Injectable systems of chitosan in situ forming composite gel incorporating linezolid-loaded biodegradable nanoparticles for long-term treatment of bone infections.

The objective of the current study was to create an efficient, minimally invasive combined system comprising in situ forming hydrogel loaded with both spray-dried polymeric nanoparticles encapsulating linezolid and nanohydroxyapatite for local injection to bones or their close vicinity. The developed system was designed for a dual function namely releasing the drug in a sustained manner for long-term treatment of bone infections and supporting bone proliferation and new tissues generation. To achieve these objectives, two release sustainment systems for linezolid were optimized namely a composite in situ forming chitosan hydrogel and spray-dried PLGA/PLA solid nanoparticles. The composite, in situ forming hydrogel of chitosan was prepared using two different gelling agents namely glycerophosphate (GP) and sodium bicarbonate (NaHCO3) at 3 different concentrations each. The spray-dried linezolid-loaded PLGA/PLA nanoparticles were developed using a water-soluble carrier (PVP K30) and a lipid soluble one (cetyl alcohol) along with 3 types of DL-lactide and/or DL-lactide-co-glycolide copolymer using nano-spray-drying technique. Finally, the optimized spray-dried linezolid nanoparticles were incorporated into the optimized composite hydrogel containing nanohydroxy apatite (nHA). The combined hydrogel/nanoparticle systems displayed reasonable injectability with excellent gelation time at 37 °C. The optimum formulae sustained the release of linezolid for 7-10 days, which reveals its ability to reduce the frequency of injection during the course of treatment of bones infections and increase the patients' compliance. They succeeded to alleviate the bone infections and the associated clinical, biochemical, radiological, and histopathological changes within 2-4 weeks of injection. As to the state of art in this study and to the best of our knowledge, no such complete and systematic study on this type of combined in situ forming hydrogel loaded with spray-dried nanoparticles of linezolid is available yet in literatures.

Novel anti-psoriatic nanostructured lipid carriers for the cutaneous delivery of luteolin: A comprehensive in-vitro and in-vivo evaluation.

Psoriasis is a prevalent laborious inflammation in skin with alternate phases of remission and relapses. The current study sought to develop nanostructured lipid carriers (NLCs) having enhanced skin deposition as well as augmented anti-inflammatory potential, to repurpose the use of luteolin (Lut), a flavonoid, in the treatment of psoriasis. NLCs were prepared using different oils having reported anti-inflammatory activity and evaluated in terms of size, surface charge, entrapment efficiency, stability upon storage, in-vitro anti-inflammatory potential, surface morphology, in-vitro release profile and release kinetics, and ex-vivo skin deposition. In-vivo animal studies were conducted on the optimized formula using imiquimod-induced psoriasis rat model. The prepared NLCs were nanosized ranging from 202 to 538 nm, negatively charged with values having the range of -13.10 to -19.26 mV with high entrapment efficiency values ranging from 84.21 to 96.53% and high in-vitro anti-inflammatory potential compared to the blank and control formulations. Furthermore, NLCs demonstrated adequate storage stability demonstrated by slightly significant change in their colloidal properties. The prepared nanoparticles exhibited sustained drug release up to 24 h and succeeded in enhancing the skin deposition of Lut by 3.4-fold higher in stratum corneum, epidermis and dermis compared to Lut suspension with minimum transdermal delivery. In-vivo assessment of psoriasis was carried out morphologically, histopathologically and biochemically and results revealed significant augmentation of the anti-psoriatic efficacy of Lut upon its encapsulation in NLCs compared to free Lut suspension. The developed system proved to be an influential drug delivery system providing potent anti-psoriatic therapy, paving the way for futuristic clinical investigations.

Optimization of transdermal atorvastatin calcium - Loaded proniosomes: Restoring lipid profile and alleviating hepatotoxicity in poloxamer 407-induced hyperlipidemia.

In an attempt to optimize the anti- hyperlipidemic effect and reduce statins induced hepatotoxicity, Atorvastatin Calcium (ATC) transdermal proniosomal gel (PNG) was developed. Different non-ionic surfactants (NISs) (Spans, Tweens, Cremophor RH 40 and Brij 52) were incorporated in the vesicle's lipid bilayer, in combination with lecithin. PNG formulae were characterized for encapsulation efficiency percent (% EE), vesicle size, polydispersity index (PDI) and zeta potential (ZP). Ex-vivo permeation study was performed using full thickness rat skin measuring drug flux and skin permeability coefficients. The pharmacodynamic performance of optimized transdermal ATC- PNG on both lipid profile and liver biomarkers was assessed and compared to oral ATC administration in poloxamer 407-induced hyperlipidemic rats. The liver tissues were subjected to histological examination as well. The results revealed nano-size range vesicles with relatively high ATC entrapment efficiency. Ex-vivo results demonstrated the permeation superiority of ATC proniosomes over free drug. Pharmacodynamic study revealed that transdermal administration of ATC- PNG succeeded in retaining the anti-hyperlipidemic efficacy of orally administered ATC without elevating liver biomarkers. The histological examination signified the role of optimized ATC-PNG in hindering statin- induced hepatocellular damage. The obtained results suggested a promising, easy-to-manufacture and effective ATC proniosomal gel for safe treatment of hyperlipidemia.

Colloidal (-)-epigallocatechin-3-gallate vesicular systems for prevention and treatment of skin cancer: A comprehensive experimental study with preclinical investigation.

Skin carcinogenesis is a common malignancy affecting humans worldwide, which could benefit from nutraceuticals as a solution to the drawbacks of conventional skin cancer treatment. (-)-epigallocatechin-3-gallate (EGCG) is a promising nutraceutical in this regard; however, it suffers chemical instability and low bioavailability resulting in inefficient delivery. Therefore, EGCG encapsulation in ultradeformable colloidal vesicular systems, namely: penetration enhancer-containing vesicles (PEVs), ethosomes and transethosomes (TEs) for topical administration has been attempted in this study to overcome the problems associated with the use of free EGCG. The prepared vesicles were characterized for their entrapment efficiency, TEM visualization, chemical compatibility, antioxidant properties, ex-vivo skin deposition, photodegradation and physical stability after storage. Most of the prepared vesicles exhibited reasonable skin deposition and preservation of the inherent antioxidant properties of EGCG with good physical stability. EGCG-loaded PEVs and TEs exhibited an inhibitory effect on epidermoid carcinoma cell line (A431) in addition to reduced tumor sizes in mice, confirmed with histopathological analysis and biochemical quantification of skin oxidative stress biomarkers; glutathione, superoxide dismutase and catalase, as well as lipid peroxidation. EGCG PEVs succeeded in offering an effective delivery system targeting skin cancer, which is worthy of further experimentation.