattern for diacerein over 72 hours for diacerein-loaded SLNs and 12 hours for GNP-diacerein-loaded SLNs. An increase in diacerein payload increased the release time of diacerein while GNPs decreased it. In addition, rapid release of diacerein over 4 hours was observed at 40°C (melting point of optimized fatty acid mixture), demonstrating that these binary SLNs could be used for thermoresponsive drug delivery. Kinetic modeling indicated that drug release followed zero order and Higuchi diffusion models (R2>0.9), while the Korsmeyer-Peppas model predicted a diffusion release mechanism (n