A study on liposomal encapsulation of a lipophilic prodrug of LHRH

Abstract

This study aimed at evaluating whether derivatization of luteinizing hormone-releasing hormone (LHRH) peptide with an amphiphilic lipoamino acid moiety could allow, along with other technological and/or pharmacokinetic advantages, to improve its encapsulation in liposomes, potentially driving its further body distribution and cellular uptake. Experimental data confirmed that a lipophilic derivative of LHRH was efficiently incorporated in various liposomal systems, differing in lipid composition and surface charge, and obtained using different methods of production. Incubation of liposomes, loaded with a fluorescent derivative of the LHRH prodrug, with NCTC keratinocytes or Caco-2 cell cultures showed that the carriers can be rapidly internalized. Conversely, the internalization of the free prodrug occurred only at very high concentrations.

Lipid-Based Drug Delivery Systems in Cancer Therapy: What Is Available and What Is Yet to Come

“…In addition, SUVs that are only 0.26 6 0.01 mm in size were able to encapsulate 54.8 6 1.1% of the same complex (Maestrelli et al, 2006). A similar trend was also observed in liposomes encapsulating luteinizing hormone-releasing hormone (Pignatello et al, 2015). MLVs with a size larger than 2 mm were able to encapsulate 78.8-81.4% of luteinizing hormone-releasing hormone, whereas LUVs that were 241-269.5 nm in size could incorporate 66.7-77.9% of the same hormone (Pignatello et al, 2015).…”

“…In addition, lamellarity also determines the stability, drug loading capacity, as well as drug release properties of liposomes (Maestrelli et al, 2006;Wacker, 2013;Pignatello et al, 2015). A higher degree of lamellarity often gives a more stable liposome vesicle compared with a vesicle with fewer layers (Tayebi et al, 2012).…”

“…Lamellarity can also affect the encapsulation efficiency of liposomes (Maestrelli et al, 2006;Pignatello et al, 2015). As MLVs contain multiple phospholipid bilayers, they are generally bigger than LUVs and SUVs (Vemuri and Rhodes, 1995).…”

Critical Parameters for Particle-Based Pulmonary Delivery of Chemotherapeutics

“…The lipid-based carriers employed in PPDS design could be generally categorized to liposomes, solid lipid nanoparticles (SLNs), and nano-sized lipid carriers (NLCs). Liposomal formulations with compositions similar to lung surfactants could serve as potential carriers for pulmonary delivery of therapeutics, owing to their low local irritation to the lung parenchyma, high biodegradability, sustained release behavior, (3)(4)(5)(6)(7)(8)(9)(10) controllable surface charge, (11)(12)(13)(14) as well as capability of encapsulating hydrophilic, (15)(16)(17) amphiphilic, (15) or hydrophobic (15,(18)(19)(20)(21) compounds. Liposomes could also be produced in both dry powder (22) and liquid suspension (23)(24)(25) forms based on the pulmonary delivery setup.…”

Lipid-engineered nanotherapeutics for cancer management

“…Pignatello et al showed that 2 mm or large-sized MLVs had encapsulation efficiency of luteinizing hormone of around 78.8%–81.4%, whereas LUVs in the 241.0–269.5 nm size range demonstrated 66.7%–77.9% entrapment efficiency of the same hormone. ( Pignatello et al, 2016 ).…”