Enhancement of bioavailability through transdermal drug delivery of paliperidone palmitate-loaded nanostructured lipid carriers.

Aim: The work describes enhanced bioavailability of paliperidone palmitate through transdermal delivery using nanostructured lipid carriers (NLC). Materials & methods: NLCs were formulated by nanoprecipitation method followed by incorporation in transdermal patch and physicochemical characterization. Results: NLCs showed high percentage entrapment efficiency of 83.44 ± 0.8%, drug loading of 24.75 ± 1.10% (w/w), particle size of 173.8 ± 3.25 nm, polydispersity index of 0.143 ± 0.05 and zeta potential of -15.9 ± 0.75 mV. In vitro and ex vivo studies indicated zero-order controlled drug release from NLCs and transdermal patch up to 48 h. Pharmacokinetic studies indicated 1.76-fold enhanced bioavailability by transdermal route as compared with oral drug delivery. Conclusion: From the results, it was concluded that drug-loaded NLCs-transdermal patch is promising drug delivery system for poorly bioavailable drugs.

Design and evaluation of hyaluronic acid-coated PLGA nanoparticles of raloxifene hydrochloride for treatment of breast cancer.

CONTEXT: In the present study, hyaluronic acid (HA)-coated raloxifene-loaded poly(l-lactic-co-glycolic acid) (PLGA) nanoparticles have been developed to improve the anticancer potential and reduce side effects associated with the drug. AIM AND OBJECTIVES: The investigation was aimed to formulate and optimize raloxifene hydrochloride (RALH)-loaded PLGA nanoparticles with surface modification using HA as a targeting moiety. To perform physicochemical characterization, in vitro cytotoxicity study (using MCF-7), in vitro drug release study and in vivo pharmacodynamic study of optimized formulation. METHODOLOGY: Raloxifene hydrochloride-loaded PLGA nanoparticles were prepared by nanoprecipitation technique, followed by surface modification with HA. Formulation was optimized by using 23 factorial design and characterized by physicochemical, in vitro drug release, in vitro cytotoxicity studies, and in vivo pharmacokinetics. RESULTS AND DISCUSSION: The particle size, PDI, zeta potential, entrapment efficiency, and loading capacity of spherically shaped RALH-loaded nanoparticles were 207.3 ± 4.2 d.nm, 0.218 ± 0.127, -.127 mV, 43.75 ± 1.2%, and 7.55 ± 1.14%, respectively. The in vitro drug release showed sustained release and followed Korsmeyer-Peppas model with non-Fickian release pattern. The in vitro cytotoxicity study of drug-loaded NPs by MTT assay on MCF-7 breast carcinoma cell showed anti-cancer activity after 48 h of treatment. CONCLUSION: The results of the present investigation suggested that RALH-loaded HA-modified PLGA nanoparticles showed sustained drug release with anticancer activity and can be a promising approach for treatment of breast cancer.

Formulation of polymeric nanoparticles of antidepressant drug for intranasal delivery.

Aim: The manuscript describes the performance of nanoparticles loaded with antidepressant drug for nose-to-brain drug delivery. Materials & methods: Poly-lactic-co-glycolic acid-loaded nanoparticles of agomelatine were prepared by nanoprecipitation method using poloxamer 407 as stabilizer. The process parameters were optimized using factorial design. Results: The drug-loaded nanoparticles having low particle size (<200 nm) with narrow size distribution and required zeta potential (-22.7 mV) to avoid aggregation showed sustained release profile and were found to have higher permeability as observed from ex vivo studies when compared with plain drug suspension. Histopathology test showed that the optimized formulation was free from nasal toxicity on the goat nasal mucosa. Pharmacodynamic study showed significant reduction in immobility time in rats treated with the formulation which indicated antidepressant activity of the formulation. Conclusion: The prepared agomelatin-loaded poly-lactic-co-glycolic acid nanoparticles showed prominent antidepressant activity by nose-to-brain delivery as observed from various studies.

Solid lipid nanoparticles as an efficient drug delivery system of olmesartan medoxomil for the treatment of hypertension.

The aim of the current investigation was to develop solid lipid nanoparticles of olmesartan medoxomil using hot homogenization method to improve its oral bioavailability. Central composite design was applied to optimize the formulation variables; lipid X1 (Glyceryl monostearate) and surfactant X2 (Poloxamer: Tween 80). The particle sizes were in the nanometer range and spherical shaped for all prepared solid lipid nanoparticles formulations and the zeta potential absolute values were high, predicting good long-term stability. In vitro study of olmesartan loaded solid lipid nanoparticle exhibited controlled release profile for at least 24 h. The rate and extent of drug diffusion was studied using dialysis sac, rat's stomach and intestine tissues; study demonstrated that drug release from the solid lipid nanoparticles was significantly higher than drug suspension. In vivo pharmacokinetic study of olmesartan loaded solid lipid nanoparticles revealed higher Cmax of 1610 ng/mL, higher AUC of 15492.50 ng/mL and increased relative bioavailability by almost 2.3 folds compared to marketed formulation. These results clearly indicate that olmesartan loaded solid lipid nanoparticles are shown to have enhanced bioavailability and effective therapeutic result and thus would be an excellent way to treat hypertension. Hence, these solid lipid nanoparticles could represent as a great potential for a possible alternative to conventional oral formulation in the treatment of hypertension.

Formulation and statistical optimization of intravenous temozolomide-loaded PEGylated liposomes to treat glioblastoma multiforme by three-level factorial design.

The aim of the presented study was to develop PEGylated liposomes of Temozolomide (TMZ) that provide optimum drug concentration at tumor site. Reverse phase evaporation (REV) method was used to prepare TMZ-loaded PEGylated liposomes. Formulation was optimized by using design expert software by 32 factorial design. The physicochemical properties including size, morphology, entrapment efficiency, drug loading, etc. of formulated liposomes were evaluated. Finally, the optimized formulation was selected for in vitro drug release and stability study. In vivo pharmacokinetic study in rats showed that TMZ-loaded PEGylated liposomes leads to 1.6-fold increase in AUCTotal in blood and 4.2-fold increase in brain as compared to free drug solution. This formulated PEGylated liposomes offers a promising approach for treatment of Glioblastoma Multiforme.