Search

Siekiant pagreitinti 5-aminolevulino rūgšties (5-ALA) skvarbą į (pro) odą ir sudaryti terapines fotodinaminiam gydymui tinkamas jos koncentracijas, įvertinta 5-ALA ir naujo provaisto skvarba į (pro) odą iš įvairių vietinio poveikio vaisto formų. Atlikta naujo provaisto 2-(dimetilamino)-etil-5-amino-4-oksopentanoato (DMAE-ALA) sintezė, ištirtos jo charakteristikos. Nustatytas susintetinto provaisto stabilumas įvairių pH verčių buferiniuose vandeniniuose tirpaluose ir odos esterazių poveikyje, įrodytas provaisto tinkamumas pernašai į (pro) odą. Atlikti 5-ALA ir du teigiamus krūvius vaisto formoje įgaunančio provaisto jontoforetinės ir pasyvios pernašos iš buferinių tirpalų ir celiuliozinės bei polivinilkarboksilinės kilmės polimerinių gelių į (pro) odą tyrimai in vitro. Patvirtintas reikšmingas skatinamas jontoforezės poveikis krūvinių molekulių pernašai į (pro) odą ir krūvio dydžio reikšmė elektros srovės skatinamos pernašos greičiui. Ištirta vaisto formų, pagamintų iš polivilinkarboksilinės kilmės ir celiuliozės polimerų, kokybė ir jų pasyvioji bei jontoforetinė pernaša. Įrodyta, kad provaisto įterpimui naudojant celiuliozės polimerų pagrindu pagamintus gelius, pasiekiama didžiausia 5-ALA pernaša. Nustatyta, kad du krūvius turintis 5-ALA provaistas į (pro) odą skverbėsi geriau negu vieną krūvį įgaunantys arba elektriškai neutralūs 5-ALA dariniai. Sudarytos rekomendacijos, skirtos pasiekti didžiausiai 5-ALA pernašai į (pro) odą. Passive and iontophoretic delivery of 5-aminolevulinic acid and newly synthesized prodrug into (through) skin from various topical formulations was evaluated, while trying to accelerate the penetration of 5-ALA and its derivative into (through) skin and to generate the therapeutic concentration suitable for photodynamic therapy. A new prodrug 2-(dimethylamino)-ethyl-5-amino-4-oxopentanoate (DMAE-ALA) was synthesized, its characteristics have been evaluated. Stability of the prodrug in aqueous solutions of various pH values and at exposure with skin esterases (dermal and epidermal stability) has been evaluated. Suitability of the prodrug for topical delivery was confirmed. Studies for the evaluation of 5-ALA and DMAE-ALA passive and active delivery from cutaneous solutions, cellulose and polyvinyl carboxy polymer gels into (through) skin in vitro have been performed. Significant effect of iontophoresis on delivery of charged molecules into (through) skin as well as the significance of the charge of the molecule on the delivery rate has been confirmed. It has been shown that the insertion of the prodrug into cellulose-based polymer gels produces the highest amount of 5-ALA delivered into (through) skin. It was determined that the two-charged prodrug DMAE-ALA penetrated into (through) the skin more efficiently than single-charged or electrically neutral 5-ALA derivatives. Recommendations for achieving most efficient 5-ALA delivery into (through) the skin have been composed.

Passive and iontophoretic delivery of 5-aminolevulinic acid and newly synthesized prodrug into (through) skin from various topical formulations was evaluated, while trying to accelerate the penetration of 5-ALA and its derivative into (through) skin and to generate the therapeutic concentration suitable for photodynamic therapy. A new prodrug 2-(dimethylamino)-ethyl-5-amino-4-oxopentanoate (DMAE-ALA) was synthesized, its characteristics have been evaluated. Stability of the prodrug in aqueous solutions of various pH values and at exposure with skin esterases (dermal and epidermal stability) has been evaluated. Suitability of the prodrug for topical delivery was confirmed. Studies for the evaluation of 5-ALA and DMAE-ALA passive and active delivery from cutaneous solutions, cellulose and polyvinyl carboxy polymer gels into (through) skin in vitro have been performed. Significant effect of iontophoresis on delivery of charged molecules into (through) skin as well as the significance of the charge of the molecule on the delivery rate has been confirmed. It has been shown that the insertion of the prodrug into cellulose-based polymer gels produces the highest amount of 5-ALA delivered into (through) skin. It was determined that the two-charged prodrug DMAE-ALA penetrated into (through) the skin more efficiently than single-charged or electrically neutral 5-ALA derivatives. Recommendations for achieving most efficient 5-ALA delivery into (through) the skin have been composed.