Liposomes are used for systemic delivery of chemotherapeutic drugs to reduce their nonspecific side effects. Liposomes can encapsulate hydrophilic and lipophilic drugs in the water compartment and the lipid membrane, respectively. However, typical drug loading capacity of liposomes by passive loading method is less than 1%. The low drug loading efficiency is problematic because it necessitates the use of a large amount of carrier materials that may cause undesirable biological effects. To increase drug loading in liposomes, weusedsupersaturated drug solutionswith gemcitabine (GEM) and doxorubicin (Dox) as examples. The prepared liposomes showed higher drug loading compared with passive loading, maintainedstabilityand provided sustained drug release for 48 hrs.

Liposomes are used for systemic delivery of chemotherapeutic drugs to reduce their nonspecific side effects. Liposomes can encapsulate hydrophilic and lipophilic drugs in the water compartment and the lipid membrane, respectively. However, typical drug loading capacity of liposomes by passive loading method is less than 1%. The low drug loading efficiency is problematic because it necessitates the use of a large amount of carrier materials that may cause undesirable biological effects. To increase drug loading in liposomes, weusedsupersaturated drug solutionswith gemcitabine (GEM) and doxorubicin (Dox) as examples. The prepared liposomes showed higher drug loading compared with passive loading, maintainedstabilityand provided sustained drug release for 48 hrs.

Liposomes are used for systemic delivery of chemotherapeutic drugs to reduce their nonspecific side effects. Liposomes can encapsulate hydrophilic and lipophilic drugs in the water compartment and the lipid membrane, respectively. However, typical drug loading capacity of liposomes by passive loading method is less than 1%. The low drug loading efficiency is problematic because it necessitates the use of a large amount of carrier materials that may cause undesirable biological effects. To increase drug loading in liposomes, weusedsupersaturated drug solutionswith gemcitabine (GEM) and doxorubicin (Dox) as examples. The prepared liposomes showed higher drug loading compared with passive loading, maintainedstabilityand provided sustained drug release for 48 hrs.

Liposomes are used for systemic delivery of chemotherapeutic drugs to reduce their nonspecific side effects. Liposomes can encapsulate hydrophilic and lipophilic drugs in the water compartment and the lipid membrane, respectively. However, typical drug loading capacity of liposomes by passive loading method is less than 1%. The low drug loading efficiency is problematic because it necessitates the use of a large amount of carrier materials that may cause undesirable biological effects. To increase drug loading in liposomes, weusedsupersaturated drug solutionswith gemcitabine (GEM) and doxorubicin (Dox) as examples. The prepared liposomes showed higher drug loading compared with passive loading, maintainedstabilityand provided sustained drug release for 48 hrs.

Liposomes are widely used for systemic delivery of chemotherapeutic agents to reduce their nonspecific side effects. Gemcitabine (Gem) makes a great candidate for liposomal encapsulation due to the short half-life and non-specific side effects; however, it has been difficult to achieve liposomal Gem with high drug loading capacity. Remote loading, which uses a transmembrane pH gradient to induce influx of drug and locks the drug in the core as a sulfate complex, does not serve Gem as efficiently as doxorubicin (Dox) due to the low pKa value of Gem. Existing studies have attempted to improve Gem loading capacity in liposomes by employing lipophilic Gem derivatives or creating a high concentration gradient for active loading into the hydrophilic cores (small volume loading). In this study we combine remote loading approach and small volume loading or hypertonic loading, a new approach to induce the influx of Gem into the preformed liposomes by high osmotic pressure, to achieve a Gem loading capacity of 9.4 – 10.3 wt% in contrast to 0.14 – 3.8 wt% of the conventional methods. Liposomal Gem showed a good stability during storage, sustained-release over 120 h in vitro, enhanced cellular uptake and improved cytotoxicity as compared to free Gem. Liposomal Gem showed a synergistic effect with liposomal Dox on Huh7 hepatocellular carcinoma cells. A mixture of liposomal Gem and liposomal Dox delivered both drugs to the tumor more efficiently than a free drug mixture and showed a relatively good anti-tumor effect in a xenograft model of hepatocellular carcinoma. This study shows that bioactive liposomal Gem with high drug loading capacity can be produced by remote loading combined with additional approaches to increase drug influx into the liposomes.

Liposomes are widely used for systemic delivery of chemotherapeutic agents to reduce their nonspecific side effects. Gemcitabine (Gem) makes a great candidate for liposomal encapsulation due to the short half-life and non-specific side effects; however, it has been difficult to achieve liposomal Gem with high drug loading capacity. Remote loading, which uses a transmembrane pH gradient to induce influx of drug and locks the drug in the core as a sulfate complex, does not serve Gem as efficiently as doxorubicin (Dox) due to the low pKa value of Gem. Existing studies have attempted to improve Gem loading capacity in liposomes by employing lipophilic Gem derivatives or creating a high concentration gradient for active loading into the hydrophilic cores (small volume loading). In this study we combine remote loading approach and small volume loading or hypertonic loading, a new approach to induce the influx of Gem into the preformed liposomes by high osmotic pressure, to achieve a Gem loading capacity of 9.4 – 10.3 wt% in contrast to 0.14 – 3.8 wt% of the conventional methods. Liposomal Gem showed a good stability during storage, sustained-release over 120 h in vitro, enhanced cellular uptake and improved cytotoxicity as compared to free Gem. Liposomal Gem showed a synergistic effect with liposomal Dox on Huh7 hepatocellular carcinoma cells. A mixture of liposomal Gem and liposomal Dox delivered both drugs to the tumor more efficiently than a free drug mixture and showed a relatively good anti-tumor effect in a xenograft model of hepatocellular carcinoma. This study shows that bioactive liposomal Gem with high drug loading capacity can be produced by remote loading combined with additional approaches to increase drug influx into the liposomes.

Liposomes are widely used for systemic delivery of chemotherapeutic agents to reduce their nonspecific side effects. Gemcitabine (Gem) makes a great candidate for liposomal encapsulation due to the short half-life and non-specific side effects; however, it has been difficult to achieve liposomal Gem with high drug loading capacity. Remote loading, which uses a transmembrane pH gradient to induce influx of drug and locks the drug in the core as a sulfate complex, does not serve Gem as efficiently as doxorubicin (Dox) due to the low pKa value of Gem. Existing studies have attempted to improve Gem loading capacity in liposomes by employing lipophilic Gem derivatives or creating a high concentration gradient for active loading into the hydrophilic cores (small volume loading). In this study we combine remote loading approach and small volume loading or hypertonic loading, a new approach to induce the influx of Gem into the preformed liposomes by high osmotic pressure, to achieve a Gem loading capacity of 9.4 – 10.3 wt% in contrast to 0.14 – 3.8 wt% of the conventional methods. Liposomal Gem showed a good stability during storage, sustained-release over 120 h in vitro, enhanced cellular uptake and improved cytotoxicity as compared to free Gem. Liposomal Gem showed a synergistic effect with liposomal Dox on Huh7 hepatocellular carcinoma cells. A mixture of liposomal Gem and liposomal Dox delivered both drugs to the tumor more efficiently than a free drug mixture and showed a relatively good anti-tumor effect in a xenograft model of hepatocellular carcinoma. This study shows that bioactive liposomal Gem with high drug loading capacity can be produced by remote loading combined with additional approaches to increase drug influx into the liposomes.

Liposomes are widely used for systemic delivery of chemotherapeutic agents to reduce their nonspecific side effects. Gemcitabine (Gem) makes a great candidate for liposomal encapsulation due to the short half-life and non-specific side effects; however, it has been difficult to achieve liposomal Gem with high drug loading capacity. Remote loading, which uses a transmembrane pH gradient to induce influx of drug and locks the drug in the core as a sulfate complex, does not serve Gem as efficiently as doxorubicin (Dox) due to the low pKa value of Gem. Existing studies have attempted to improve Gem loading capacity in liposomes by employing lipophilic Gem derivatives or creating a high concentration gradient for active loading into the hydrophilic cores (small volume loading). In this study we combine remote loading approach and small volume loading or hypertonic loading, a new approach to induce the influx of Gem into the preformed liposomes by high osmotic pressure, to achieve a Gem loading capacity of 9.4 – 10.3 wt% in contrast to 0.14 – 3.8 wt% of the conventional methods. Liposomal Gem showed a good stability during storage, sustained-release over 120 h in vitro, enhanced cellular uptake and improved cytotoxicity as compared to free Gem. Liposomal Gem showed a synergistic effect with liposomal Dox on Huh7 hepatocellular carcinoma cells. A mixture of liposomal Gem and liposomal Dox delivered both drugs to the tumor more efficiently than a free drug mixture and showed a relatively good anti-tumor effect in a xenograft model of hepatocellular carcinoma. This study shows that bioactive liposomal Gem with high drug loading capacity can be produced by remote loading combined with additional approaches to increase drug influx into the liposomes.

Verapamil hydrochloride (Vp-HCl) is a calcium channel blocker and class IV antiarrythmic drug. Its oral bioavailability is about 20- 30% because of the extensive first-pass metabolism, so it is advisable to prepare the drug in a buccoadhesive dosage forms to bypass first-pass metabolism and thus achieving constant plasma concentrations during treatment of chronic hypertension. Certain bioadhesive polymers were used either singly or in combinations at different ratios in order to select the best matrix forming tablets with satisfactory drug release, characteristic bioadhesiveness and swelling properties. It was found that the drug release decreased by increasing the concentration of the polymer in all the studied formulations and the drug release from using polymer blends is slower than those containing single polymer. Tablet formula containing either 30% (w/w) hydroxypropyl methyl cellulose 15000(HPMC 15000) & 10% (w/w) sodium carboxymethyl cellulose (SCMC), or containing 5% (w/w) carbopol 934P (Cp934P) with either 15% (w/w) HPMC 15000 or 30% (w/w) sodium alginate (NaAlg) was developed to a satisfactory level in terms of drug release, bioadhesive performance and swelling properties. Plasma concentration time curves obtained following buccal administration of the optimal prepared buccoadhesive tablets to rabbits showed evidence of sustained release of Vp-HCl. Bioavailability of Vp-HCl formulated tablets formulae (T31, T35 & T38) was approximately two times higher than that achieved after oral administration of commercial tablets.

Verapamil hydrochloride (Vp-HCl) is a calcium channel blocker and class IV antiarrythmic drug. Its oral bioavailability is about 20- 30% because of the extensive first-pass metabolism, so it is advisable to prepare the drug in a buccoadhesive dosage forms to bypass first-pass metabolism and thus achieving constant plasma concentrations during treatment of chronic hypertension. Certain bioadhesive polymers were used either singly or in combinations at different ratios in order to select the best matrix forming tablets with satisfactory drug release, characteristic bioadhesiveness and swelling properties. It was found that the drug release decreased by increasing the concentration of the polymer in all the studied formulations and the drug release from using polymer blends is slower than those containing single polymer. Tablet formula containing either 30% (w/w) hydroxypropyl methyl cellulose 15000(HPMC 15000) & 10% (w/w) sodium carboxymethyl cellulose (SCMC), or containing 5% (w/w) carbopol 934P (Cp934P) with either 15% (w/w) HPMC 15000 or 30% (w/w) sodium alginate (NaAlg) was developed to a satisfactory level in terms of drug release, bioadhesive performance and swelling properties. Plasma concentration time curves obtained following buccal administration of the optimal prepared buccoadhesive tablets to rabbits showed evidence of sustained release of Vp-HCl. Bioavailability of Vp-HCl formulated tablets formulae (T31, T35 & T38) was approximately two times higher than that achieved after oral administration of commercial tablets.