ABSTRACT
In-situ forming implants receive great attention for repairing serious bone injuries. The aim of the present study was to prepare novel chitosan in-situ forming implants (CIFI) loaded with bioactive glass nanoparticles and/or raloxifene hydrochloride (RLX). Incorporating raloxifene hydrochloride (RLX) as a selective estrogen receptor modulator was essential to make use of its anti-resorptive properties. The prepared formulae were tested for their in-vitro gelation time, drug release, injectability, rheological properties, erosion rate and morphological properties. Results revealed that the formulation composed of 1% (w/v) chitosan with 2% (w/v) NaHCO3 and 1% (w/v) bioactive glass nanoparticles (CIFI-BG) possessed the most sustained drug release profile which extended over four months with low burst release effect compared to the same formulation lacking bioactive glass nanoparticles (CIFI). Selected formulations were tested for their ability to enhance bone regeneration in induced puncture in rate tibia. Results declared that these formulations were able to enhance bone regeneration after 12 weeks in comparison to the untreated tibial punctures and that containing bioactive glass could be considered as novel approach for treatment of serious bone injuries which require long term treatment and internal mechanical bone support during healing.
Subject(s)
Bone Density Conservation Agents/chemical synthesis , Chitosan/chemical synthesis , Drug Compounding/methods , Nanoparticles/chemistry , Raloxifene Hydrochloride/chemical synthesis , Tibia/drug effects , Animals , Bone Density Conservation Agents/administration & dosage , Bone Density Conservation Agents/metabolism , Bone Regeneration/drug effects , Bone Regeneration/physiology , Chitosan/administration & dosage , Chitosan/metabolism , Disease Models, Animal , Drug Carriers/administration & dosage , Drug Carriers/chemistry , Drug Carriers/metabolism , Drug Evaluation, Preclinical/methods , Drug Implants/administration & dosage , Drug Implants/chemical synthesis , Drug Implants/metabolism , Glass/chemistry , Male , Nanoparticles/administration & dosage , Nanoparticles/metabolism , Raloxifene Hydrochloride/administration & dosage , Raloxifene Hydrochloride/metabolism , Rats , Rats, Sprague-Dawley , Tibia/injuries , Tibia/metabolism , Treatment OutcomeABSTRACT
Bone injury is very serious in elder people or osteoporotic patients. In-situ forming implants (IFI) for bone rebuilding are usually poly-lactic-co-glycolic acid (PLGA)-based, which have a burst release effect. This study aimed to prepare novel liquid lipid-based PLGA-IFI loaded with raloxifene hydrochloride for prolonged non-surgical treatment of bone injuries by applying solvent-induced phase inversion technique. Labrasol® and Maisine® were added to the selected IFI forming long lasting lipid-based IFI (LLL-IFI). The formulations were characterized by analysing their in-vitro drug release, solidification time, injectability, rheological properties, and DSC in addition to their morphological properties. Results revealed that the LLL-IFI composed of 10%w/v PLGA with a lactide to glycolide ratio of 75:25 with ester terminal and 10% Maisine® possessed the most sustained drug release and lowest burst effect, as well as delayed pore formation compared to its counterpart lacking Maisine®. The selected LLL-IFI and PLGA-IFI formulations were tested for their capability to enhance bone regeneration in bone injuries induced in rats. Both formulations succeeded in healing the bones completely with the superiority of LLL-IFI in the formation of well-organized bone structures lacking fibrous tissues. The results suggest that LLL-IFI and PLGA-IFI are innovative approaches for treating critical and non-critical sized bone injuries.
Subject(s)
Bone Density Conservation Agents/administration & dosage , Drug Carriers/chemistry , Drug Implants/administration & dosage , Osteoporotic Fractures/drug therapy , Raloxifene Hydrochloride/administration & dosage , Animals , Bone Density Conservation Agents/pharmacokinetics , Bone and Bones/drug effects , Bone and Bones/injuries , Chemistry, Pharmaceutical , Delayed-Action Preparations/administration & dosage , Delayed-Action Preparations/pharmacokinetics , Disease Models, Animal , Drug Evaluation, Preclinical , Drug Implants/pharmacokinetics , Drug Liberation , Humans , Injections, Intralesional , Male , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry , Porosity , Raloxifene Hydrochloride/pharmacokinetics , Rats , Surface PropertiesABSTRACT
CONTEXT: Topical treatment of skin disease needs to be strategic to ensure high drug concentration in the skin with minimum systemic absorption. OBJECTIVE: The aim of this study was to produce semisolid nanostructured lipid carrier (NLC) formulations, for topical delivery of the corticosteroid drug, diflucortolone valerate (DFV), with minimum systemic absorption. METHOD: NLC formulations were developed using a high shear homogenization combined with sonication, using Precirol® ATO5 or Tristearin® as the solid lipid, Capryol™ or isopropyl myristate as the liquid lipid and Poloxamer® 407 as surfactant. The present study addresses the influence of different formulations composition as solid lipid, liquid lipid types and concentrations on the physicochemical properties and drug release profile from NLCs. RESULTS AND DISCUSSION: DFV-loaded NLC formulations possessed average particle size ranging from 160.40 nm to 743.7 nm with narrow polydispersity index. The encapsulation efficiency was improved by adding the lipid-based surfactants (Labrasol® and Labrafil® M1944CS) to reach 68%. The drug release from the investigated NLC formulations showed a prolonged release up to 12 h. The dermatopharmacokinetic study revealed an improvement in drug deposition in the skin with the optimized DFV-loaded NLC formulation, in contrast to a commercial formulation. CONCLUSION: NLC provides a promising nanocarrier system that work as reservoir for targeting topical delivery of DFV.
